What is beta lactam allergy

I Sanchez-Machin, R G P Poza, J Iglesias-Souto, V Iraola, V Matheu (2010)OralmiteanaphylaxisAllergy 65: 10. 1345-1347 Notes: Sanchez-Machin, I. Glez-Paloma Poza, R. Iglesias-Souto, J. Iraola, V. Matheu, V. V Matheu, Y Barrios, M R Arnau, V Navikas, S Issazadeh-Navikas (2010)SimilarresponseinmaleandfemaleB10.RIIImiceinamurinemodelofallergicairwayinflammationInflammation Research 59: 4. 263-269 Notes: Matheu, Victor Barrios, Ysamar Arnau, Maria-Rosa Navikas, Vaidrius Issazadeh-Navikas, Shohreh I Sanchez-Machin, C Moreno, R Gonzalez, J Iglesias-Souto, E Perez, V Matheu (2010)Safetyofa2-VisitClusterScheduleofVenomImmunotherapyinOutpatientsatRiskofLife-threateningAnaphylaxisJournal of Investigational Allergology and Clinical Immunology 20: 1.

91-92 Notes: Sanchez-Machin, I. Moreno, C. Gonzalez, R. Iglesias-Souto, J. Perez, E. Matheu, V. V Matheu, K Berggard, Y Barrios, M R Arnau, J M Zubeldia, M L Baeza, O Back, S Issazadeh-Navikas (2009)ImpactonallergicimmuneresponseaftertreatmentwithvitaminANutrition & Metabolism 6: Notes: Matheu, Victor Berggard, Karin Barrios, Yvelise Barrios, Ysamar Arnau, Maria-Rosa Zubeldia, Jose M. Baeza, Maria L. Back, Ove Issazadeh-Navikas, Shohreh A Navarro, C Colas, E Anton, J Conde, I Davila, M T Dordal, B Fernandez-Parra, M D Ibanez, M Lluch-Bernal, V Matheu, J Montoro, C Rondon, M C Sanchez, A Valero (2009)EpidemiologyofAllergicRhinitisinAllergyConsultationsinSpain:Alergologica-2005Journal of Investigational Allergology and Clinical Immunology 19: 7-13 Notes: Navarro, A.

Colas, C. Anton, E. Conde, J. Davila, I. Dordal, M. T. Fernandez-Parra, B. Ibanez, M. D. Lluch-Bernal, M. Matheu, V. Montoro, J. Rondon, C. Sanchez, M. C. Valero, A. xD;Suppl. 2 E Perez, R Gonzalez, J Martinez, J Iglesias, V Matheu (2009)DETEMIRINSULIN-INDUCEDANAPHYLAXISAnnals of Allergy Asthma & Immunology 102: 2. 174-175 Notes: Perez, Eva Gonzalez, Ruperto Martinez, Juan Iglesias, Javier Matheu, Victor R Gonzalez-Perez, P Poza-Guedes, V Matheu, I Sanchez-Machin, J Iglesias-Souto, E Rodriguez-Plata, J Garcia-Robaina (2008)PreliminarydataofselectedpopulationsensitizedtocheyletuseruditusJournal of Allergy and Clinical Immunology 121: 2.

Notes: Gonzalez-Perez, R. Poza-Guedes, P. Matheu, V. Sanchez-Machin, I. Iglesias-Souto, J. Rodriguez-Plata, E. Garcia-Robaina, J. xD;Suppl. 1 R Gonzalez-Perez, P Poza-Guedes, V Matheu, E Perez-Rodriguez, I S Machin, J Garcia-Robaina (2008)Cheyletuseruditus:AnovelindoorallergenAnnals of Allergy Asthma & Immunology 100: 1. A41-A41 Notes: Gonzalez-Perez, R. Poza-Guedes, P. Matheu, V. Perez-Rodriguez, E. Machin, I. Sanchez Garcia-Robaina, J. xD;Suppl. 1 V Matheu, E Perez, R Gonzalez, A Franco, J Garcia-Robaina, Y Barrios (2008)TcellactivationafterOmalizumabforinsulinallergyJournal of Allergy and Clinical Immunology 121: 2.

Notes: Matheu, V. Perez, E. Gonzalez, R. Franco, A. Garcia-Robaina, J. Barrios, Y. xD;Suppl. 1 E Perez-Rodriguez, R Gonzalez-Perez, P Poza, L Feliciano, B Lopez-Correcher, V Matheu (2008)Contactdermatitiscausedbylatanoprost-containingeyedropswithgoodtolerancetobimatoprosteyedropsContact Dermatitis 58: 6. 370-U8 Notes: Perez-Rodriguez, Eva Gonzalez-Perez, Ruperto Poza, Paloma Feliciano, Laura Lopez-Correcher, Beatriz Matheu, Victor E Perez-Rodriguez, R Gonzalez-Perez, J Martinez-Tadeo, P Poza-Guedes, E Rodriguez-Plata, V Matheu (2008)Anaphylaxisduetoanewinsulinanalogue:detemirAllergy 63: Notes: Perez-Rodriguez, E.

Gonzalez-Perez, R. Martinez-Tadeo, J. Poza-Guedes, P. Rodriguez-Plata, E. Matheu, V xD;Suppl. 88 V Matheu, A Franco, E Perez, M Hernandez, Y Barrios (2007)OmalizumabfordrugallergyJournal of Allergy and Clinical Immunology 120: 6. 1471-1472 Notes: Matheu, Victor Franco, Andres Perez, Eva Hernandez, Marta Barrios, Yvelise V Matheu, E Perez, R Gonzalez, P Poza, F de la Torre, I Sanchez-Machin, J C Garcia-Robaina (2007)Assessmentofanewbrandofdeterminantsforskintestinginalargegroupofpatientswithsuspectedbeta-lactamallergyJournal of Investigational Allergology and Clinical Immunology 17: 4.

257-260 Notes: Matheu, V. Perez, E. Gonzalez, R. Poza, P. de la Torre, F. Sanchez-Machin, I. Garcia-Robaina, J. C. V Matheu, Y Barrios, K Berggrd, M Baeza, J Zubeldia, O Back, S Issazadeh-Navikas (2007)InfluenceofretinoicacidinallergicinflammationAnnals of Allergy Asthma & Immunology 98: 1. A83-A83 Notes: Matheu, V. Barrios, Y. Berggrd, K. Baeza, M. Zubeldia, J. Back, O. Issazadeh-Navikas, S. xD;Suppl. 1 V Matheu, E Perez-Rodriguez, R Gonzalez-Perez, P Poza, I Sanchez-Machin, F de la Torre, J Garcia-Robaina (2007)Assessmentofanewbrandofdeterminantsforskintestinalargegroupofpatientswithasuspectofbeta-lactamallergyAllergy 62: 532-533 Notes: Matheu, V.

Perez-Rodriguez, E. Gonzalez-Perez, R. Poza, P. Sanchez-Machin, I. de la Torre, F. Garcia-Robaina, J. xD;Suppl. 83 I Sanchez-Machin, R Elena, M Lourdes, V Matheu, R Gonzalez-Perez, J Garcia-Robaina (2007)Hypersensitivitytolowmolecularweightheparinsandtoleranceofnon-fractionedheparinandfonclaparinuxAllergy 62: 526-526 Notes: Sanchez-Machin, I. Elena, R. Lourdes, M. Matheu, V. Gonzalez-Perez, R. Garcia-Robaina, J. xD;Suppl. 83

  • In the outpatient setting, numerous authorities prefer to reserve fluoroquinolones
    (Levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin) for patients with comorbid diseases/risk factors
  • In most cases, patients with pneumonias due to these organisms should be hospitalized

  • Levofloxacin, gatifloxacin, moxifloxacin, or gemifloxacin

  • Critically ill patients in areas with significant rates of high-level pneumococcal resistance and a suggestive sputum gram-stain should get vancomycin or a newer quinolone pending microbiologic diagnosis.

  • Piperacillin-tazobactam or ampicillin-sulbactam

  • Cefpodoxime, cefuroxime, high-dose amoxicillin, amoxicillin/clavulanate; or parenteral ceftriaxone followed by oral cefpodoxime

  • Cefotaxime, ceftriaxone, ampicillin/sulbactam, or high-dose ampicillin.
  • 2016 — 2019

    Imlay H, Krantz EM, Stohs Ej, Lan KF, Zier J, Kim HN, Rakita RM, Limaye AP, Wald A, Pergam SA, Liu C.

