Archive for February 19, 2017

Editorial Commentary – Combination Therapy for Pseudomonas aeruginosa Bacteremia: Where Do We Stand?

Clinical Infectious Diseases July 15, 2013 V.57 N.2 P.217-220

Mical Paul and Leonard Leibovici

Correspondence: Mical Paul, MD, Unit of Infectious Diseases, Rambam Healthcare Campus, 6 Ha’Aliya Street, Haifa 31096, Israel (

Substantial evidence from randomized controlled trials (RCTs) refutes an advantage to β-lactam–aminoglycoside combination therapy for sepsis [1]. However, there are gaps in this body of evidence. The number of patients with gram-negative bacteremia evaluated for mortality in all trials to date amounts to fewer than 200 [1]; patients with Pseudomonas aeruginosa bacteremia have not been evaluated separately; and patients with septic shock are usually excluded from RCTs [2]. In general, patients included in RCTs are not representative of the patient population seen in general practice [3]. In this issue of Clinical Infectious Diseases, Peña et al present the first large prospective study of P. aeruginosa bacteremia, specifically addressing the issue of combination therapy versus monotherapy [4]. Special reasons exist for the focus on P. aeruginosa, including the paucity of treatment options, in vitro data suggesting synergy [5], and the high mortality associated with P. aeruginosa bacteremia [6]. Indeed, in Peña’s contemporary cohort, the 30-day mortality following P. aeruginosa bacteremia was 30%.


The 2 main reasons quoted in favor of combination therapy for P. aeruginosa bacteremia are to increase the probability of appropriate empirical coverage and to improve overall the antibiotics’ activity through synergism. Peña et al’s study addresses the question of synergy. The authors examined the association of combination therapy with survival among patients when all antibiotics were covering. Both in the empirical and definitive stages of treatment, no significant advantage to combination therapy was observed in this largest cohort to date including 632 episodes of P. aeruginosa …



February 19, 2017 at 11:42 am

Effect of Adequate Single-Drug vs Combination Antimicrobial Therapy on Mortality in Pseudomonas aeruginosa Bloodstream Infections: A Post Hoc Analysis of a Prospective Cohort

Clinical Infectious Diseases July 15, 2013 V.57 N.2 P.208-216

Carmen Peña, Cristina Suarez, Alain Ocampo-Sosa, Javier Murillas, Benito Almirante, Virginia Pomar, Manuela Aguilar, Ana Granados, Esther Calbo, Jesús Rodríguez-Baño, Fernando Rodríguez, Fe Tubau, Antonio Oliver, Luis Martínez-Martínez, and for the Spanish Network for Research in Infectious Diseases (REIPI)

1Servicio de Enfermedades Infecciosas, Hospital Universitario de Bellvitge–IDIBELL, Barcelona

2Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla–IFIMAV, Santander

3Servicio de Microbiología y Unidad de Enfermedades Infecciosas, Hospital Universitario de Son Espases, Palma de Mallorca

4Servicio de Enfermedades Infecciosas, Hospital Universitario Vall d’Hebrón

5Unidad de Enfermedades Infecciosas, Hospital Santa Creu i Sant Pau, Barcelona

6Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocío, Sevilla

7Sección de Enfermedades Infecciosas, Consorci Hospitalari Parc Taulí, Sabadell

8Sección de Enfermedades Infecciosas, Hospital Mutua de Terrasa

9Sección de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla

10Servicio de Microbiología Infecciosas, Hospital Universitario Reina Sofía–IMIBIC, Córdoba

11Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain


Empirical combination therapy is recommended for patients with known or suspected Pseudomonas aeruginosa (PA) infection as a means to decrease the likelihood of administering inadequate antimicrobial treatment, to prevent the emergence of resistance, and to achieve a possible additive or even synergistic effect.


