Background: This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis.Methods: This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose.Results: Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5-0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6-138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC 24h ) was 838 mg*h/L (515-1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95-12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47-42.1), and median CSF/ serum ratio was 18.6% (8.4-41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004).Conclusions: Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.

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Background During the COVID-19 pandemic, the burden of nosocomial infections caused by MDR pathogens has caused a shortage of polymyxins. Thus, we evaluated the in vitro synergism and antibiofilm activity of antimicrobial combinations and propose a test kit for synergism against carbapenem-resistant Acinetobacter baumannii (CRAB). Methods Fifty-six CRAB isolates were tested for synergy between meropenem, gentamicin and ampicillin/sulbactam. MICs were determined by broth microdilution. Synergism was tested using chequerboard analysis, followed by a time–kill curve. Additionally, minimum biofilm eradication concentration was determined and the antibiofilm activity of the combinations was evaluated by MTT assay and biomass reduction. A test kit was developed for routine laboratory testing to detect synergism. Results All CRAB isolates were resistant to gentamicin and ampicillin/sulbactam. Chequerboard synergism occurred against 75% of the isolates. Meropenem + ampicillin/sulbactam was the most frequent combination with synergism (69%), followed by ampicillin/sulbactam + gentamicin (64%) and meropenem + gentamicin (51%). All combinations presented only bacteriostatic activity and no bactericidal or antibiofilm effects. The routine laboratory test showed 100% accuracy compared with other in vitro assays. Conclusions Our study demonstrates the potential role of antibiotic combinations against planktonic bacteria. In vitro synergism is possible and can be an alternative treatment for patients with CRAB infection during a polymyxin shortage.

Purpose:Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics–pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures.Methods:A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole.Results:TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays.Conclusions:TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.

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Introdução Durante a pandemia de COVID-19, a carga de infecções adquiridas em hospitais causadas por patógenos multirresistentes causou uma escassez de polimixinas. Além disso, as infecções hospitalares causadas por microrganismos resistentes demonstraram ser um fator importante relacionado ao mau prognóstico. O objetivo deste estudo foi avaliar o sinergismo in vitro e a atividade anti-biofilme de combinações de antimicrobianos, e propor um kit de teste de sinergismo para Acinetobacter baumannii resistente a carbapenêmicos (CRAB). Métodos Cinquenta e seis isolados de CRAB foram testados quanto ao sinergismo com meropenem, gentamicina e ampicilina / sulbactam. As concentrações inibitórias mínimas (CIM) foram determinadas por microdiluição em caldo. O sinergismo foi testado por checkerboard, seguido pela curva de tempo-morte (time kill-curve - TKC). Além disso, a concentração mínima de erradicação de biofilme (MBEC) foi determinada, e a atividade antibiofilme das combinações foi avaliada por ensaio de viabilidade celular (MTT) e redução de biomassa (retenção de cristal violeta). Resultados Todos os CRABs eram resistentes à gentamicina e ampicilina / sulbactam. Sinergia em checkerboard ocorreu em 75%. Meropenem + ampicilina / sulbactam foi a combinação mais frequente com sinergismo (69%), seguido de ampicilina / sulbactam + gentamicina (64%) e meropenem + gentamicina (51%). Todas as combinações apresentaram apenas atividade bacteriostática, sem efeito bactericida ou anti-biofilme. No entanto, o sinergismo avaliado com TKC mostrou uma potente atividade de meropenem + gentamicina em um teste isolado com uma redução de carga bacteriana superior a 2log em duas horas, mas com crescimento a partir de 24h. O teste de rotina laboratorial apresenta 100% de acurácia com os demais ensaios in vitro. Conclusões Nosso estudo demonstrou um papel potencial das combinações para as bactérias planctônicas. O sinergismo in vitro é possível e pode ser uma alternativa de tratamento em pacientes com infecção por CRAB durante uma escassez de polimixina. No entanto, as combinações de antibióticos analisados não foram bactericidas, mas podem ser uma alternativa em infecções com baixas cargas bacterianas.