    Reported Beta Lactam and Other Antibiotic Allergies in Solid Organ and Hematopoietic Cell Transplant Recipients. Clinical Infectious Diseases 2019; Oct 17 doi: 10.1093/cid/ciz1025 PMID: 31621829 

    Chan JD, Bryson-Cahn C, Jain R, Lynch JB, Liu C. Does oral vancomycin prophylaxis during systemic antibiotic exposure prevent Clostridioides difficile infection relapses? Still in search of an answer.. Infection Control & Hospital Epidemiology 2019 Sep;40(9):1084-1086.

    doi: 10.1017/ice.2019.192 PMID: 31288875

    Krantz EM, Zier J, Stohs E, Ogimi C, Sweet A, Marquis S, Klaassen J, Pergam SA, Liu C. Antibiotic Prescribing and Respiratory Viral Testing for Acute Upper Respiratory Infections Among Adult Patients at an Ambulatory Cancer Middle. Clinical Infectious Disease 2019 May 16. pii: ciz409. doi: 10.1093/cid/ciz409. PMID: 31095276

    Stohs E, Chow VA, Liu C, Bourassa L, Miles-Jay A, Knight J, Sweet A, Storer BE, Mielcarek M, Pergam SA. Limited Utility of Outpatient Surveillance Blood Cultures in Hematopoietic Cell Transplant Recipients on High-Dose Steroids for Treatment of Acute Graft-versus-Host-Disease.

    Biol Blood Marrow Transplant 2019 Feb 1. doi: 10.1016/j.bbmt.2019.01.031. PMID: 30711778

    Liu C, Strnad L, Beekmann SE, Polgreen PM, Chambers H. Clinical Practice Variation Among Adult Infectious Diseases Physicians in the Management of Staphylococcus aureus Bacteremia. Clinical Infectious Diseases. 2019; Jan 2, PMID: 30601989 

    Chan A, Ammanuel SG, Chan AY, Oh T, Skrehot HC, Edwards CS, Kondapavulur S, Miller CA, Nichols A, Liu C, Dhall SS, Clark AJ, Chou D, Ames CP, Mummaneni P. Chlorhexidine showers are associated with a reduction in surgical site infection following nonfusion spine surgeries: an analysis of 4,293 consecutive surgeries. Neurosurgery 2018; Dec 22 PMID 30590721 

    Ogimi C, Krantz EM, Golob JL, Waghmare A, Liu C, Leisenring WM, Woodard CR, Marquis S, Kuypers JM, Jerome KR, Pergam SA, Fredricks DN, Sorror ML, Englund JA, Boeckh M.

    Antibiotic Exposure Prior to Respiratory Viral Infection Is Associated with Progression to Lower Respiratory Tract Disease in Allogeneic Hematopoietic Cell Transplant Recipients. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2018. PMID: 29777867

    Stohs EJ, MacAllister T, Pergam SA, Krantz EM, Jain R, Sweet A, Liu C. Unintended Consequences of Pretransplant Vancomycin-Resistant Enterococcus Screening on Antimicrobial Stewardship Among Allogeneic Hematopoietic Cell Transplant Recipients. Infection Control and Hospital Epidemiology. 2018; 39(6):730-733. PMID: 29589825

    Vermandere M, Aertgeerts B, Agoritsas T, Liu C, Burgers J, Merglen A, Okwen P, Lytvyn L, Chua S, Vandvik P, Guyatt G, Beltran-Arroyave C, Lavergne V, Speeckhaert R, Steen F, Arteaga V, Sender R, McLeod S, Sun X, Wang W, Siemieniuk R.

    Antibiotics for uncomplicated skin abscesses: a clinical practice guideline. BMJ 2018; 360: k243 PMID: 29437651

    MacAllister T, Stohs E, Liu C, Amanda Phipps A, Pergam SA. Ten Year Trends in Incidence of Vancomycin-resistant EnterococcusAmong Allogeneic Hematopoietic Cell Transplant Recipients. Journal of Infection 2018; May 7 PMID:29746941

    Trang TP, Whalen M, Hilts-Horeczko A, Doernberg SB, Liu C. Comparative effectiveness of aerosolized versus oral ribavirin for the treatment of respiratory syncytial virus infections: A single-center retrospective cohort study and review of the literature. Transplant Infectious Disease : an official journal of the Transplantation Society.

    2018; 20(2):e12844. PMID: 29360277

    Baxi SM, Robinson ML, Grill MF, Schwartz BS, Doernberg SB, Liu C. Clinical Characteristics and Outcomes Among Individuals With Spinal Implant Infections: A Descriptive Study. Open Forum Infectious Diseases. 2016; 3(3):ofw177. PMID: 27704027 PMCID: PMC5047418



    VMatheu


    2006 — 2010

    Liu C, Schwartz BS, Vallabhaneni S, Nixon M, Chin-Hong PV, Miller SA, Chiu C, Damon L, Drew WL.

    Pandemic (H1N1) 2009 infection in patients with hematologic malignancy. Emerging Infectious Diseases. 2010; 16(12):1910-7. PMID: 21122221 PMCID: PMC3294592

    Krasik EF, Liu C, Visvesvara GS. A 53-year-old lady with rapidly progressive altered mental status and ataxia. Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America. 2010; 51(5):575-6, 629-30. PMID: 20684678

    Kumar D, Michaels MG, Morris MI, Green M, Avery RK, Liu C, Danziger-Isakov L, Stosor V, Estabrook M, Gantt S, Marr KA, Martin S, Silveira FP, Razonable RR, Allen UD, Levi ME, Lyon GM, Bell LE, Huprikar S, Patel G, Gregg KS, Pursell K, Helmersen D, Julian KG, Shiley K, Bono B, Dharnidharka VR, Alavi G, Kalpoe JS, Shoham S, Reid GE, Humar A.

    Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. The Lancet. Infectious Diseases. 2010; 10(8):521-6. NIHMSID: NIHMS267572 PMID: 20620116 PMCID: PMC3045703

    Nadarajah R, Post LR, Liu C, Miller SA, Sahm DF, Brooks GF. Detection of vancomycin-intermediate Staphylococcus aureus with the updated Trek-Sensititre System and the MicroScan System. Comparison with results from the conventional Etest and CLSI standardized MIC methods. American Journal of Clinical Pathology. 2010; 133(6):844-8. PMID: 20472841

    Elicker BM, Schwartz BS, Liu C, Chen EC, Miller SA, Chiu CY, Webb WR.

    Thoracic CT findings of novel influenza A (H1N1) infection in immunocompromised patients. Emergency Radiology. 2010; 17(4):299-307. PMID: 20111882 PMCID: PMC2880241

    Liu C, Graber CJ, Karr M, Diep BA, Basuino L, Schwartz BS, Enright MC, O’Hanlon SJ, Thomas JC, Perdreau-Remington F, Gordon S, Gunthorpe H, Jacobs R, Jensen P, Leoung G, Rumack JS, Chambers HF. A population-based study of the incidence and molecular epidemiology of methicillin-resistant Staphylococcus aureus disease in San Francisco, 2004-2005. Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America. 2008; 46(11):1637-46. PMID: 18433335

    Liu C, Christie LJ, Neely J, Gandhi M, Jacobs RA, Bollen A, Glaser CA.

    Tuberculous meningoencephalitis in a pregnant lady presenting 7 years after removal of a cerebral granuloma. European Journal of Clinical Microbiology & Infectious Diseases : official publication of the European Society of Clinical Microbiology. 2008; 27(3):233-6. PMID: 18034270


    2011 — 2015

    Lee S, Prasad P, Lin M, Garritson S, Nichols A, Liu C. Ertapenem Prophylaxis Associated With an Increased Risk of Clostridium difficile Infection Among Surgical Patients. Infection Control and Hospital Epidemiology. 2015; 36(11):1351-4. PMID: 26278576

    Baxi SM, Liu C. Mortality and timing of surgery for prosthetic valve endocarditis. JAMA Internal Medicine.

    2014; 174(3):480. PMID: 24590095

    Liu C, Kakis A, Nichols A, Ries MD, Vail TP, Bozic KJ. Targeted use of vancomycin as perioperative prophylaxis reduces periprosthetic joint infection in revision TKA. Clinical Orthopaedics and Related Research. 2014; 472(1):227-31. PMID: 23645338 PMCID: PMC3889430

    Mistry RD, Shapiro DJ, Goyal MK, Zaoutis TE, Gerber JS, Liu C, Hersh AL. Clinical management of skin and soft tissue infections in the U.S. Emergency Departments. The Western Journal of Emergency Medicine. 2014; 15(4):491-8. PMID: 25035757 PMCID: PMC4100857

    Liu C. Editorial commentary: a quality-of-care bundle for treatment of Staphylococcus aureus bacteremia: ready for prime time?

    Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America. 2013; 57(9):1234-6. PMID: 23929890

    Abdul-Jabbar A, Berven SH, Hu SS, Chou D, Mummaneni PV, Takemoto S, Ames C, Deviren V, Tay B, Weinstein P, Burch S, Liu C. Surgical site infections in spine surgery: identification of microbiologic and surgical characteristics in 239 cases. Spine. 2013; 38(22):E1425-31. PMID: 23873240

    Chow FC, Marson A, Liu C. Successful medical management of a Nocardia farcinica multiloculated pontine abscess. BMJ Case Reports. 2013; 2013. PMID: 24311420 PMCID: PMC3863074

    Tehrani DM, Russell D, Brown J, Boynton-Delahanty K, Quan K, Gibbs L, Braddock G, Zaroda T, Koopman M, Thompson D, Nichols A, Cui E, Liu C, Cohen S, Rubin Z, Pegues D, Torriani F, Datta R, Huang SS.

