In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae

ABSTRACT The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing K. pneumoniae is dependent on polymyxin B susceptibility. Further in vitro and animal studies must be performed to fully evaluate the efficacy of this drug combination

História Natural Da Disseminação De Enterobactérias Produtoras De Carbapenemases Em Um Hospital Cirúrgico Terciário.

After The Introduction Of Carbapenem Resistant Klebsiella Pnemoniae (Kp-Kpc) In A Tertiary Hospital For Cardiovascular Surgeries And Heart Transplantations, This Microorganism Spread Within The Hospital Environment. Objectives: To Evaluate The Epidemiological, Molecular And Clinical Aspects Related To Mediastinitis Due To Carbapenem-Resistant Enterobacteriacea (Cre) In A Single And Closed Environment During A Five-Year Period. Methods: We Evaluated The Kp-Kpc Cluster Pattern At All Units At The Dante Pazzanese Cardiology Institute, Sp, From June 2009 To June 2014 Using Traditional Active Surveillance Methods And Retrospective Space-Time Permutation Model. All Isolates Had Their Identification Confirmed By Maldi-Tof Ms Method And Were Submitted To Molecular Characterization By Real-Time Pcr For Esbl And Kpc Genes And By Pulsed Field Gel Electrophoresis (Pfge) And By Mlst For Clonal Similarity. Also, We Evaluated The Clinical And Therapeutic Aspects Related To Polymyxin And Aminoglycosides Combinations In RespeApós A Introdução De Klebsiella Pnemoniae Resistente Aos Carbapenêmicos (Kp- Kpc), Em Um Hospital Destinado A Cirurgias Cardiovasculares, Terciário, Proveniente De Um Paciente Internado Para Avaliação De Transplante Cardíaco, Ocorreu Uma Disseminação Deste Microrganismo No Ambiente Hospitalar. Objetivos: Avaliar Os Aspectos Epidemiológicos, Moleculares E Clínicos Referentes À Mediatinite Por Enterobactérias Resistentes Aos Carbapenêmicos (Cre) Em Ambiente Único E Fechado Por Um Período De Cinco Anos. Métodos: Foram Avaliados Os Padrões De Cluster Kp-Kpc Em Todas As Unidades Do Instituto Dante Pazzanese De Cardiologia De São Paulo, Sp, De Junho De 2009 A Junho De 2014 Usando Métodos Tradicionais De Vigilância Ativa E O Modelo Retrospectivo De Permutação Espaço-Temporal. Todos Os Isolados Tiveram Sua Identificação Confirmada Pelo Método Matrix-Assisted Laser Desorption/Ionization (Maldi-Tof Ms) E Foram Submetidos À Caracterização Molecular Por Polymerase Chain Reaction (Pcr) Em Tempo Real Para Genes Esbl E CarbDados abertos - Sucupira - Teses e dissertações (2018

Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis

A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides or polymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%) patients. The median time to acute kidney injury was 6.0 (95% CI 3-14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6-42) days in the polymyxin with other antimicrobial combinations group (p = 0.03). Polymyxin B with aminoglycosides group progressed faster to any degree of renal dysfunction. (C) 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo FAPESPInst Dante Pazzanese Cardiol, Sao Paulo, SP, BrazilUniv North Carolina Chapel Hill, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USAHosp Clin Porto Alegre, Serv Doencas Infecciosas, Porto Alegre, RS, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Sao Paulo, SP, BrazilFAPESP: 2108-3/2014Web of Scienc

Aspergillus infection in the ascending aorta of a patient with aortic and mitral valve prostheses

We report the case of implantation of metallic mitral and aortic valve prostheses 6 months earlier, with subsequent multiple embolic episodes. The anatomicopathological examination of the thrombus of the third embolic episode was compatible with Aspergillus sp, which was treated with amphotericin B, followed by oral itraconazole. On the fourth embolism, vegetations were visualized in the ascending aorta on echocardiography and resonance imaging, and the patient underwent replacement of the aortic segment by a Haemashield tube and exploration of the aortic prosthesis, which was preserved, because no signs of endocarditis were found. Four months later, the patient died due to cardiogenic shock secondary to acute myocardial infarction caused by probable coronary embolism and partial dysfunction of the aortic prosthesis

Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis

A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides orpolymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%)patients. The median time to acute kidney injury was 6.0 (95% CI 3–14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6–42) days in the polymyxinwith other antimicrobial combinations group (p = 0.03). Polymyxin B with aminoglycosidesgroup progressed faster to any degree of renal dysfunction

Effect of polymyxin B-containing regimens on renal function for the treatment of carbapenem-resistant Enterobacteriacea mediastinitis

