Clinical Studies
Differential effect of prior β-lactams and fluoroquinolones on risk of bloodstream infections secondary to Pseudomonas aeruginosa

https://doi.org/10.1016/j.diagmicrobio.2016.09.017Get rights and content

Abstract

Objective

This retrospective case–control study examines risk factors for bloodstream infections (BSI) due to Pseudomonas aeruginosa (PSA).

Methods

Hospitalized adults with Gram-negative BSI at Palmetto Health from 2010 to 2015 were identified. Multivariate logistic regression was used to examine PSA BSI risk factors.

Results

Seventy and 910 patients with PSA and Enterobacteriaceae BSI, respectively, were included. Prior use of β-lactams (adjusted odds ratio [aOR] 3.9, 95% confidence intervals [CI]: 2.3–6.9), but not fluoroquinolones (aOR 1.0, 95% CI: 0.4–2.2), was a risk factor for PSA BSI. Immune compromised status (aOR 3.7, 95% CI: 2.0–6.7), respiratory source (aOR 4.4, 95% CI: 2.1–8.9), and prolonged hospitalization (aOR 1.9, 95% CI: 1.1–3.5), were predictors of PSA BSI.

Conclusions

Determination of class of previously used antibiotics among other clinical variables helps identify patients at risk of PSA BSI and offers opportunities to optimize empirical antimicrobial therapy.

Introduction

Appropriate empirical antimicrobial therapy has been associated with improved survival in patients with bloodstream infections (BSI) (Cain et al., 2015, Paul et al., 2010, Retamar et al., 2012). However, the non-stratified use of broad-spectrum antimicrobial agents is not without major adverse events. Identification of patients at risk of BSI due to Gram-negative bacilli that express antimicrobial resistance genes is essential to increase the benefit-to-risk ratio of antimicrobial therapy.

Pseudomonas aeruginosa is intrinsically resistant to various antimicrobial agents because of the presence of chromosomally-mediated AmpC β-lactamase, a low permeability of its outer membrane and the constitutive expression of efflux pumps (Lambert, 2002). P. aeruginosa is among the top five most commonly isolated Gram-negative bacilli in blood cultures in population-based and other large surveillance studies (Al-Hasan et al., 2008, Decousser et al., 2003, Diekema et al., 1999, Parkins et al., 2010). There have been reports of a temporal increase in the incidence rate of BSI due to P. aeruginosa over the past decade in the USA (Werth et al., 2015). The case fatality rates following BSI due to P. aeruginosa have ranged from 15% to 30% in recent studies (Al-Hasan et al., 2008, Cheong et al., 2008, Parkins et al., 2010).

Identification of patients at risk of BSI due to P. aeruginosa may help optimize empirical antimicrobial therapy and improve utilization of broad-spectrum antimicrobial agents. Prior use of antimicrobial agents has been associated with increased risk of infections due to multi-drug resistant P. aeruginosa (Aloush et al., 2006, Gransden et al., 1995, Schechner et al., 2009). However, the differential impact of prior β-lactam and fluoroquinolone exposure on the risk of BSI due to P. aeruginosa is not clearly defined. This retrospective case–control study examines the impact of prior exposure to β-lactams and fluoroquinolones among other risk factors for P. aeruginosa BSI.

Section snippets

Setting

The study is conducted at Palmetto Health Richland and Baptist Hospitals in Columbia, SC, USA, which combined have over 1100 licensed beds. The hospitals provide medical, surgical and subspecialty care for residents of Richland County and surrounding areas in South Carolina. Palmetto Health is affiliated with multiple acute care hospitals, emergency rooms and urgent treatment centers as well as numerous ambulatory clinics in the region. The Institutional Review Board at Palmetto Health approved

Results

During the study period, 70 patients with BSI due to P. aeruginosa (cases) and 910 due to Enterobacteriaceae (controls) were included. Escherichia coli (597; 66%) was the most common bloodstream isolate among Enterobacteriaceae, followed by Klebsiella pneumoniae (211; 23%), Proteus mirabilis (78; 9%), Klebsiella oxytoca (14; 2%) and Salmonella species (10; 1%).

