Treatment of sepsis: What is the antibiotic choice in bacteremia due to carbapenem resistantEnterobacteriaceae?

Abstract

Sepsis is one of the major challenges of today. Although gram-positive bacteria related infections are more prevalent in hospital setting, the highest mortality rate is associated with gram-negative microorganisms especially Enterobacteriaceae. Enterobacteriaceae, including Escherichia coli, Klebsiella spp., Proteus spp., Enterobacter spp. and Serratia spp. Resistance to β-lactams in Enterobacteriaceae is primarily attributed to the production of B-lactamase enzymes with subsequent antibiotic hydrolysis and to a lesser extent by alteration of efflux pump or porins expression. Carbapenem resistant Enterobacteriaceae (CRE) and Acinetobacter baumannii are the most notorious pathogens due to the high incidence of morbidity and mortality especially in the immunocompromised patients in the intensive care unit. The most appropriate antimicrobial therapy to treat CRE is still controversial. Combination therapy is preferred over monotherapy due to its broad-spectrum coverage of micro-organisms, due to its synergetic effect and to prevent development of further resistance. Current suggested therapies for CRE resistance as well as promising antibiotics that are currently under investigation for winning the war against the emerging CRE resistance are reviewed and discussed.

Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia

“…In addition to reducing the development of resistance in the clinic and the environment (30), accumulating evidence shows that combination therapy boosts survival compared to monotherapy, especially in patients with bacteremia and patients who are critically ill (31)(32)(33). Similarly, we found that combination therapy seems to be more effective than monotherapy, although monotherapy is not any more effective than therapy with inactive drugs, as previously reported by Tzouvelekis et al (34).…”

“…mortality in the tigecycline monotherapy group. Although an optimal combination therapy against CRE has not yet been established (30), combination therapy that includes meropenem was associated with significantly better survival. Indeed, regimens based on two carbapenems were previously recommended for CRKP infection when meropenem MICs were Յ8 mg/liter (11,33).…”

Rapid profiling of the preterm infant gut microbiota using nanopore sequencing aids pathogen diagnostics

“…However, genes including imiS 54 , NDM-9 55 , or THIN-B 56 (which may encode carbapenemase activity against meropenem) indicates meropenem treatment alone may not be sufficient to clear this K. pneumoniae infection, and a combination therapy e.g. meropenem with ertapenem may be required 57 . Overall, information at only 10 hours, which would correlate with presentation of first NEC symptoms, is clinically very relevant and potentially provides important information on the pathogen involved and associated AMR profiles that may guide antibiotic treatment choices.…”

Current Diagnosis and Treatment Approach to Sepsis

“…However, there are also studies showing that early combination therapy is associated with lower mortality in patients with septic shock [83] . Combination therapy is preferred when treating sepsis patients for whom carbapenem-resistant Enterobacteriaceae (CRE) is considered the causative agent, due to its synergistic effect and to prevent the development of resistance [84] . Combination therapy with aminoglycoside has been associated with higher survival rates in cases of sepsis and septic shock due to Gram-negative bacteria with high risk of MDR, such as Pseudomonas spp.…”