The most important condition for the successful treatment of sepsis is the optimal antibiotic therapy prescribed in a timely manner. It is possible that combination therapy

Β-lactam + aminoglycoside has certain advantages compared to monotherapy with only β-lactam.

The objective of the Cochrane meta-analysis published in 2014 was to study the efficacy of β-lactam as monotherapy compared to the combined treatment of β-lactam + aminoglycoside in patients with sepsis, as well as to assess the frequency of adverse events when applying the studied treatment regimens, including such an undesirable phenomenon as the formation of antibiotic resistance in microorganisms.

Studies were searched for in the Cochrane Central Register of Controlled Trials (CENTRAL, number 11, 2013), the MEDLINE databases (from 1966 to November 4, 2013); EMBASE (from 1980 to November 2013); LILACS (from 1982 to November 2013), as well as in the documents presented to the Interscience Conference on Antimicrobial Agents and Chemotherapy for the period from 1995 to 2013.

One meta-analysis included randomized and pseudo-randomized trials that compared monotherapy with β-lactam antibiotics to a β-lactam + aminoglycoside combination in sepsis.

The primary outcome measure assessed was mortality for all reasons. Secondary endpoints were treatment failure, development of secondary infection and adverse events. Two experts independently collected and evaluated the relevance of the studies to be included in the meta-analysis.

The meta-analysis included 69 studies in which 7863 patients participated. In 22 studies, the same β-lactam was compared in the two groups and in the other studies, different β-lactams were compared (as a rule, β-lactam antibiotics with a wider spectrum of activity were used in the monotherapy group).

It turned out that in studies comparing the same β-lactams, there was no difference between the groups compared in terms of mortality for all reasons (relative risk 0.97, 95% confidence interval 0.73-1.3) and the development of clinical ineffective treatment (relative risk 1.11, 95% CI 0.95-1.29).

In studies comparing different β-lactams (1), there was a tendency to decrease mortality for all reasons in patients receiving β-lactam monotherapy (relative risk 0.85, 95% CI 0.71 -1.01) and (2) significant differences were found in the frequency of development of clinical treatment failure - less in the monotherapy group (relative risk 0.75, 95% CI 0.67-0 , 84). There were no statistically significant differences in the subgroups, including in patients with infections caused by Gram-negative pathogens. The group of patients with infections caused by Pseudomonas aeruginosa has not been properly evaluated due to insufficient capacity (sample size). Differences in mortality rates were described as low level of evidence, mainly due to possible error. The results of the clinical ineffectiveness of the therapy were also qualified as a low level of evidence due to the indirectness of the result and the occurrence of a possible systematic error associated with the establishment of the result in studies without blind people.

There was no difference between the groups compared in the frequency of development of antibiotic resistance in pathogens during treatment. Nephrotoxicity occurred significantly less frequently in the monotherapy group (relative risk 0.30, 95% CI 0.23-0.39). In these comparisons, no heterogeneity was detected.

A small number of studies were included in the meta-analysis, in which the pathogens were Gram-positive pathogens, primarily related to infectious endocarditis. In these studies, there was also no difference between monotherapy and combination therapy.

Thus, according to the results of a meta-analysis, the addition of aminoglycosides to β-lactams for the treatment of sepsis is not recommended, since the mortality rate remains unchanged for all reasons, and the risk of nephrotoxicity increases significantly.