RESUMO
We report a 15 year-old Nigerian adolescent male with chronic osteomyelitis caused by an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain of sequence type 773 (ST773) carrying blaNDM-1 and an extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae strain. The patient developed neurological side effects in the form of circumoral paresthesia with polymyxin B and asymptomatic elevation of transaminases with aztreonam (used in combination with ceftazidime-avibactam). Cefiderocol treatment for 14 weeks plus bone implantation resulted in apparent cure and avoided amputation.
Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Ensaios de Uso Compassivo/métodos , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Adolescente , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Nigéria , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Resistência beta-Lactâmica/genética , beta-Lactamases/genética , CefiderocolRESUMO
BACKGROUND: The Clinical and Laboratory Standards Institute (CLSI) revised cefepime interpretive criteria, introducing the susceptible dose-dependent category for Enterobacteriaceae with a minimum inhibitory concentration (MIC) of 4 to 8 µg/mL in 2014. Limited clinical data support these new categories. This study compares outcomes of patients treated with standard and high-dose cefepime across various MICs. METHODS: We retrospectively reviewed cases of pneumonia or bacteremia caused by gram-negative organisms treated with adequate doses of cefepime for ≥48 hours. Outcomes were compared for MICs of ≤2 (low), 4 (medium), and 8 µg/mL (high). The primary end point was clinical failure, the secondary end point was microbiological failure. RESULTS: Ninety cases met the inclusion criteria: 46, 25, and 19 patients with low, medium, or high MIC, respectively. Multivariate logistic regression revealed that the medium (odds ratio [OR]: 9.13, P < .01) and high (OR: 6.79, P = .01) MIC groups had increased clinical failure. CONCLUSION: Cefepime therapy, even at CLSI-recommended doses, had an increased risk of clinical failure for gram-negative pathogens with MICs of 4 or 8 µg/mL. This finding suggests that higher dosing regimens (2 g every 8 hours or 1 g every 6 hours) may be necessary to treat serious gram-negative infections with elevated MICs.
Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Adulto , Idoso , Antibacterianos/farmacologia , Cefepima , Cefalosporinas/farmacologia , Estudos de Coortes , Relação Dose-Resposta a Droga , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We report a case of infective endocarditis (IE) caused by ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant S. aureus (MRSA). Resistance to ceftaroline emerged in the absence of drug exposure, and the E447K substitution in the active site of PBP2a previously associated with ceftaroline resistance was identified. Additionally, we present evidence of patient-to-patient transmission of the strain within the same unit. This case illustrates the difficulties in treating MRSA IE in the setting of a multidrug-resistant phenotype.
Assuntos
Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Daptomicina/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Endocardite Bacteriana/tratamento farmacológico , Proteínas de Ligação às Penicilinas/genética , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico , Adulto , Substituição de Aminoácidos , Cefalosporinas/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Infecção Hospitalar/patologia , Quimioterapia Combinada , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/patologia , Expressão Gênica , Humanos , Masculino , Meticilina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , CeftarolinaRESUMO
Vancomycin is the first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, but its efficacy in adult patients has been questioned. Less is known about the outcomes of MRSA bacteremia treated with vancomycin in pediatric patients. This study reviews the outcomes and clinical characteristics of MRSA bacteremia in children treated with vancomycin and characterizes the microbiologic and molecular features of the bloodstream isolates. A retrospective cohort study was conducted among pediatric patients with MRSA bacteremia treated with vancomycin for >5 days from 1 August 2005 to 31 May 2007 in a large tertiary care center. MRSA bloodstream isolates were characterized by antimicrobial susceptibility testing, PCR analysis of virulence genes, and Diversilab typing. Clinical records were reviewed for outcomes and comorbidities. A total of 22 pediatric patients with MRSA bacteremia were identified. Eleven cases (50.0%) were considered vancomycin treatment failures. Features significantly associated with vancomycin treatment failure were prematurity (P = 0.02) and isolates positive for Panton-Valentine leukocidin (PVL) (P = 0.008). Features typically associated with community-associated MRSA strains were identified in hospital-associated isolates. A dominant clone was not responsible for the high number of treatment failures. Further studies are needed to determine if vancomycin should be the first-line treatment for MRSA bacteremia in premature infants and for PVL-positive isolates.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/patologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Vancomicina/uso terapêutico , Adolescente , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Criança , Pré-Escolar , Estudos de Coortes , Impressões Digitais de DNA , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Fatores de Virulência/genéticaRESUMO
A patient with native valve endocarditis caused by a vancomycin "heteroresistant" strain of Enterococcus faecium experienced failure of daptomycin monotherapy without evidence of daptomycin resistance. The infecting organism exhibited in vivo emergence of a vancomycin-susceptible subpopulation lacking vanA. Treatment with a combination of high-dose daptomycin, gentamicin, and high-dose ampicillin cleared the infection.
Assuntos
Daptomicina/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Enterococcus faecium/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Resistência a Vancomicina/genética , Ampicilina/uso terapêutico , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/genética , DNA Bacteriano/genética , Quimioterapia Combinada , Enterococcus faecium/genética , Enterococcus faecium/isolamento & purificação , Gentamicinas/uso terapêutico , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Família Multigênica , Falha de TratamentoRESUMO
Increasing resistance in Pseudomonas aeruginosa to multiple antibiotics has been observed and is posing therapeutic dilemmas. Antibiotic utilization is one factor that has been associated with the emergence of antimicrobial resistance. We examined the overall and specific antimicrobial use in relation to changes in susceptibility patterns in P. aeruginosa. Regression analysis was performed to explore the relationships between annual antibiotic use and the incidence of resistant P. aeruginosa. There were statistically significant relationships between increasing anti-pseudomonal cephalosporin and levofloxacin use and the increasing incidence of ciprofloxacin resistant P. aeruginosa. However, there was not an association between other fluoroquinolone or overall fluoroquinolone use and this change. In addition, there was no association between increasing anti-pseudomonal cephalosporin use and cefepime resistant P. aeruginosa. No statistical relationship was seen with overall antibiotic use and the development of resistance in P. aeruginosa, suggesting that the development of resistance is associated with the use of individual agents, rather than overall antibiotic consumption.