Efficacy of polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis

Abstract

In recent years, carbapenem-resistant Enterobacteriaceae has become endemic in many countries. Because of limited treatment options, the abandoned "old antibiotics", polymyxins, have been reintroduced to the clinic. To evaluate the clinical efficacy of polymyxins in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae, we systemically searched the PubMed, Embase, and Cochrane Library databases and analyzed the available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement were followed, and the I(2) method was used for heterogeneity. Nineteen controlled and six single-arm cohort studies comprising 1086 patients met the inclusion criteria. For controlled studies, no significant difference was noted for overall mortality (OR, 0.79; 95% CI, 0.58-1.08; p=0.15), clinical response rate (OR, 1.24; 95% CI, 0.61-2.54; p=0.55), or microbiological response rate (OR, 0.59; 95% CI, 0.26-1.36; p=0.22) between polymyxin-treated groups and the control groups. Subgroup analyses showed that 28-day or 30-day mortality was lower in patients who received polymyxin combination therapy than in those who received monotherapy (OR, 0.36; 95% CI, 0.19-0.68; p<0.01) and the control groups (OR, 0.49; 95% CI, 0.31-0.75; p<0.01). The results of the six single-arm studies were in accordance with the findings of controlled studies. One controlled and two single-arm studies that evaluated the occurrence of nephrotoxicity reported a pooled incidence rate of 19.2%. Our results suggest that polymyxins may be as efficacious as other antimicrobial therapies for the treatment of carbapenem-resistant Enterobacteriaceae infection. Compared to polymyxin monotherapy, combination regimens may achieve lower 28-day or 30-day mortality. Future large-volume, well-designed randomized control trials are required to determine the role of polymyxins in treating carbapenem-resistant Enterobacteriaceae infections.

Intravenous colistin use for infections due to multidrug-resistant gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis

“…There are however, critical differences between these two studies: in the other study, 247 not all patients were critically ill, MDR pathogens were infrequent, a proportion of 248 patients were receiving systemic colistin for prophylaxis rather than treatment, and the 249 majority of included studies were case reports. In support of our contention that these 250 features may dramatically alter the mortality rates, adults treated with colistin for 251 infections by carbapenem-resistant GNB had rates of clinical cure/improvement and 252 mortality that were more comparable to what we report, with estimated pooled 253 mortality rates between 33.8% -35.7% [28,29]. 254…”

“…We believe that the lower rates of acute kidney injury and 265 neurotoxicity [27] reported in the previous systematic review of colistin use in 266 children are again attributable to the differences in the study characteristics. However, 267 it is worthy to note that the adverse event profile of colistin use in adults is different; 268 in a recent meta-analysis regarding the use of colistin in MDR-GNB infections, 269 colistin-related nephrotoxicity was noted to be much higher (19.2%), while 270 neurotoxicity was not reported [28]. 271…”

Emergence of New Delhi metallo beta lactamase blaNDM-1 and Oxacillinases blaOXA-48 producing Klebsiella pneumoniae in an Egyptian hospital

“…In the present study, Colistin sulfate and polymyxin B showed high antimicrobial activity against almost all CRE isolates, while about 60% were resistant to tigecycline. Resistance of CRE against colistin, tigecycline, and aminoglycosides were reported (Ni et al, 2015). Moreover the percentage of mortality between CRE infected cases that treated by mono-therapy regimens exceeds 40% (Morrill et al, 2015).…”

Multidrug resistant Gram-negative infections in neonatology

“…Colistin in carbapenem-resistant MDRGN infections may or not be combined with another agent, such as carbapenem, ampicillin-sulbactam/ aminoglycosides, depending on each case. 17,18 The experience with the use of fosfomycin in newborn infants is scarce and should be considered as a last resource for children for whom there are no other therapeutic options. The advantage of this broad-spectrum antibiotic is that it has adequate urine, plasma, lung, and cerebrospinal fluid levels and its low toxicity.…”