We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue.

Controversy surrounds combination treatment or monotherapy against multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Acinetobacter infections in clinical practice. We searched the PubMed and Scopus databases for studies reporting on the clinical outcomes of patients infected with MDR, XDR, and PDR Acinetobacter spp. with regard to the administered intravenous antibiotic treatment. Twelve studies reporting on 1,040 patients suffering from 1,044 infectious episodes of MDR Acinetobacter spp. were included. The overall mortality between studies varied from 28.6 to 70 %; from 25 to 100 % in the monotherapy arm and from 27 to 57.1 % in the combination arm. Combination treatment was superior to monotherapy in three studies, where carbapenem with ampicillin/sulbactam (mortality 30.8 %, p = 0.012), carbapenem with colistin (mortality 23 %, p = 0.009), and combinations of colistin with rifampicin, sulbactam with aminoglycosides, tigecycline with colistin and rifampicin, and tigecycline with rifampicin and amikacin (mortality 27 %, p < 0.05) were used against MDR Acinetobacter spp. resistant at least to carbapenems. The benefit was not validated in the remaining studies. Clinical success varied from 42.4 to 76.9 % and microbiological eradication varied from 32.7 to 67.3 %. Adverse events referred mainly to polymixins nephrotoxicity that varied from 19 to 50 %. The emergence of resistance was noted with tigecycline regimens in off-label uses in three studies. The available data preclude a firm recommendation with regard to combination treatment or monotherapy. For the time being, combination treatment may be preferred for severely ill patients. We urge for randomized controlled trials examining the optimal treatment of infections due to MDR, XDR, and PDR Acinetobacter spp.

Data originating from a small number of African countries suggest that the proportion of ESBL-producing isolates among Enterobacteriaceae may not be high in Africa, but is certainly not negligible. Further studies are needed from countries where no or limited relevant data are available.