Overall, the median age was 66 years and 444 (45%) were men. The study population was ethnically diverse: 461 (47%) Caucasians, 486 (50%)

Discussion

The current study demonstrates a differential effect of prior β-lactam and fluoroquinolone exposure on the risk of BSI secondary to P. aeruginosa. Prior use of β-lactams, but not fluoroquinolones, is identified as an independent risk factor for P. aeruginosa BSI. The association between exposure to antimicrobial agents and P. aeruginosa BSI is consistent with the results of previous studies (Gransden et al., 1995, Schechner et al., 2009). However, stratification of prior use of antimicrobial

Funding

The study had no funding source.

Transparency declarations and potential conflicts of interest

KLH, JAJ, JK, HA and MNA: no conflicts.

PBB: Research advisory board for Actavis Pharmaceuticals (now Allergan); research funding from Actavis Pharmaceuticals (now Allergan).

Acknowledgments

The authors thank the Antimicrobial Stewardship and Support Team at Palmetto Health in Columbia, South Carolina, USA for their help in facilitating the conduction of this study.

The preliminary results of this study were presented, in part, at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy on September 7, 2014 in Washington, DC, USA (Abstract K-1050).

KLH and MNA have full access to all of the data in the study and take responsibility for the integrity of the data and

References (28)

  • R. Banerjee et al.

    Escherichia coli Sequence type 131 is a dominant, antimicrobial-resistant clonal group associated with healthcare and elderly hosts

    Infect Control Hosp Epidemiol

    (2013)
  • S.E. Cain et al.

    Stratification of the impact of inappropriate empirical antimicrobial therapy for gram-negative bloodstream infections by predicted prognosis

    Antimicrob Agents Chemother

    (2015)
  • N. Cobos-Trigueros et al.

    Acquisition of Pseudomonas aeruginosa and its resistance phenotypes in critically ill medical patients: role of colonization pressure and antibiotic exposure

    Crit Care

    (2015)
  • J.W. Decousser et al.

    Frequency of isolation and antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections: a French prospective national survey

    J Antimicrob Chemother

    (2003)

    • Cited by (21)

    • Prediction of mortality in Staphylococcus aureus bloodstream infection using quick Pitt bacteremia score

      2022, Journal of Infection
      Citation Excerpt :

      Otherwise, it was considered community-onset SAB. Immune compromised hosts were defined as those with neutropenia (absolute neutrophil count <500/μL), recent chemotherapy within 30 days of BSI, Acquired Immune Deficiency Syndrome (AIDS), transplant recipients, treatment with corticosteroids (equivalent of prednisone 20 mg daily or higher for at least 1 week) or other immune suppressive medications 10. Indwelling prosthetic devices included cardiac and orthopedic hardware such as artificial heart valves, automatic implantable cardioverter-defibrillator or pacemaker, artificial joints, and other implanted metal material.

    • Evaluation of early clinical failure criteria for gram-negative bloodstream infections

      2020, Clinical Microbiology and Infection
      Citation Excerpt :

      GN-BSI was defined as monomicrobial growth of any aerobic or facultative anaerobic Gram-negative bacillus in a blood culture. Primary source of BSI, site of infection acquisition and immunocompromised status were previously defined [15–17]. Appropriateness of empirical antimicrobial therapy was based on dose, route and in vitro antimicrobial susceptibility testing results [3].

    • Syndrome-specific versus prospective audit and feedback interventions for reducing use of broad-spectrum antimicrobial agents

      2019, American Journal of Infection Control
      Citation Excerpt :

      AST recommended discontinuation of piperacillin/tazobactam in patients without evidence of bacterial infections and a stop date, whenever possible, if treatment was considered appropriate. De-escalation of therapy to agents without P aeruginosa coverage was recommended in patients without positive cultures or clinical risk factors for P aeruginosa.9,13 Alternative antipseudomonal agents were suggested in patients who had microbiological documentation or clinical risk factors for P aeruginosa infections, but for whom risk of nephrotoxicity from continuation of piperacillin/tazobactam was considered high due to concomitant vancomycin use.

    • Acute kidney injury should not be neglected – optimization of quick Pitt bacteremia score for predicting mortality in critically ill patients with bloodstream infection: a retrospective cohort study

      2024, Therapeutic Advances in Infectious Disease

    • Novel evidence on sepsis-inducing pathogens: from laboratory to bedside

      2023, Frontiers in Microbiology

    • Association between duration of antipseudomonal beta-lactam therapy and Clostridioides difficile infections in monomicrobial Enterobacterales bloodstream infections at an academic medical center

      2022, Antimicrobial Stewardship and Healthcare Epidemiology
    View all citing articles on Scopus
    View full text
    © 2016 Elsevier Inc. All rights reserved.