RESUMO
Acinetobacter baumannii infection presents a high mortality rate and few therapeutic options. This study aimed to evaluate clinical-microbiological characteristics and prognosis factors of patients diagnosed with A. baumanni. infections treated with oral doxycycline. A retrospective cohort of hospitalized patients with confirmed Acinetobacter spp. infection between 2018 and 2020 receives at least 3 days of oral doxycycline. Clinical and microbiological data were evaluated, including the outcome and molecular characterization of A. baumannii. Doxycycline minimal inhibitory concentrations were evaluated by the broth dilution method. One hundred patients were included with a median age of 51 years. The leading site of infection was pulmonary (n = 62), followed by the soft tissues and skin (n = 28). A. baumannii resistant to carbapenem was found on 94%. The gene blaOXA-23 and blaOXA-51 were amplified in all recovered isolates of A. baumannii (n = 44). Doxycycline MIC50 and MIC90 were 1 µg/mL and 2 µg/mL, respectively. Death rate at 14 days and 28 days of follow-up was 9% and 14%, respectively. The prognostic factors related to death at end of follow-up were age > 49 years [85.7% vs. 46%, CI 95% 6.9 (1.4-32.6), P = 0.015] and hemodialysis [28.6% vs. 7%, CI 95% 5.33 (1.2-22.1), P = 0.021]. Patients treated with doxycycline to A. baumannii presented a relatively low death rate, and risk factors related to death were age and hemodialysis. Further and larger studies should compare polymyxin to doxycycline to better understand the differences between these therapeutic options.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Pessoa de Meia-Idade , Doxiciclina/farmacologia , Doxiciclina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Polimixinas/uso terapêutico , Estudos Retrospectivos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Testes de Sensibilidade Microbiana , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , beta-Lactamases/genéticaRESUMO
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. Meropenemâ+âampicillin/sulbactam was the most frequent combination with synergism (69%), followed by ampicillin/sulbactamâ+âgentamicin (64%) and meropenemâ+âgentamicin (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.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , COVID-19 , Infecções por Acinetobacter/microbiologia , Ampicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Gentamicinas/farmacologia , Humanos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Pandemias , Polimixinas , Sulbactam/farmacologiaRESUMO
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 (AUC24h) 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%.
Assuntos
Ventriculite Cerebral , Infecção Hospitalar , Antibacterianos , Ventriculite Cerebral/induzido quimicamente , Ventriculite Cerebral/tratamento farmacológico , Infecção Hospitalar/induzido quimicamente , Infecção Hospitalar/tratamento farmacológico , Humanos , Unidades de Terapia Intensiva , VancomicinaRESUMO
PURPOSE: The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. METHODS: Intermittent therapy was administered for 60minutes and prescribed as a loading dose of 30mg/kg and continued with 15mg/kg q12h. Continuous infusion was prescribed as a loading dose of 30mg/kg followed by 30mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1h before third dose, 1h, 8h and 24h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1h after loading dose, 12h, 24h, 36h, and 48h after continuous infusion initiation. RESULTS: Median serum concentration of continuous infusion group at 24-hour was 23.59µg/mL [14.52-28.97], while of intermittent infusion group at 23-hour was 12.30µg/mL [7.27-18.12] and on 25-hour was 17.58µg/mL [12.5-22.5]. Medians AUC24-48h were 357.2mg.h/L and 530.2mg.h/L for intermittent infusion and continuous infusion groups, respectively (p=0.559). CONCLUSION: Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.
Assuntos
Antibacterianos/administração & dosagem , Vancomicina/administração & dosagem , Antibacterianos/uso terapêutico , Estado Terminal , Monitoramento de Medicamentos , Humanos , Unidades de Terapia Intensiva , Vancomicina/uso terapêuticoRESUMO
Abstract Purpose The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. Methods Intermittent therapy was administered for 60 minutes and prescribed as a loading dose of 30 mg/kg and continued with 15 mg/kg q12 h. Continuous infusion was prescribed as a loading dose of 30 mg/kg followed by 30 mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1 h before third dose, 1 h, 8 h and 24 h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1 h after loading dose, 12 h, 24 h, 36 h, and 48 h after continuous infusion initiation. Results Median serum concentration of continuous infusion group at 24-hour was 23.59 µg/mL [14.52-28.97], while of intermittent infusion group at 23-hour was 12.30 µg/mL [7.27-18.12] and on 25-hour was 17.58 µg/mL [12.5-22.5]. Medians AUC24-48h were 357.2 mg.h/L and 530.2 mg.h/L for intermittent infusion and continuous infusion groups, respectively (p = 0.559). Conclusion Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.