    Discord among performance measures for central line-associated bloodstream infection. Infection Control and Hospital Epidemiology. 2013; 34(2):176-83. PMID: 23295564

    Drew WL, Liu C. Repopulation of ganciclovir-resistant cytomegalovirus by wild-type virus. Clinical Transplantation. 2012; 26(6):949-52. PMID: 22774759

    Naidus E, Damon L, Schwartz BS, Breed C, Liu C. Experience with use of Zostavax(®) in patients with hematologic malignancy and hematopoietic cell transplant recipients. American Journal of Hematology. 2012; 87(1):123-5.

    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF.

    Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America. 2011; 52(3):285-92. PMID: 21217178

    Liu C.

    What is beta lactam allergy

    The bundled approach to MRSA surgical site infection prevention: is the whole greater than the sum of its parts?: comment on "Sustained reduction in methicillin-resistant Staphylococcus aureus wound infections after cardiothoracic surgery". Archives of Internal Medicine. 2011; 171(1):73-4. PMID: 21220664

    Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE, J Rybak M, Talan DA, Chambers HF. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.

    Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America. 2011; 52(3):e18-55. PMID: 21208910


    2005 and prior

    Eguia JM, Liu C, Moore M, Wrone EM, Pont J, Gerberding JL, Chambers HF. Low colonization prevalence of Staphylococcus aureus with reduced vancomycin susceptibility among patients undergoing hemodialysis in the San Francisco Bay area. Clinical Infectious Diseases : an official publication of the Infectious Diseases Society of America.

    2005; 40(11):1617-24. PMID: 15889359

    Liu C, Waters DD. Chlamydia pneumoniae and atherosclerosis: from Koch postulates to clinical trials. Progress in Cardiovascular Diseases. 2005; 47(4):230-9. PMID: 15991152

    Pham MX, Whooley MA, Evans GT Jr, Liu C, Emadi H, Tong W, Murphy MC, Fleischmann KE. Prognostic worth of low-level cardiac troponin-I elevations in patients without definite acute coronary syndromes.

    American heart journal. 2004; 148(5):776-82. PMID: 15523306 

    Liu C, Chambers HF. Staphylococcus aureus with heterogeneous resistance to vancomycin: epidemiology, clinical significance, and critical assessment of diagnostic methods. Antimicrobial Agents and Chemotherapy. 2003; 47(10):3040-5. PMID: 14506006 PMCID: PMC201119

    Jenkins DE, Redman RL, Lam EM, Liu C, Lin I, Arvin AM. Interleukin (IL)-10, IL-12, and interferon-gamma production in primary and memory immune responses to varicella-zoster virus. The Journal of infectious diseases. 1998; 178(4):940-8. PMID: 9806019 

    Redman RL, Nader S, Zerboni L, Liu C, Wong RM, Brown BW, Arvin AM.

    Early reconstitution of immunity and decreased severity of herpes zoster in bone marrow transplant recipients immunized with inactivated varicella vaccine. The Journal of Infectious Diseases. 1997; 17

    Prevalence of reported drug allergy and its impact on Beta lactam use with financial and health implications

    Abirami Murugesh-Warre1,2#, Ranu Malhin1,3#, Yogini Jani1, Christopher Corrigan4, David Walker1, Harsha Kariyawasam1 and Joanna Lukawska1,4*

    1University College London Hospitals, 235 Euston Rd, Bloomsbury, London NW1 2BU, UK

    2Whittington Hospital NHS Believe, Magdala Ave, London N19 5NF, UK

    3McMaster Children’s Hospital, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada

    4King’s College London, Guy’s Hospital, London SE1 9RT, UK

    *Address for Correspondence: Joanna Lukawska, University College London Hospitals, 235 Euston Rd, Bloomsbury, London NW1 2BU, UK, Tel: +447886596340; Email: [email protected]

    #Joint first Author: Abirami Murugesh-Warren, University College London Hospitals, 235 Euston Rd, Bloomsbury, London NW1 2BU, UK, Ranu Malhi, McMaster Children’s Hospital, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada

    Dates:Submitted: 01 August 2017; Approved: 21 August 2017; Published: 22 August 2017

    How to cite this article: Warren AM, Malhi R, Jani Y, Corrigan C, Walker D, et al.

    Prevalence of reported drug allergy and its impact on Beta lactam use with financial and health implications. Arch Asthma Allergy Immunol. 2017; 1: 028-035. DOI: 10.29328/journal.haard.1001004

    Copyright: © 2017 Warren AM, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Keywords: Penicillin; Beta lactams; Allergy; Antibiotic; Cost; Readmission; Self-reported; Drug allergy

    Background:While recognition and documentation of true drug allergy is critically significant, most physicians acknowledge that its prevalence is likely overestimated, often on the basis of historical, sometimes anecdotal evidence.

    Correct or not, once applied, drug allergy labels may result in altered, potentially inferior therapy, increased costs and prolonged hospitalisation.

    Objective:Estimate the point prevalence, accuracy and symptomatology of self-reported drug allergy in a typical, large NHS Acute Believe adult inpatient population. In the subset with penicillin allergy (PA), estimate additional management costs from the use of alternative antibiotics and readmission rates in the previous 5 years.

    Methods:Data on self-reported drug allergies were extracted from 440 adult inpatient prescription charts over a 4 month period.

    Where penicillin allergy (PA) was reported, alternative antibiotic regimens were recorded and their additional costs calculated. Hospital electronic records were used to assess readmission rates of PA patients.

    Results:194/440 inpatients (44.5%) reported at least one drug allergy. Antibiotic allergy was most commonly reported (51%), followed by analgesic (23%) and antiemetic (12%) allergy. PA accounted for 76% of reported antibiotic allergy. The commonest reported symptoms were cutaneous (42%) and gastrointestinal (18%). Where antibiotic therapy was required for patients with PA to manage acute infections, Ciprofloxacin, Clarithromycin, Teicoplanin, Clindamycin and Cefuroxime were the most commonly employed alternatives.

    Extrapolation of these figures to include the entire Believe inpatient population suggested that the use of alternative antibiotics in PA patients incurred additional annual expenditure of £268,000. Further, 87% of PA patients had been admitted more than once in the preceding 5 years, with 74% requiring further courses of antibiotics during these admissions.

    Conclusion:Self-reported drug allergy, and in specific PA, is common in hospital inpatient populations and, in addition to the potentially unnecessary hazards to individual patients resulting from the use of alternative antibiotics, results in a considerable additional financial burden to the healthcare system.

    This problem could be eliminated by the provision of a nationwide and equitable tertiary Allergy service.

    Drug allergy (DA) and its adverse effects own been well studied in humans [1-8], despite this an precise assessment of the prevalence and incidence of true drug allergy remains unknown, due in part to the challenges of the resource intense testing procedures [9]. Despite this uncertainty, it is clear that the true prevalence is likely to be much lower than that reported by patients [10].

    In routine clinical practice, and especially when compiling medical records, distinction of the authenticity of adverse drug reactions (ADRs) is of little practical importance; it is assumed that every drugs listed in the Drug Allergy section of a prescription chart are drugs that the patient’s doctors and pharmacists believe may own significant risk attached to them and are generally avoided.

    In contrast, this may be extremely problematic for the prescriber, particularly in cases of self-reported penicillin allergy (PA) in patients presenting with severe infections. Penicillin is narrow spectrum, well tolerated and inexpensive; consequently it is the most commonly prescribed antibiotic in secondary care [11]. The problem of self-reported PA is compounded by the fact that in practice, it is typically extended to include every betalactam (BL) drugs because of their potential for cross reactivity [12]. This is a serious concern as BL antibiotics are considered to be first-line empirical treatment for numerous life-threatening infections, such as bacterial meningitis [13], sepsis and septic shock [14], intra-abdominal infections [15], hospital-acquired, ventilator associated pneumonia [16], diabetic foot infections [17], and skin and soft tissue infections [18].

    The non-beta lactam (NBL) antibiotic therapy options that remain for patients labelled with PA include aminoglycosides, fluoroquinolones, tigecycline, or trimethoprim/sulphamethoxazole.

    Unfortunately, their use has been associated with higher treatment failure rates [19], more significant unwanted effects, a greater incidence of Clostridium difficile, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus species super-infections, antibiotic resistance [13,14] and longer lengths of stay compared with those without PA [9].

    The pharmacoeconomic impact of PA is also not insignificant. Picard and colleagues estimated that patients labelled as having PA carried an individual additional cost of more than $326 per patient per admission [20].

    In the UK, the cost of NBL antibiotics may be 1.82-2.58 fold higher than first-line antibiotics when used in patients with PA [21].

    We designed a study to determine the point prevalence, symptomatology and accuracy of self-reported DA in secondary care.

    We then focused on PA. We aimed to determine how numerous of our sample of patients were eligible for BL therapy as ‘first line’ treatment according to local and national guidelines, and how this treatment was modified by a label of PA.

    Finally, we estimated the incremental costs incurred through use of these alternative regimes during the current admission and thus the potential savings from ‘unlabelling’ these patients. We further examined the recurrent admission rates of these PA labelled patients to extrapolate potential savings over a 5-year period.

    We undertook a cross-sectional study of 440 prescription charts for adult patients admitted to the surgical and medical wards of a large NHS Acute Believe (1,093 inpatient beds) over a 4-month period between November 2014 and February 2015. Patients were questioned on admission using a standard proforma. The presence or absence of DA, the medications listed and the signs and symptoms of DA appearing in the ‘DA’ section of the prescription were recorded.

    Every DA listed in the prescription was confirmed with the patient.

    We enquired about the accuracy of the record with the patient and whether DA was confirmed by an allergist. Where PA was reported, alternative antibiotics used during the present admission were documented, if required. In order to estimate the cost implications of prescribing alternative antibiotics to patients with self-reported PA, we studied a subset of 27 patients with a range of diseases (community acquired pneumonia, hospital acquired pneumonia, sepsis of unknown origin, infective exacerbation of COPD, neutropaenia, abdominal sepsis, skin infection and osteomyelitis) in whom therapy with BL would be considered ‘first line’ according to local hospital guidelines, but required alternatives due to the documented PA (Table 1).

    Prices for each medicine were derived primarily from the Drug Tariff available at the time of the analysis. Where products were not listed in the Drug Tariff, list prices were derived from the British National Formulary (Table 2) [22,23]. This was the basic drug tariff and did not include additional costs of personnel and therapeutic monitoring required for some of the BL alternatives. We then compared these costs with the theoretical costs of istering BL antibiotic therapy as per local and national guidelines. For this we used the prices of standard intravenous therapy (Table 2), reasoning that this would most likely own been employed for these acute, severe systemic infections.

    The differences between the costs were then summed to compute the additional daily cost. Costing analysis was conducted by 2 researchers independently.

    Table 1: cost of alternative antibiotics versus 1st line treatment for 8 common conditions with BL as 1st line treatment.
    Condition No of pt treated* 1st line Abx Total daily cost 1st line (£) ** Actual entire daily costs (£) Ù Estimated entire daily additional cost (£)ÙÙ Fold increase in cost ^
    Community acquired pneumonia 7 Cefuroxime 106.05 149.95 43.90 1.41
    Hospital acquired pneumonia 5 Amoxicillin + clarithromycin 102.75 143.16 40.41 1.39
    Sepsis of unknown origin 5 Cefuroxime 75.75 213.01 137.26 2.81
    COPD infective exacerbation 3 Amoxicillin 4.95 48.32 43.37 9.76
    Neutropaenic sepsis 2 Tazocin + gentamicin 72.58 137.16 64.58 1.89
    Abdominal sepsis 2 Cefuroxime 30.30 42.65 12.35 1.41
    Skin infection 2 IV flucloxacillin 66.80 38.57 -28.23 0.58
    Osteomyelitis 1 IV flucloxacillin + PO sodium fusidate 37 19.67 -17.33 0.59
     Total patients 27  Total savings per day £296.31
    *only includes PA patients who suffered from a condition for which a beta-lactam antibiotic was 1st line treatment.
    **total daily cost of treating every patients with the specific condition according to 1st line antibiotic regime (IV costs used to provide conservative price difference).
    Ù Entire daily cost of alternative antibiotic regime prescribed in the believe if treating every patients with the specific condition.

    ÙÙ Difference between entire daily costs of preferred regime (involving BL) subtracted from alternative antibiotic entire daily costs.
    ^ Calculation= (actual daily cost per pt/total cost 1st line per pt).

    Table 2: cost of antibiotics used for calculations [22,23].
    Class of Antibiotic Antibiotic Cost per patient per day (£)
     BL Antibiotics Cefuroxime 15.15
    Amoxicillin 1.65
    Tazocin 60.68
    Ceftriaxone 19.18
    Co-amoxiclav 3.18
    Flucloxacillin (IV) 33.40
    Non-BL Antibiotics
    Chloramphenicol 5.56
    Fluoroquinolones Ciprofloxacin 39.58
    Macrolides Clarithromycin 18.90
    Glycopeptides Teicoplanin 7.32
    Vancomycin 25.00
    Lincosamide Clindamycin 12.35
    Aminoglycoside Gentamicin 5.95
    Fusidane Sodium fusidate 3.60
    Trimethoprim 0.14

    The hospital’s Electronic Record System was used to review the numbers of previous admissions in the preceding 2 and 5 year periods prior to the index period for patients with self-reported PA.

    The electronic ‘Discharge Summary’ was used to assess how numerous of these admissions required antibiotics and what antibiotic alternatives were used.

    A entire of 440 inpatient prescription charts were reviewed. 194 (44.5%) of the inpatients, of whom 141 were female, had at least one DA recorded in the DA prescription box of their chart while 16% reported two or more. Only 2 patients had been investigated for drug allergy in an allergy clinic. Their DA diagnoses were confirmed through skin testing and challenges. Drug prescription charts reviewed were generally precise (99%): one patient reported additional DA to omeprazole that had not been documented, while another denied documented clarithromycin allergy.

    Antibiotic allergy was the commonest self-reported DA, accounting for 51% of the entire reported, while PA accounted for 17.5% (n=77) of the entire reports and 76% of the antibiotic allergy reports.

    Analgesic and anti-emetic allergy accounted for a further 23% and 12% of the entire reports respectively (Figure 1). Reported manifestations of DA reactions were cutaneous (41%), gastrointestinal (19%), neurological (10%), respiratory (4%) and other miscellaneous (6%). Ten percent of reports were of systemic anaphylaxis. A further 10% were considered non-immunologically mediated (e.g. gastrointestinal bleeds with NSAIDs). Self-reported DA was commoner in older patients, with 69% of the entire reported by patients aged >55 years.

    Figure 1: Classes of Drugs Causing Allergies.

    The range of self-reported symptoms of the patients with PA is shown in figure 2.

    Interestingly, 44% of these patients were uncertain or ignorant of the drug-induced symptoms which had resulted in their being labelled as having PA.

    Figure 2: Drug reactions as reported by penicillin allergic patients.

    Of the 77 self-reported PA patients in our cross-sectional survey, 36 (47%) required antibiotic therapy during the current (index) admission, while for 27 patients (35%) we judged that therapy with BL antibiotics would own been considered ‘first line’ therapy according to national and local guidelines.

    For such patients, Ciprofloxacin (16%) was the most commonly used alternative, followed by Clarithromycin (11%), Teicoplanin (8%) and Clindamycin (5%). Cephalosporins were generally avoided in patients with a PA label and used in only in 6.35% (Cefuroxime 5% and Ceftriaxone 1.35%).

    Cost calculations suggested an additional daily absolute local pharmacy tariff of £296.31 for the 27 patients (6.1% of the study population) who were labelled with PA and who would otherwise own been treated with BL as ‘first line’ therapy as per guidelines (Tables 1 and 2).

    If this is extrapolated theoretically to include the entire inpatient population of the Believe (1093 patients, assuming that every beds are occupied), the additional estimated cost of alternative antibiotics for this hospital alone is £734.26 per day, £22,334 per month and £268,000 per year.

    A review of the historical electronic records of patients with a self-reported, documented penicillin allergy revealed that 73% and 87% of PA patients identified during the study were admitted more than once in the preceding 2 and 5 year periods, equating to 332 and 465 entire readmissions respectively. Seventy-four percent of the PA patients required antibiotics at least once during their readmissions (Table 3).

    Again, Ciprofloxacin was the most commonly used antibiotic (14%), followed by Clarithromycin (13%), Teicoplanin (7%), Clindamycin (5%), Doxycycline (5%) and Cefuroxime (5%). We were unable to establish from electronic records the type of antibiotic used in 11% of the cases.

    Table 3: Admission rates for penicillin allergic patients.
    2 years 5 years
    Total no. of admissions 332 465
    Average no.

    of admissions per patient

    4.31 6.04
    No. of patients requiring readmission (%) 56 (73) 67 (87)
    Total admissions requiring antibiotics 174
    No. of patients requiring antibiotics (%) 57 (74)

    Self-reported DA was a common finding amongst our medical and surgical adult inpatients. We found that staggeringly 44.5% reported being allergic to at least one medication [24,25].

    Although there appears to be a surprising paucity of studies on this subject matter, others own reported it to be in the range of 7% to 39% [24-26]. The discrepancy between our results and others may be related to the fact that up to 25% of drug reactions although reported by the patients, remain unrecorded in prescription charts and medical records [27].

    The prevalence of reported PA has been estimated at 8%-16% [28-32]. Of the inpatient population studied here, 17.5% had a PA recorded in their drug chart.

    While failing to ascertain, document and act on drug allergies may be a threat to the health care of individual patients, so may the untrue assumption that they exist.

    DA diagnosis is hard to establish based on clinical history alone [33,34], hence most patients with a label of DA would not ordinarily get that drug again. This underlines the essential role of formal allergy diagnosis in an allergy clinic; to confirm and characterize DA when it exists and to eliminate the label when it does not. This is particularly pertinent in the case of PA, as penicillin/BL substitution may result in poorer clinical efficacy and potentially serious unwanted effects, such as colonisation with Clostridium difficile and promotion of antibiotic resistance [9,19,24,25].

    Furthermore, following assessment by an allergist, 80-90% of patients with a label of PA are demonstrated to be capable to tolerate penicillins [35]. Penicillin skin testing is safe and its negative predictive worth is high. In large-scale studies, only 1-3% of patients with negative skin test responses had mild and self-limiting reactions on being challenged with the drug [28]. It is of course not without a cost, however, Macy and Contreras estimated that the cost of extended inpatient stay alone is 9.5 times as much as penicillin allergy testing would cost [9].

    When prescribing antibiotics physicians’ choice is based on several factors: underlying condition, local and national guidelines, personal experience, antibiotic sensitivity; antibiotic allergy is only one of the factors consider.

    In the present study, BL antibiotics were the standard of care for 36% of patients labelled with PA, while quinolones, macrolides, glycopeptide and lincosamide antibiotics are the most commonly prescribed alternative antibiotic classes in those with presumed PA.

    This is in keeping with other studies demonstrating that quinolones, carbapenems and clindamycin are generally employed instead of penicillin [36,37].

    Our ‘snapshot’, cross-sectional data suggests that the approximate additional cost of treating penicillin allergic patients in this typical, acute Believe is £268,000 per year. This is likely a minimum estimate, as this figure does not take into account the possible costs of treating unwanted effects of NBL antibiotics or cost of therapeutic drug monitoring required for several NBLs. Actual drug costs are, however, arguably only the tip of the iceberg. The mean duration of hospital admission for patients labelled with PA has been reported as 0.6 days longer than for control subjects [9].

    Macy and Contreras estimated $64.6 million saving over a 3-year study period by virtue of shortening the hospital stay [9].

    The problem is compounded with each readmission requiring antibiotics. A significant proportion of hospital inpatients suffer from chronic conditions and require one or more admissions in any calendar year. Remarkably, in our present study 87% of PA patients had at least one other admission in the previous 5 years and antibiotic treatment was required at least once for over 74% of these, suggesting that overall costs over time for PA patients are much greater.

    All of this data appears to underline the need for a concerted, global approach to the management of DA.

    It seems likely that the costs of providing a comprehensive allergy service would be more than offset by savings accrued through cheaper drugs and shorter hospital stays, especially given the readmission rates of most of our PA patients.

    It seems inexplicable, therefore, that Allergy as a specialty, and in spite of the previous Parliamentary inquiry, remains “the unmet need” within the NHS [38]. Lack of allergy specialists is a global problem: 66% of Canadian physicians believe that shortage of allergists is a barrier to effective assessment of DA [20].

    Only 1% of our inpatients with self-reported DA were reviewed by an allergist. Picard and colleagues made a excellent case for having allergist on staff in every Canadian teaching hospital [20]. Canada has similar number of physicians per capita to the UK (2.6 vs 2.8 per 1000 people) [39]. There are 188 allergists and 35 allergy trainees, serving the population of 35 million Canadians [40]. In the UK, there are 35 Allergy consultants and 8 allergy trainees serving the population of 65 million.

    An allergist in most, if not every tertiary referral centre, would start to address the unmet need in the specialty. However, considering that there are 154 acute trusts, it is clear that at present and in the foreseeable future this remains unachievable.

    DA will continue to be a relevant issue for medical practitioners. We are using more medications including biologicals, which are immunogenic by design, and we are living longer, giving individuals more time to acquire more ADRs.

    We therefore need specialists who can competently deal with this problem. In spite of austerity measures and budgetary cuts, we should invest in allergy, an investment that is likely to bring quick and irrefutable dividends.

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      Comment: Study of 115 patients with staph or strep bacteremia using FDG-PET/CT technology looking for metastatic infections found foci in 84 of 115 (73%) patients: endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. Signs or symptoms directing a diagnostic work-up were only present in 41%, suggesting that additional studies may be helpful even in absence of specific findings: for example in this study PET was the first to detect problems in 30%.

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    • Dhand A, Bayer AS, Pogliano J, et al. Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis.

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      Comment: Authors capable to clear persistent bacteremia in 7 pts with combination of daptomycin and oxacillin or nafcillin (2g IV q4h) in seven patients.

      What is beta lactam allergy

      Mechanism not entirely clear but may be due to enhanced membrane binding of daptomycin in the presence of the beta-lactam.

    • British National Formulary. [Internet]. medicinescomplete.com. [Cited October 5, 2016]. Ref.: https://goo.gl/GmWRHa
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    • DiNubile MJ.

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      Comment: A review of the option of shorter course antibiotic therapy for right-sided heart infections in injection drug users.

    • Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med. 2013; 41: 580-637. Ref.: https://goo.gl/D8hdSK
    • Macy E, Contreras R.

      Healthcare use of serious infection prevalence associated with penicillin ‘allergy’ in hospitalized patients: a cohort study. J Allergy Clin Immunol. 2014; 133: 790-796. Ref.: https://goo.gl/NyVNQC

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      aureus bacteremia when evaluated with TEE.
      Rating: Important

    • Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis. 2013;56(12):1754-62. [PMID:23457080]

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      This suggests that MRSA is not a common driver of cellulitis in the absence of purulence.

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      7) What is the optimum duration of treatment for SAB? 8) Is oral therapy the equivalent to parenteral? 9) Is combination therapy better than monotherapy? 10) what is the role of linezolid, daptomycin and newer antimicrobials?
      Rating: Important

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      Ref.: https://goo.gl/yNG1GA

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      Comment: For those with severe infections including bacteremia especially, TMP/SMX did not acheive non-inferiority compared to vancomycin. Multivariable logistic regression had trimethoprim-sulfamethoxazole significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).

    • Picard M, Start P, Bouchard H, Cloutier J, Lacombe-Barrios J, et al.

      Treatment of patients with a history of penicillin allergy in a large tertiary-care academic hospital. J Allergy Clin Immunol Pract. 2013; 1: 252-257. Ref.: https://goo.gl/ycXTQp

    • Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010; 50: 133-164. Ref.: https://goo.gl/wSDsPS
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      Comment: Although early valve surgery advocated by numerous, this series did not discover significant benefit.

    • Berbari EF, Kanj SS, Kowalski TJ, et al. Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015;61(6):859-63. [PMID:26316526]

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      Comment: A study of 101 injection drug users with S. aureus infection of whom 65% were bacteremic. The success rate for therapy of MRSA infections was equivalent for the TMP-SMX and vancomycin groups, although vancomycin was marginally more successful as a therapy in the non-MRSA group. The authors thus suggests that TMP-SMX may be a viable alternative to vancomycin for MRSA infection in this group of patients. Failures with TMP/SMX were seen only in the group with endocarditis but not those with straight (or supposedly straight) bacteremia.

      Rating: Important

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      Comment: Best data regarding decolonization efficacy exists in pre-surgical patients and those on dialysis. Efficacy for decreasing CA-MRSA recurrent infections doesn’t yet exist in robust fashion.
      Rating: Important

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      Consequences of avoiding beta-lactams in patients with b-lactam allergies. J Allergy Clin Immunol. 2016; 137: 1148-1153. Ref.: https://goo.gl/G2euqr

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      What is beta lactam allergy

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      Comment: Reasons for limited development of VRSA is unclear (compared to enterococci); however, only 14 isolates described since 2001.

      Final four own been from the state of Delaware.

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      Comment: Recent publication demonstrating that daptomycin is not inferior to standard therapy in the treatment of S. aureus bacteremia and right-sided endocarditis.
      Rating: Important

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      Comment: Fairly large trial in a hard to study condition. RCT examined linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) x 7-14d. Enrolled pts numbered 1184, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042).

      Howvever, all-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). This study suggests that the PK/PD elements favoring linezolid may in fact own clinical efficacy favorable over vancomycin but the larger 60d picture is not telling. For the extremely ill with potential for added complications such as renal failure, linezolid may be the better option.

    • Sharma VK, Sethuraman G, Kumar B. Cutaneous adverse drug reactions: clinical pattern and causative agents- a 6 year series from Chandigarh, India. J Postgrad Med. 2001; 47: 388-393.