A retrospective cohort study, were evaluated: polymyxin B plus aminoglycosides orpolymyxin B plus other antibiotics. Any degree of acute kidney injury occurred in 26 (86.6%)patients. The median time to acute kidney injury was 6.0 (95% CI 3–14) days in the polymyxin-aminoglycoside containing regimen group, against 27.0 (95% CI 6–42) days in the polymyxinwith other antimicrobial combinations group (p = 0.03). Polymyxin B with aminoglycosidesgroup progressed faster to any degree of renal dysfunction

Nosocomial infections caused by Elizabethkingia meningoseptica: an emergent pathogen

We hereby describe the clinical and epidemiological features and, outcomes of nine patients with Elizabethkingia meningoseptica infections in two hospitals over a 2-year period. All infections caused by this pathogen were nosocomial, or healthcare associated infections, in hemodialysis settings whereas none was correlated with hospital outbreaks

Long term mortality of deep sternal wound infection after coronary artery bypass surgery Mortalidade em longo prazo da infecção esternal profunda após cirurgia de revascularização do miocárdio

BACKGROUND: Deep sternal wound infection and mediastinitis determine high in-hospital mortality. International studies show that these patients are also at increased cardiovascular mortality risk in long-term follow-up. However, data are scarce and there is no national data. OBJECTIVES: The aim of this study is to evaluate the mortality and incidence of cardiovascular events in long-term follow-up of patients suffering from deep sternal wound infection and mediastinitis. METHODS: Case-control study, matched by propensity score in a 1:1 proportion, in patients submitted to coronary artery bypass grafting between 2005 and 2008 at the Institute Dante Pazzanese of Cardiology (São Paulo, SP, Brazil). The primary outcome was death. As a secondary outcome, we analyzed the composite event of myocardial infarction, new revascularization, stroke or death. RESULTS: Of 1975 patients, 114 developed one of the infections. During the mean follow up of 3.6 years, deep sternal wound infection and mediastinitis increased the risk of death by 8.26 (95% CI 1.88-36.29, P = 0.005) and the incidence of combined end point by 2.61 (95% CI 1.2-5.69, P = 0.015). The Kaplan-Meier curves for both outcomes demonstrated that the greatest risk occurs in the first six months, followed by a period of stabilization and further increase in the incidence of events after 4 years of hospital discharge. The similarity between the curves of primary and secondary outcomes may be consequent to the predominance of death on the combined cardiovascular events. CONCLUSION: The presence of deep sternal wound infection or mediastinitis increased mortality in long-term follow-up in this sample of the Brazilian population according to the same pattern displayed by the developed countries.<br>INTRODUÇÃO: A infecção esternal profunda e a mediastinite determinam elevada mortalidade intra-hospitalar. Estudos prévios demonstram que esses pacientes também apresentam maior mortalidade cardiovascular em longo prazo. No entanto, os dados são escassos para o Brasil. OBJETIVO: O objetivo deste estudo é avaliar a mortalidade e a incidência de eventos cardiovasculares em longo prazo em pacientes acometidos de infecção esternal profunda e mediastinite. MÉTODOS: Estudo de caso-controle com pareamento 1:1 por meio de propensity score, em pacientes submetidos à cirurgia de revascularização do miocárdio entre 2005 e 2008, no Instituto Dante Pazzanese de Cardiologia (São Paulo, SP, Brasil). O desfecho primário avaliado foi óbito. Como desfecho secundário, analisou-se o composto de infarto agudo do miocárdio, nova revascularização miocárdica, acidente vascular encefálico ou óbito. RESULTADOS: De 1975 pacientes avaliados, 114 desenvolveram infecção esternal profunda ou mediastinite. Durante o seguimento médio de 3,6 anos, as infecções conferiram razão de risco de óbito de 8,26 (IC 95% 1,88-36,29, P = 0,005), tendo sido a razão de risco de desfecho combinado de 2,61 (IC 95% 1,2-5,69, P = 0,015). A curva de Kaplan-Meier para ambos os desfechos demonstra que o maior risco ocorre nos primeiros 6 meses, seguindo-se um período de estabilização e novo aumento na incidência de eventos após 4 anos da alta hospitalar. A semelhança entre as curvas dos desfechos primário e secundário pode ser consequente à predominância do óbito sobre os demais eventos cardiovasculares. CONCLUSÃO: A presença de infecção esternal profunda ou de mediastinite aumentou a mortalidade em longo prazo nesta amostra da população brasileira, de acordo com o mesmo padrão exibido nos países desenvolvidos