The Ecology of Antibiotic Use in the ICU: Homogeneous Prescribing of Cefepime but Not Tazocin Selects for Antibiotic Resistant Infection

Abstract

Background Antibiotic homogeneity is thought to drive resistance but in vivo data are lacking. In this study, we determined the impact of antibiotic homogeneity per se, and of cefepime versus antipseudomonal penicillin/β-lactamase inhibitor combinations (APP-β), on the likelihood of infection or colonisation with antibiotic resistant bacteria and/or two commonly resistant nosocomial pathogens (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ). A secondary question was whether antibiotic cycling was associated with adverse outcomes including mortality, length of stay, and antibiotic resistance. Methods We evaluated clinical and microbiological outcomes in two similar metropolitan ICUs, which both alternated cefepime with APP-β in four-month cycles. All microbiological isolates and commensal samples were analysed for the presence of antibiotic-resistant bacteria including MRSA and P. aeruginosa . Results Length of stay, mortality and overall antibiotic resistance were unchanged after sixteen months. However, increased colonisation and infection by antibiotic-resistant bacteria were observed in cefepime cycles, returning to baseline in APP-β cycles. Cefepime was the strongest risk factor for acquisition of antibiotic-resistant infection. Conclusions Ecological effects of different β-lactam antibiotics may be more important than specific activity against the causative agents or the effect of antibiotic homogeneity in selection for antibiotic resistance. This has important implications for antibiotic policy.

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

“…However, data relating to the ecological impact on the microbiota suggest that third generation cephalosporins and cefepime are more likely to result in subsequent infection with P aeruginosa, ESBL producing Enterobacteriaceae, and multiply resistant S aureus and Clostridium difficile. [184][185][186] It is currently unclear exactly what "appropriate" antibiotic prescribing is, and translational research is urgently needed in this area. 187 Indeed, it has been argued that an aggressive antibiotic based curative policy promotes the resistance it aims to avoid.…”

“…255 Certain antibiotics such as third generation cephalosporins have long been known to be associated with colonization and infection by opportunistic and antibiotic resistant pathogens including C difficile. 186 Differential colonization effects are evident within 48 hours of admission to intensive care, 185 and these antibiotics may be associated with less effective spontaneous recovery of phylum level balance within gut microflora compared with those without such associations. 184 A better understanding of the effect of probiotics and antibiotics on the gut microflora is therefore essential.…”

Recommendations for the control of carbapenemase-producing Enterobacteriaceae (CPE): A guide for acute care health facilities

“…Local prophylaxis, empirical and treatment guidelines need to consider strategies that reduce the use of antimicrobial classes that are more likely to drive emergence and spread of multidrug-resistant pathogens. In the case of multidrug-resistant gram-negative bacteria such as CPE, reports strongly implicate fluoroquinolones, extended-spectrum cephalosporins and carbapenems [39,40]. Reduction in hospital or community antimicrobial use may be followed by decreased bacterial resistance rates, even where patients or communities have high levels of colonisation with multidrug-resistant bacteria [40].…”

Fitness Landscapes Reveal Simple Strategies for Steering Evolution to Minimize Antibiotic Resistance

“…Strategies that minimize resistance in the long run may be impractical if they involve short-term costs: hospitals cannot sacrifice patients in May to improve outcomes in December (e.g., [38]). A more defensible approach is to select the antibiotic that minimizes the expected growth rate given the current population.…”