We performed a post hoc analysis of patients with PA bloodstream infections from a published prospective cohort. Mortality was compared in patients treated with adequate empirical and definitive combination therapy (AECT, ADCT), and adequate empirical and definitive single-drug therapy (AESD, ADSD). Confounding was controlled by Cox regression analysis, and a propensity score for receiving AECT or ADCT was also used.


The final cohort comprised 593 patients with a single episode of PA bacteremia. The 30-day mortality was 30% (176 patients); 76 patients (13%) died during the first 48 hours. The unadjusted probabilities of survival until day 30 were 69.4% (95% confidence interval [CI], 59.1–81.6) for the patients receiving AECT, 73.5% (95% CI, 68.4%–79.0%) for the AESD group, and 66.7% (95% CI, 61.2%–72.7%) for patients who received inadequate empirical therapy (P = .17, log-rank test). After adjustment for confounders, the AESD group (adjusted hazard ratio [AHR], 1.17; 95% CI, .70–1.96; P = .54) and patients who received ADSD (AHR, 1.34; 95% CI, .73–2.47; P = .35) showed no association with 30-day mortality compared with the AECT and ADCT groups, respectively.


These results suggests that treatment with combination antimicrobial therapy did not reduce the mortality risk compared with single-drug therapy in PA bloodstream infections. Empirical combination therapy is recommended for patients with known or suspected Pseudomonas aeruginosa (PA). A post hoc analysis of patients with PA bloodstream infections suggests that treatment with combination antimicrobial therapy did not reduce the mortality risk compared with single-drug therapy.


February 19, 2017 at 11:40 am

Discontinuation of Contact Precautions for Methicillin-Resistant Staphylococcus aureus: A Randomized Controlled Trial Comparing Passive and Active Screening With Culture and Polymerase Chain Reaction

Clinical Infectious Diseases July 15, 2013 V.57 N.2 P.176-184

Erica S. Shenoy, JiYeon Kim, Eric S. Rosenberg, Jessica A. Cotter, Hang Lee, Rochelle P. Walensky, and David C. Hooper

1Harvard Medical School

2Division of Infectious Diseases, Department of Medicine

3Biostatistics Center

4Center for AIDS Research

5Department of Pathology

6Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts


There have been no randomized controlled trials comparing active and passive screening for documenting clearance of colonization with methicillin-resistant Staphylococcus aureus (MRSA). We compared the efficacy of active and passive screening using both culture and commercial polymerase chain reaction (PCR) for documentation of MRSA clearance and discontinuation of MRSA contact precautions (CPs).


Inpatients with a history of MRSA infection or colonization enrolled between December 2010 and September 2011 were randomized to either passive (nonintervention arm; n = 202; observation with local standard of care) or active screening (intervention arm; n = 405; study staff screened using culture and commercial PCR). The primary outcome was discontinuation of CPs by trial arm based on 3 negative cultures. In the intervention arm, sensitivity, specificity, and positive and negative predictive values of the first PCR were compared to cultures.


CPs were discontinued significantly more often (rate ratio [RR], 4.1; 95% confidence interval [CI], 2.3%–7.1%) in the intervention arm, including in an intent-to-screen analysis (RR, 2.6; 95% CI, 1.5%–4.7%). The first PCR, compared to 3 cultures, detected MRSA with a sensitivity of 93.9% (95% CI, 85.4%–97.6%), a specificity of 92.0% (95% CI, 85.9%–95.6%), a positive predictive value of 86.1% (95% CI, 75.9%–93.1%), and a negative predictive value of 96.6% (95% CI, 91.6%–99.1%).


Compared to passive screening using culture methods, active screening resulted in discontinuation of MRSA CPs at a significantly higher frequency. Active screening with a single PCR would significantly increase the completion of the screening process. In this randomized controlled trial, active screening was superior to passive screening for discontinuation of contact precautions for methicillin-resistant Staphylococcus aureus, and a single negative nasal swab processed by polymerase chain reaction had a high negative predictive value compared to 3 nasal cultures. Clinical Trials Registration. NCT01234831.


February 19, 2017 at 11:35 am


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