β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

Abstract

The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy The efficacy of combination antimicrobial therapy in patients with bacteremia caused by gram-negative bacilli has been previously examined. The majority of studies have included beta-lactam and aminoglycoside antibiotic combinations. Overall, there was no significant reduction in mortality with beta-lactam and aminoglycoside combinations compared to beta-lactam monotherapy in patients with bacteremia caused by gram-negative bacilli (16,18,25). However, decreased mortality was demonstrated in subgroups of patients with Pseudomonas aeruginosa bacteremia (4, 14, 25) and critically ill patients with Klebsiella species bacteremia (17). A clinical benefit with combination therapy was also seen in neutropenic patients with bacteremia caused by gram-negative bacilli (10, 18). As a result, beta-lactam and aminoglycoside combination therapy has been frequently used in patients with P. aeruginosa bacteremia, but not in patients with bacteremia due to other gram-negative bacilli (6). This approach is particularly useful in patients with risk factors for P. aeruginosa bacteremia for whom combination therapy is started empirically; otherwise, there is little benefit if the decision to start combination therapy is delayed until a gram-negative organism in blood cultures is identified (4,14,15). In addition, due to the potential drug-related adverse events associated with aminoglycosides in critically ill patients, particularly nephrotoxicity, empirical use of these drugs has been limited (21,26).With the increase in antibiotic resistance among gram-negative bacilli, use of combination antibiotic therapy for bacteremia caused by gram-negative bacilli has reemerged. Studies have shown that inappropriate antimicrobial treatment can be reduced with empirical administration of combination therapy (19). Despite the increasing use of fluoroquinolones due to their r...

Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus

“…c Typically require dual broad-spectrum antibiotics with overlapping coverage [189][190][191][192]. d In patients with a history of IV drug use, those with indwelling vascular catheters or devices, or those with recent hospitalizations an agent such as daptomycin (in absence of pneumonia) or vancomycin (IF mic ≤1) or linezolid (in absence of bacteremia) should be adopted.…”

Epidemiology and Outcome of Klebsiella Species Bloodstream Infection: A Population-Based Study

“…[1][2][3][4][5] Population-based studies that specifically address the epidemiology and outcome of Klebsiella spp BSI are lacking because most previous studies have been derived from referral tertiary care centers. [6][7][8] Therefore, we performed a population-based study to determine the incidence rate of Klebsiella spp BSI and to investigate for temporal changes and seasonal variation in the incidence rate of Klebsiella spp BSI.…”

Bacterial sepsis

“…A general combination therapy comprising two (or more) broad-spectrum antibiotics cannot be recommended due to the inconsistency of current data. Some studies have demonstrated reduced mortality achieved by combination therapy [127][128][129][130][131][132], whereas the randomized multicentric comparison of two antibiotic regimens (meropenem vs. meropenem + moxifloxacin) in the treatment of severe sepsis and septic shock by Brunkhorst et al (Max-Sep study; [133]) found no superiority of combination treatment (meropenem + moxifloxacin) over monotherapy (meropenem) for severe sepsis. In this study, mortality 28 days after randomization was 23.9% (95%CI 19-29.4%) in the combination group and 21.9% (95%CI 17.1-27.4%) in the monotherapy group.…”

“…To summarize, it must be stated that primary combination therapy of sepsis was never superior when the antibiotic used as monotherapy was a carbapenem. Moreover, in retrospective analyses it could be shown that in only about 30% of patients did the initial calculated antibiotic therapy actually encompass the pathogen, and de-escalation of therapy was only undertaken in a third of patients [127][128][129][130][131][132][133]. Combining broad-spectrum antibiotics simultaneously potentiates the selective pressure on pathogens and leads to increased development of resistance [134].…”