colistin and Leukopenia

Acinetobacter species are not considered skin commensals and under-treatment is an overriding concern when caring for critically-ill patients who are mostly at risk of extensively drug-resistant Acinetobacter baumannii (XDRAB) infections. Hence even a single blood culture yielding XDRAB will tend to prompt intervention. However, field observations suggest that patients with single-positive blood cultures had milder disease and were more likely to be recruited in interventional studies than those with multiple-positive blood cultures, yet no distinction is made in current clinical or trial recruitment practices. To our knowledge, this is the first study to compare the clinical characteristics and outcomes of patients with single-positive versus multiple-positive blood cultures for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic patients from July 2010 to June 2015, only patients with at least two simultaneously drawn blood cultures were included. The patients were classified as having single-positive or multiple-positive blood cultures according to the number of positive blood cultures yielding XDRAB. The primary end-point was the 28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; P = 0.004), thrombocytopenia (56.0% vs. 26.5%; P < 0.001), higher Pitt bacteremia scores (6.6 vs. 5.5, P = 0.03) and higher 28-day mortality rates (70.9% vs. 43.5%; P = 0.001) distinguished patients with multiple-positive from those with single-positive cultures. Multivariate logistic regression showed that multi-positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34; 95% confidence interval (CI), 1.03-5.28; P = 0.04) and the Cox regression confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13-2.85; P = 0.01) predicted rapid mortality. Patients with multiple versus single positive blood cultures yielding XDRAB had greater morbidity and mortality. Investigators and clinicians should be aware that the blood culture positivity rate impacts outcomes of XDRAB bacteremia.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Blood Culture; Carbapenems; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Humans; Intensive Care Units; Leukopenia; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Severity of Illness Index; Survival Analysis; Thrombocytopenia

Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated.

Topics: Animals; Anti-Bacterial Agents; Body Temperature; Colistin; Cytokines; Edema; Immunoglobulin G; Immunoglobulins, Intravenous; Leukopenia; Lung; Male; Mice; Mice, Inbred ICR; Penicillanic Acid; Peroxidase; Piperacillin; Pneumonia, Bacterial; Pre-Exposure Prophylaxis; Protective Agents; Pseudomonas aeruginosa; Pseudomonas Infections; Tazobactam

Three antimicrobial agents were evaluated as to their ability to neutralize the toxic effects of endotoxin in rabbits. These consisted of two cyclic polypeptides, polymyxin B sulfate and colymycin M (sodium colistimethate), and an aminoglycoside, gentamicin sulfate. Polymyxin B regularly prevented endotoxin-induced leukopenia, thrombocytopenia, and disseminated intravascular coagulation. Colymycin M had similar activity but was not as effective as polymyxin B. Gentamicin demonstrated no neutralizing ability in this study.

Topics: Animals; Colistin; Disseminated Intravascular Coagulation; Endotoxins; Escherichia coli; Gentamicins; Kidney Cortex Necrosis; Leukopenia; Polymyxins; Rabbits; Shwartzman Phenomenon; Thrombocytopenia