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      Comment: As TMP/SMX often thought of as a better staph than strep agent, this study found no diverse between clindamycin or TMP/SMX in those with either abscess, cellulitis or mixed infection.

      This suggests that fretting about choices if more celllulitic vs. abscess scenarios is not necessary for those with mild-moderate infections.

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    • Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

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      Comment: Randomized trial of 509 adults with staphylococcal bacteremia, use of an algorithm compared with usual care resulted in a clinical success rate of 82.0% vs 81.5%, respectively—showing little difference and similar serious adverse events occurred in 32.5% vs 28.3% of patients, a difference that was not statistically significant but with wide confidence intervals. The trial used 14 +/- 2 d for short course vs. 28-42 days for complicated. Trial suggests that staphylococcal bacteremia can be treated by the algorithm if diagnostic and therapeutic recommendations are followed. An exciting sidebar is in the uncomplicated, short-course group, the failure rate was 25-30%.

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      Rating: Important

    • NHS Trade Services Authority, NHS Prescription Services. NHS Electronic Drug Tariff. [Internet]. nhsbsa.nhs.uk
    • Song KH, Jung SI, Lee S, et al. Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics.

      Eur J Clin Microbiol Infect Dis. 2019;38(1):67-74. [PMID:30269181]

      Comment: Among 302 MSSA isolates in this South Korean study representing hospital isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of every tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p <  0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p <  0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively.

      About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p <  0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p <  0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

    • del Río A, Gasch O, Moreno A, et al. Efficacy and safety of fosfomycin plus imipenem as save therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial.

      Clin Infect Dis. 2014;59(8):1105-12. [PMID:25048851]

      Comment: Available in some European and other countries, this little study examined S aureus bacteremia or endocarditis and found that fosfomycin [2g IV q 6] + imipenem appeared to be helpful in those failing regimens including vancomcyin, daptomycin and others. Success rate was 69% of the 16 patients.

    • Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003;290(22):2976-84. [PMID:14665659]

      Comment: A study that elucidates the clinical and microbiologic differences between healthcare-associated MRSA and community-associated MRSA.

      Rating: Important

    • Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996;101(1):68-76. [PMID:8686718]

      Comment: A study comparing standard therapy for right-sided endocarditis to oral ciprofloxacin and rifampin for 4 weeks that demonstrates the efficacy of the oral regimen.

    • Solensky R. Hypersensitivity reactions to beta-lactam antibiotics. Clin Revi Allerg Immu. 2003; 24: 201-220. Ref.: https://goo.gl/CGjKqb
    • Nambiar K, Seifert H, Rieg S, et al. Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of put of care.

      J Infect. 2018;77(6):516-525. [PMID:30179645]

      Comment: Among diverse hospitals, mortality rates among the pooled 1851 patients with a median age of 66 years (64% male) were analyzed. Crude 90-day mortality differed significantly between hospitals (range 23-39%) which authors attributed to numerous factors.

    • Wong BB, Keith PK, Waserman S. Clinical history as a predictor of penicillin skin test outcome.

      Ann Allergy Asthma Immunol. 2006; 97: 169-174. Ref.: https://goo.gl/HRcFRo

    • Cosgrove SE, Carroll KC, Perl TM. Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis. 2004;39(4):539-45. [PMID:15356818]

      Comment: Review of the epidemiology, diagnosis, and management of patients with S.

      What is beta lactam allergy

      aureus with reduced susceptibility to vancomycin.
      Rating: Important

    • Thong BY, Leong KP, Tang CY, Chng HH. Drug Allergy in a general hospital: results of a novel prospective inpatient reporting system. Ann Allergy Asthma Immunol. 2003; 90: 342-347. Ref.: https://goo.gl/nyjuSv
    • Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-32. [PMID:26962903]

      Comment: Rather surprising results from this study that is in contrast to the «no antibiotic needed» dogma for uncomplicated, drained S aureus abscesses.

      Study suggested higher cure rates in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005).

    • Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39: 1267-1284.

      Ref.: https://goo.gl/k85jz5

    • Lee BK, Crossley K, Gerding DN. The association between Staphylococcus aureus bacteremia and bacteriuria. Am J Med. 1978;65(2):303-6. [PMID:686015]

      Comment: The classic paper describing the presence of S. aureus bacteriuria in 27% of patients with S. aureus bacteremia in the absence of obvious renal infection.

    Journal HomeAbout JournalEditorsArchiveSubmit Manuscript

  • Song KH, Jung SI, Lee S, et al. Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics. Eur J Clin Microbiol Infect Dis.

    2019;38(1):67-74. [PMID:30269181]

    Comment: Among 302 MSSA isolates in this South Korean study representing hospital isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of every tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p <  0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p <  0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively.

    About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p <  0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p <  0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

  • Rieg S, von Cube M, Kaasch A, et al. Investigating the impact of early valve surgery on survival in Staphylococcus aureus infective endocarditis using a marginal structural model approach — results of a large prospectively evaluated cohort. Clin Infect Dis. 2018. [PMID:30346527]

    Comment: Although early valve surgery advocated by numerous, this series did not discover significant benefit.

  • Carr DR, Stiefel U, Bonomo RA, et al. A Comparison of Cefazolin Versus Ceftriaxone for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia in a Tertiary Care VA Medical Middle. Open Forum Infect Dis. 2018;5(5):ofy089. [PMID:30568987]
  • Nambiar K, Seifert H, Rieg S, et al. Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of put of care. J Infect. 2018;77(6):516-525. [PMID:30179645]

    Comment: Among diverse hospitals, mortality rates among the pooled 1851 patients with a median age of 66 years (64% male) were analyzed.

    Crude 90-day mortality differed significantly between hospitals (range 23-39%) which authors attributed to numerous factors.

  • Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial. JAMA. 2018;320(12):1249-1258. [PMID:30264119]

    Comment: Randomized trial of 509 adults with staphylococcal bacteremia, use of an algorithm compared with usual care resulted in a clinical success rate of 82.0% vs 81.5%, respectively—showing little difference and similar serious adverse events occurred in 32.5% vs 28.3% of patients, a difference that was not statistically significant but with wide confidence intervals.

    The trial used 14 +/- 2 d for short course vs. 28-42 days for complicated. Trial suggests that staphylococcal bacteremia can be treated by the algorithm if diagnostic and therapeutic recommendations are followed. An exciting sidebar is in the uncomplicated, short-course group, the failure rate was 25-30%.

  • Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555. [PMID:28657870]
  • Talan DA, Mower WR, Krishnadasan A, et al.

    Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-32. [PMID:26962903]

    Comment: Rather surprising results from this study that is in contrast to the «no antibiotic needed» dogma for uncomplicated, drained S aureus abscesses. Study suggested higher cure rates in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005).

  • Berbari EF, Kanj SS, Kowalski TJ, et al. Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015;61(6):859-63. [PMID:26316526]

    Comment: Guidance document suggesting 6 wks of parenteral or highly bioavailable oral therapy for native (no hardware) vertebral osteomyelitis. First line choices for MSSA, recs include nafcillin, oxacillin, cefazolin or ceftriaxone.

    What is beta lactam allergy

    For MRSA, vancomycin or daptomycin.

  • Walters MS, Eggers P, Albrecht V, et al. Vancomycin-Resistant Staphylococcus aureus — Delaware, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(37):1056. [PMID:26402026]

    Comment: Reasons for limited development of VRSA is unclear (compared to enterococci); however, only 14 isolates described since 2001. Final four own been from the state of Delaware.

  • Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections.

    N Engl J Med. 2015;372(12):1093-103. [PMID:25785967]

    Comment: As TMP/SMX often thought of as a better staph than strep agent, this study found no diverse between clindamycin or TMP/SMX in those with either abscess, cellulitis or mixed infection. This suggests that fretting about choices if more celllulitic vs. abscess scenarios is not necessary for those with mild-moderate infections.

  • Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015;350:h2219. [PMID:25977146]

    Comment: For those with severe infections including bacteremia especially, TMP/SMX did not acheive non-inferiority compared to vancomycin.

    Multivariable logistic regression had trimethoprim-sulfamethoxazole significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65). The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).

  • del Río A, Gasch O, Moreno A, et al.

    Efficacy and safety of fosfomycin plus imipenem as save therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial. Clin Infect Dis. 2014;59(8):1105-12. [PMID:25048851]

    Comment: Available in some European and other countries, this little study examined S aureus bacteremia or endocarditis and found that fosfomycin [2g IV q 6] + imipenem appeared to be helpful in those failing regimens including vancomcyin, daptomycin and others.

    Success rate was 69% of the 16 patients.

  • Kaasch AJ, Barlow G, Edgeworth JD, et al. Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J Infect. 2014;68(3):242-51. [PMID:24247070]

    Comment: Five cohorts of S. aureus bacteremia with adjusted HR mortality in this group of 3346 with 30d mortality = 21%, 90d mortality = 29%.

  • Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial.

    Clin Infect Dis. 2013;56(12):1754-62. [PMID:23457080]

    Comment: Interestingly this trial did not propose that adding an agent with activity against CA-MRSA (TMP/SMX) did not substantially improve outcomes [82% cephalexin alone, 85% combination]. This suggests that MRSA is not a common driver of cellulitis in the absence of purulence.

  • Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012;54(5):621-9. [PMID:22247123]

    Comment: Fairly large trial in a hard to study condition. RCT examined linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) x 7-14d.

    Enrolled pts numbered 1184, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). Howvever, all-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). This study suggests that the PK/PD elements favoring linezolid may in fact own clinical efficacy favorable over vancomycin but the larger 60d picture is not telling.

    For the extremely ill with potential for added complications such as renal failure, linezolid may be the better option.

  • Vos FJ, Kullberg BJ, Sturm PD, et al. Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia. Medicine (Baltimore). 2012;91(2):86-94. [PMID:22391470]

    Comment: Study of 115 patients with staph or strep bacteremia using FDG-PET/CT technology looking for metastatic infections found foci in 84 of 115 (73%) patients: endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently.

    Signs or symptoms directing a diagnostic work-up were only present in 41%, suggesting that additional studies may be helpful even in absence of specific findings: for example in this study PET was the first to detect problems in 30%.

  • Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis. 2011;11(3):208-22. [PMID:21371655]

    Comment: Important to note that only 16 studies with < 1500 patients in RCTs form basis for guidance in this hard infection. Authors rightly point out that much guideline recommendations are based on observational or limited case studies.

    Key questions that remain to be answered in their opinion include: 1) How should SAB be defined?, 2) Is identification and removal of infection focus important? 3) Should every SAB pts own echocardiography? 4) Are glycopeptides equivalent to beta-lactams? 5) Are cephalosporins equivalent to penicillins?, 6) Is teicoplanin as effective as vancomycin? 7) What is the optimum duration of treatment for SAB? 8) Is oral therapy the equivalent to parenteral? 9) Is combination therapy better than monotherapy? 10) what is the role of linezolid, daptomycin and newer antimicrobials?
    Rating: Important

  • Dhand A, Bayer AS, Pogliano J, et al.

    Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis. 2011;53(2):158-63. [PMID:21690622]

    Comment: Authors capable to clear persistent bacteremia in 7 pts with combination of daptomycin and oxacillin or nafcillin (2g IV q4h) in seven patients. Mechanism not entirely clear but may be due to enhanced membrane binding of daptomycin in the presence of the beta-lactam.

  • Simor AE. Staphylococcal decolonisation: an effective strategy for prevention of infection?

    Lancet Infect Dis. 2011;11(12):952-62. [PMID:22115070]

    Comment: Best data regarding decolonization efficacy exists in pre-surgical patients and those on dialysis. Efficacy for decreasing CA-MRSA recurrent infections doesn’t yet exist in robust fashion.
    Rating: Important

  • Cosgrove SE, Vigliani GA, Fowler VG, et al. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009;48(6):713-21. [PMID:19207079]

    Comment: Evidence for nephrotoxicity associated with short course synergy dose gentamicin in the treatment of S.

    aureus bacteremia and endocarditis.

  • Figueroa DA, Mangini E, Amodio-Groton M, et al. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program.

    What is beta lactam allergy

    Clin Infect Dis. 2009;49(2):177-80. [PMID:19500039]

    Comment: Single middle study evaluating the safety of higher doses of daptomycin.
    Rating: Important

  • Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-65. [PMID:16914701]

    Comment: Recent publication demonstrating that daptomycin is not inferior to standard therapy in the treatment of S.

    aureus bacteremia and right-sided endocarditis.
    Rating: Important

  • Cosgrove SE, Carroll KC, Perl TM. Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis. 2004;39(4):539-45. [PMID:15356818]

    Comment: Review of the epidemiology, diagnosis, and management of patients with S. aureus with reduced susceptibility to vancomycin.
    Rating: Important

  • Naimi TS, LeDell KH, Como-Sabetti K, et al.

    Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003;290(22):2976-84. [PMID:14665659]

    Comment: A study that elucidates the clinical and microbiologic differences between healthcare-associated MRSA and community-associated MRSA.
    Rating: Important

  • von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia.

    Study Group. N Engl J Med. 2001;344(1):11-6. [PMID:11136954]

    Comment: A German study indicating that S. aureus bacteremia appears to frequently be caused by strains of S. aureus colonizing the patient’s own nasal mucosa. An accompanying editorial emphasizes the importance of attempting to eradicate this colonization in order to control nosocomial infections, but highlights the failure of most currently used agents to achieve this goal (N Engl J Med 2001; 344: 55-57)

  • Fowler VG, Li J, Corey GR, et al.

    Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol. 1997;30(4):1072-8. [PMID:9316542]

    Comment: A study demonstrating the presence of endocarditis in 25% of patients with S. aureus bacteremia when evaluated with TEE.
    Rating: Important

  • Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy.

    Am J Med. 1996;101(1):68-76. [PMID:8686718]

    Comment: A study comparing standard therapy for right-sided endocarditis to oral ciprofloxacin and rifampin for 4 weeks that demonstrates the efficacy of the oral regimen.

  • DiNubile MJ. Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users. Ann Intern Med. 1994;121(11):873-6. [PMID:7978701]

    Comment: A review of the option of shorter course antibiotic therapy for right-sided heart infections in injection drug users.

  • Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med. 1992;117(5):390-8. [PMID:1503330]

    Comment: A study of 101 injection drug users with S. aureus infection of whom 65% were bacteremic. The success rate for therapy of MRSA infections was equivalent for the TMP-SMX and vancomycin groups, although vancomycin was marginally more successful as a therapy in the non-MRSA group. The authors thus suggests that TMP-SMX may be a viable alternative to vancomycin for MRSA infection in this group of patients.

    Failures with TMP/SMX were seen only in the group with endocarditis but not those with straight (or supposedly straight) bacteremia.
    Rating: Important

  • Tranter HS. Foodborne staphylococcal illness. Lancet. 1990;336(8722):1044-6. [PMID:1977028]

    Comment: A review of GI tract infections caused by ingestion of certain toxin-producing strains of S. aureus.

  • Lee BK, Crossley K, Gerding DN. The association between Staphylococcus aureus bacteremia and bacteriuria. Am J Med. 1978;65(2):303-6. [PMID:686015]

    Comment: The classic paper describing the presence of S. aureus bacteriuria in 27% of patients with S.

    aureus bacteremia in the absence of obvious renal infection.

  • Journal HomeAbout JournalEditorsArchiveSubmit Manuscript

  • Song KH, Jung SI, Lee S, et al. Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics. Eur J Clin Microbiol Infect Dis. 2019;38(1):67-74. [PMID:30269181]

    Comment: Among 302 MSSA isolates in this South Korean study representing hospital isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively.

    Mean HI MICs of every tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p <  0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p <  0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p <  0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p <  0.001).

    A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

  • Rieg S, von Cube M, Kaasch A, et al. Investigating the impact of early valve surgery on survival in Staphylococcus aureus infective endocarditis using a marginal structural model approach — results of a large prospectively evaluated cohort. Clin Infect Dis. 2018. [PMID:30346527]

    Comment: Although early valve surgery advocated by numerous, this series did not discover significant benefit.

  • Carr DR, Stiefel U, Bonomo RA, et al. A Comparison of Cefazolin Versus Ceftriaxone for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia in a Tertiary Care VA Medical Middle.

    Open Forum Infect Dis. 2018;5(5):ofy089. [PMID:30568987]

  • Nambiar K, Seifert H, Rieg S, et al. Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of put of care. J Infect. 2018;77(6):516-525. [PMID:30179645]

    Comment: Among diverse hospitals, mortality rates among the pooled 1851 patients with a median age of 66 years (64% male) were analyzed. Crude 90-day mortality differed significantly between hospitals (range 23-39%) which authors attributed to numerous factors.

  • Holland TL, Raad I, Boucher HW, et al.

    Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial. JAMA. 2018;320(12):1249-1258. [PMID:30264119]

    Comment: Randomized trial of 509 adults with staphylococcal bacteremia, use of an algorithm compared with usual care resulted in a clinical success rate of 82.0% vs 81.5%, respectively—showing little difference and similar serious adverse events occurred in 32.5% vs 28.3% of patients, a difference that was not statistically significant but with wide confidence intervals.

    The trial used 14 +/- 2 d for short course vs. 28-42 days for complicated. Trial suggests that staphylococcal bacteremia can be treated by the algorithm if diagnostic and therapeutic recommendations are followed. An exciting sidebar is in the uncomplicated, short-course group, the failure rate was 25-30%.

  • Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555. [PMID:28657870]
  • Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med.

    2016;374(9):823-32. [PMID:26962903]

    Comment: Rather surprising results from this study that is in contrast to the «no antibiotic needed» dogma for uncomplicated, drained S aureus abscesses. Study suggested higher cure rates in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005).

  • Berbari EF, Kanj SS, Kowalski TJ, et al. Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015;61(6):859-63. [PMID:26316526]

    Comment: Guidance document suggesting 6 wks of parenteral or highly bioavailable oral therapy for native (no hardware) vertebral osteomyelitis. First line choices for MSSA, recs include nafcillin, oxacillin, cefazolin or ceftriaxone. For MRSA, vancomycin or daptomycin.

  • Walters MS, Eggers P, Albrecht V, et al.

    Vancomycin-Resistant Staphylococcus aureus — Delaware, 2015.

    What is beta lactam allergy

    MMWR Morb Mortal Wkly Rep. 2015;64(37):1056. [PMID:26402026]

    Comment: Reasons for limited development of VRSA is unclear (compared to enterococci); however, only 14 isolates described since 2001. Final four own been from the state of Delaware.

  • Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372(12):1093-103. [PMID:25785967]

    Comment: As TMP/SMX often thought of as a better staph than strep agent, this study found no diverse between clindamycin or TMP/SMX in those with either abscess, cellulitis or mixed infection. This suggests that fretting about choices if more celllulitic vs.

    abscess scenarios is not necessary for those with mild-moderate infections.

  • Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015;350:h2219. [PMID:25977146]

    Comment: For those with severe infections including bacteremia especially, TMP/SMX did not acheive non-inferiority compared to vancomycin. Multivariable logistic regression had trimethoprim-sulfamethoxazole significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65).

    The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).

  • del Río A, Gasch O, Moreno A, et al. Efficacy and safety of fosfomycin plus imipenem as save therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial. Clin Infect Dis. 2014;59(8):1105-12. [PMID:25048851]

    Comment: Available in some European and other countries, this little study examined S aureus bacteremia or endocarditis and found that fosfomycin [2g IV q 6] + imipenem appeared to be helpful in those failing regimens including vancomcyin, daptomycin and others.

    Success rate was 69% of the 16 patients.

  • Kaasch AJ, Barlow G, Edgeworth JD, et al. Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J Infect. 2014;68(3):242-51. [PMID:24247070]

    Comment: Five cohorts of S. aureus bacteremia with adjusted HR mortality in this group of 3346 with 30d mortality = 21%, 90d mortality = 29%.

  • Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis. 2013;56(12):1754-62. [PMID:23457080]

    Comment: Interestingly this trial did not propose that adding an agent with activity against CA-MRSA (TMP/SMX) did not substantially improve outcomes [82% cephalexin alone, 85% combination]. This suggests that MRSA is not a common driver of cellulitis in the absence of purulence.

  • Wunderink RG, Niederman MS, Kollef MH, et al.

    Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012;54(5):621-9. [PMID:22247123]

    Comment: Fairly large trial in a hard to study condition. RCT examined linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) x 7-14d. Enrolled pts numbered 1184, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042).

    Howvever, all-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). This study suggests that the PK/PD elements favoring linezolid may in fact own clinical efficacy favorable over vancomycin but the larger 60d picture is not telling. For the extremely ill with potential for added complications such as renal failure, linezolid may be the better option.

  • Vos FJ, Kullberg BJ, Sturm PD, et al. Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia.

    Medicine (Baltimore). 2012;91(2):86-94. [PMID:22391470]

    Comment: Study of 115 patients with staph or strep bacteremia using FDG-PET/CT technology looking for metastatic infections found foci in 84 of 115 (73%) patients: endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently. Signs or symptoms directing a diagnostic work-up were only present in 41%, suggesting that additional studies may be helpful even in absence of specific findings: for example in this study PET was the first to detect problems in 30%.

  • Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, et al.

    Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis. 2011;11(3):208-22. [PMID:21371655]

    Comment: Important to note that only 16 studies with < 1500 patients in RCTs form basis for guidance in this hard infection. Authors rightly point out that much guideline recommendations are based on observational or limited case studies. Key questions that remain to be answered in their opinion include: 1) How should SAB be defined?, 2) Is identification and removal of infection focus important? 3) Should every SAB pts own echocardiography? 4) Are glycopeptides equivalent to beta-lactams?

    5) Are cephalosporins equivalent to penicillins?, 6) Is teicoplanin as effective as vancomycin? 7) What is the optimum duration of treatment for SAB? 8) Is oral therapy the equivalent to parenteral? 9) Is combination therapy better than monotherapy? 10) what is the role of linezolid, daptomycin and newer antimicrobials?
    Rating: Important

  • Dhand A, Bayer AS, Pogliano J, et al. Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis. 2011;53(2):158-63. [PMID:21690622]

    Comment: Authors capable to clear persistent bacteremia in 7 pts with combination of daptomycin and oxacillin or nafcillin (2g IV q4h) in seven patients.

    Mechanism not entirely clear but may be due to enhanced membrane binding of daptomycin in the presence of the beta-lactam.

  • Simor AE. Staphylococcal decolonisation: an effective strategy for prevention of infection? Lancet Infect Dis. 2011;11(12):952-62. [PMID:22115070]

    Comment: Best data regarding decolonization efficacy exists in pre-surgical patients and those on dialysis. Efficacy for decreasing CA-MRSA recurrent infections doesn’t yet exist in robust fashion.
    Rating: Important

  • Cosgrove SE, Vigliani GA, Fowler VG, et al.

    Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009;48(6):713-21. [PMID:19207079]

    Comment: Evidence for nephrotoxicity associated with short course synergy dose gentamicin in the treatment of S. aureus bacteremia and endocarditis.

  • Figueroa DA, Mangini E, Amodio-Groton M, et al. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis.

    2009;49(2):177-80. [PMID:19500039]

    Comment: Single middle study evaluating the safety of higher doses of daptomycin.
    Rating: Important

  • Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-65. [PMID:16914701]

    Comment: Recent publication demonstrating that daptomycin is not inferior to standard therapy in the treatment of S.

    aureus bacteremia and right-sided endocarditis.
    Rating: Important

  • Cosgrove SE, Carroll KC, Perl TM. Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis. 2004;39(4):539-45. [PMID:15356818]

    Comment: Review of the epidemiology, diagnosis, and management of patients with S. aureus with reduced susceptibility to vancomycin.
    Rating: Important

  • Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.

    JAMA. 2003;290(22):2976-84. [PMID:14665659]

    Comment: A study that elucidates the clinical and microbiologic differences between healthcare-associated MRSA and community-associated MRSA.
    Rating: Important

  • von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001;344(1):11-6. [PMID:11136954]

    Comment: A German study indicating that S. aureus bacteremia appears to frequently be caused by strains of S. aureus colonizing the patient’s own nasal mucosa.

    An accompanying editorial emphasizes the importance of attempting to eradicate this colonization in order to control nosocomial infections, but highlights the failure of most currently used agents to achieve this goal (N Engl J Med 2001; 344: 55-57)

  • Fowler VG, Li J, Corey GR, et al. Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol. 1997;30(4):1072-8. [PMID:9316542]

    Comment: A study demonstrating the presence of endocarditis in 25% of patients with S. aureus bacteremia when evaluated with TEE.

    Rating: Important

  • Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996;101(1):68-76. [PMID:8686718]

    Comment: A study comparing standard therapy for right-sided endocarditis to oral ciprofloxacin and rifampin for 4 weeks that demonstrates the efficacy of the oral regimen.

  • DiNubile MJ. Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users. Ann Intern Med. 1994;121(11):873-6.

    [PMID:7978701]

    Comment: A review of the option of shorter course antibiotic therapy for right-sided heart infections in injection drug users.

  • Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med. 1992;117(5):390-8. [PMID:1503330]

    Comment: A study of 101 injection drug users with S. aureus infection of whom 65% were bacteremic. The success rate for therapy of MRSA infections was equivalent for the TMP-SMX and vancomycin groups, although vancomycin was marginally more successful as a therapy in the non-MRSA group.

    The authors thus suggests that TMP-SMX may be a viable alternative to vancomycin for MRSA infection in this group of patients. Failures with TMP/SMX were seen only in the group with endocarditis but not those with straight (or supposedly straight) bacteremia.
    Rating: Important

  • Tranter HS. Foodborne staphylococcal illness. Lancet. 1990;336(8722):1044-6. [PMID:1977028]

    Comment: A review of GI tract infections caused by ingestion of certain toxin-producing strains of S. aureus.

  • Lee BK, Crossley K, Gerding DN. The association between Staphylococcus aureus bacteremia and bacteriuria.

    Am J Med. 1978;65(2):303-6. [PMID:686015]

    Comment: The classic paper describing the presence of S. aureus bacteriuria in 27% of patients with S. aureus bacteremia in the absence of obvious renal infection.


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