Early dynamic changes to monocytes following major surgery are associated with subsequent infections.

Background: Post-operative infections are a common cause of morbidity following major surgery. Little is understood about how major surgery perturbs immune function leading to heightened risk of subsequent infection. Through analysis of paired blood samples obtained immediately before and 24 h following surgery, we evaluated changes in circulating immune cell phenotype and function across the first 24 h, to identify early immune changes associated with subsequent infection. Methods: We conducted a prospective observational study of adult patients undergoing major elective gastrointestinal, gynecological, or maxillofacial surgery requiring planned admission to the post-anesthetic care unit. Patients were followed up to hospital discharge or death. Outcome data collected included mortality, length of stay, unplanned intensive care unit admission, and post-operative infections (using the standardized endpoints in perioperative medicine-core outcome measures for perioperative and anesthetic care criteria). Peripheral blood mononuclear cells were isolated prior to and 24 h following surgery from which cellular immune traits including activation and functional status were assessed by multi-parameter flow cytometry and serum immune analytes compared by enzyme-linked immunosorbent assay (ELISA). Results: Forty-eight patients were recruited, 26 (54%) of whom developed a post-operative infection. We observed reduced baseline pre- and post-operative monocyte CXCR4 and CD80 expression (chemokine receptors and co-stimulation markers, respectively) in patients who subsequently developed an infection as well as a profound and selective post-operative increase in CD4+ lymphocyte IL-7 receptor expression in the infection group only. Higher post-operative monocyte count was significantly associated with the development of post-operative infection (false discovery rate < 1%; adjusted p-value = 0.001) with an area under the receiver operating characteristic curve of 0.84 (p < 0.0001). Conclusion: Lower monocyte chemotaxis markers, higher post-operative circulating monocyte counts, and reduced co-stimulatory signals are associated with subsequent post-operative infections. Identifying the underlying mechanisms and therapeutics to reverse defects in immune cell function requires further exploration.

Mortality and clinical cure rates for pneumonia: a systematic review, meta-analysis, and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments.

BACKGROUND: Bactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia. OBJECTIVES: We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates. DATA SOURCES: PubMed, Cochrane Library, Embase, and MedRxiv STUDY ELIGIBILITY CRITERIA: Randomized control trials. PARTICIAPANTS: Adult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital. INTERVENTIONS: Bacteriostatic versus bactericidal antibiotics. ASSESSMENT OF RISK OF BIAS: The Cochrane Collaboration assessing risk of bias 2 tool. METHODS OF DATA SYNTHESIS: Data on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel-Haenszel method was used for integrating RRs for generalizability of findings. The I2 method was used to assess the magnitude of variation secondary to heterogeneity. RESULTS: Forty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99-1.05; I2: 37%; TSA-adjusted CI, 0.99-1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81-1.42; I2: 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97-1.03; I2: 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83-1.11; I2: 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50-2.63; I2: 0%) were similar between bactericidal and bacteriostatic antibiotic treatments. CONCLUSIONS: Bactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia.