RESUMO
BACKGROUND: Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO. METHODS: We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI). RESULTS: Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low. CONCLUSIONS: Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.
Assuntos
Osteomielite , Infecções Estafilocócicas , Adulto , Humanos , Rifampina/uso terapêutico , Staphylococcus aureus , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/complicações , Protocolos Clínicos , Osteomielite/tratamento farmacológico , Osteomielite/etiologiaRESUMO
BACKGROUND: Optimal antibiotic dosing for Staphylococcus aureus bloodstream infections (BSI) is still controversial. One reason is inter-individual variation in pharmacokinetics, which may be influenced by various patient-related factors, particularly in critically ill patients. OBJECTIVES: To describe the population pharmacokinetics (PopPK) of the antibiotic flucloxacillin in patients with S. aureus BSI. Subsequently, we sought to translate the model into a user-friendly app for generating a priori and a posteriori time-concentration curves and dose recommendations to optimize dosing regimens. METHODS: Total and unbound flucloxacillin concentrations were included from 49 patients from a prospective cohort study conducted during clinical routine, including non-critically ill and critically ill individuals who received intermittent bolus applications. These data were analysed using non-linear mixed-effects modelling. RESULTS: Most patients (98%) were treated with 2 g of flucloxacillin every 4 h. We developed a joint model that simultaneously described total and unbound concentrations. The model included an allometric effect of glomerular filtration rate on clearance and albumin on the albumin dissociation constant. The latter was especially important, as in our population the unbound fraction was higher at 11.5% (16.7% for critically ill patients) compared with reported values of approximately 5%. Based on our joint model, we developed a web-based app for optimizing dosing regimens of flucloxacillin. CONCLUSIONS: By utilizing data from clinical routine, we were able to create a predictive PopPK model of flucloxacillin and identify influential covariates. The web-based app is currently being validated in a clinical trial.
Assuntos
Antibacterianos , Bacteriemia , Floxacilina , Infecções Estafilocócicas , Humanos , Floxacilina/farmacocinética , Floxacilina/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Idoso , Estudos Prospectivos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Idoso de 80 Anos ou mais , Adulto , Estado Terminal , Infusões IntravenosasRESUMO
In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti-S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS-CoV-2 infection, and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed-effect linear, mixed-effect time-to-event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS-CoV-2 infection (0.89, 95% confidence interval [CI] 0.82-0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53-0.84). In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%-30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti-S1 IgG antibody levels are statistically associated with protection from SARS-CoV-2 infection. However, the prediction impact of the antibody level findings on infection protection is limited.
Assuntos
COVID-19 , Imunoglobulina G , Humanos , Estudos Longitudinais , Estudos de Coortes , Estudos Transversais , Polícia , SARS-CoV-2RESUMO
BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).
Assuntos
Administração Oral , Antibacterianos/administração & dosagem , Doenças Ósseas Infecciosas/tratamento farmacológico , Artropatias/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with ß-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. METHODS: In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS: We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR]â =â 2.15, Pâ =â .03) and antibiotic treatment over 6 weeks (adjusted HRâ =â 0.29, Pâ =â .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment-though not statistically significant for treatment failure (adjusted HRâ =â 0.5, Pâ =â .07) and not for relapses (adjusted HRâ =â 0.5, Pâ =â .10). CONCLUSIONS: We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.
Assuntos
Infecções Relacionadas à Prótese , Rifampina , Idoso , Antibacterianos/uso terapêutico , Desbridamento , Feminino , Humanos , Masculino , Estudos Prospectivos , Infecções Relacionadas à Prótese/tratamento farmacológico , Estudos Retrospectivos , Rifampina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the ß-lactam flucloxacillin are scarce. PATIENTS AND METHODS: We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively. RESULTS: In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01). CONCLUSIONS: Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.
Assuntos
Preparações Farmacêuticas , Sepse , Antibacterianos/efeitos adversos , Estado Terminal , Floxacilina/efeitos adversos , Humanos , Testes de Sensibilidade Microbiana , Probabilidade , Estudos Prospectivos , Sepse/tratamento farmacológico , Staphylococcus aureusRESUMO
BACKGROUND: In non-pregnant adults, the incidence of invasive Group B Streptococcus (GBS) disease is continuously increasing. Elderly and immunocompromised persons are at increased risk of infection. GBS commonly colonizes the vaginal tract, though data on colonization in the elderly are scarce. It is unknown whether the prevalence of GBS colonization is increasing in parallel to the observed rise of invasive infection. We conducted a three-year (2017-2019) prospective observational cross-sectional study in two teaching hospitals in Switzerland to determine the rate of GBS vaginal colonization in women over 60 years and i) to compare the proportions of known risk factors associated with invasive GBS diseases in colonized versus non-colonized women and ii) to evaluate the presence of GBS clusters with specific phenotypic and genotypic patterns in this population. METHODS: GBS screening was performed by using vaginal swabs collected during routine examination from women willing to participate in the study and to complete a questionnaire for risk factors. Isolates were characterized for antibiotic resistance profile, serotype and sequence type (ST). RESULTS: The GBS positivity rate in the elderly was 17% (44/255 positive samples), and similar to the one previously reported in pregnant women (around 20%). We could not find any association between participants' characteristics, previously published risk factors and GBS colonization. All strains were susceptible to penicillin, 22% (8/36) were not susceptible to erythromycin, 14% (5/36) were not susceptible to clindamycin and 8% (3/36) showed inducible clindamycin resistance. Both M and L phenotypes were each detected in one isolate. The most prevalent serotypes were III (33%, 12/36) and V (31%, 11/36). ST1 and ST19 accounted for 11% of isolates each (4/36); ST175 for 8% (3/36); and ST23, ST249 and ST297 for 6% each (2/36). Significantly higher rates of resistance to macrolides and clindamycin were associated with the ST1 genetic background of ST1. CONCLUSIONS: Our findings indicate a similar colonization rate for pregnant and elderly women. TRIAL REGISTRATION: Current Controlled Trial ISRCTN15468519 ; 06/01/2017.
Assuntos
Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificação , Vagina/microbiologia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Estudos Transversais , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Gravidez , Prevalência , Estudos Prospectivos , Sorogrupo , Infecções Estreptocócicas/epidemiologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/genética , Suíça/epidemiologiaRESUMO
BACKGROUND: Streptococcal infections are associated with life-threatening pneumonia and sepsis. The rise in antibiotic resistance calls for novel approaches to treat bacterial diseases. Anti-virulence strategies promote a natural way of pathogen clearance by eliminating the advantage provided to bacteria by their virulence factors. In contrast to antibiotics, anti-virulence agents are less likely to exert selective evolutionary pressure, which is a prerequisite for the development of drug resistance. As part of their virulence mechanism, many bacterial pathogens secrete cytolytic exotoxins (hemolysins) that destroy the host cell by destabilizing their plasma membrane. Liposomal nanotraps, mimicking plasmalemmal structures of host cells that are specifically targeted by bacterial toxins are being developed in order to neutralize-by competitive sequestration-numerous exotoxins. RESULTS: In this study, the liposomal nanotrap technology is further developed to simultaneously neutralize the whole palette of cytolysins produced by Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis-pathogens that can cause life-threatening streptococcal toxic shock syndrome. We show that the mixture of liposomes containing high amounts of cholesterol and liposomes composed exclusively of choline-containing phospholipids is fully protective against the combined action of exotoxins secreted by these pathogens. CONCLUSIONS: Unravelling the universal mechanisms that define targeting of host cells by streptococcal cytolysins paves the way for a broad-spectrum anti-toxin therapy that can be applied without a diagnostic delay for the treatment of bacterial infections including those caused by antibiotic-resistant pathogens.
Assuntos
Lipossomos/farmacologia , Lipossomos/uso terapêutico , Infecções Estreptocócicas/tratamento farmacológico , Antibacterianos/uso terapêutico , Toxinas Bacterianas , Diagnóstico Tardio , Proteínas Hemolisinas , Humanos , Streptococcus , Streptococcus pyogenesRESUMO
Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 µg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (r = 0.37, P < 0.001) and were significantly lower when tocilizumab was preadministered. No correlation was found between HCQ concentrations and CRP values. High LPV plasma concentrations were observed in COVID-19 patients. The ratio of calculated unbound drug fraction to published SARS-CoV-2 50% effective concentrations (EC50) indicated insufficient LPV concentrations in the lung. CRP values significantly correlated with LPV but not HCQ plasma concentrations, implying inhibition of cytochrome P450 3A4 (CYP3A4) metabolism by inflammation.
Assuntos
Antivirais/farmacocinética , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Hidroxicloroquina/farmacocinética , Lopinavir/farmacocinética , Pneumonia Viral/tratamento farmacológico , Ritonavir/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/sangue , Antivirais/farmacologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Esquema de Medicação , Combinação de Medicamentos , Feminino , Hospitais Universitários , Humanos , Hidroxicloroquina/sangue , Hidroxicloroquina/farmacologia , Tempo de Internação/estatística & dados numéricos , Lopinavir/sangue , Lopinavir/farmacologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Ritonavir/sangue , Ritonavir/farmacologia , SARS-CoV-2 , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
Rifampin has been used as an agent in combination therapy in orthopedic device-related infections (ODRI) for almost three decades. The aim of this review is to provide data regarding the role of rifampin against biofilm infection in vitro, in animal models, and in clinical ODRI. Available data are gathered in order to present the rational use of rifampin combinations in patients with periprosthetic joint infection (PJI). The role of rifampin is well defined in patients with PJI and is indicated in those who fulfill the Infectious Diseases Society of America criteria for debridement and implant retention or one-stage exchange. It should be used with care because of the danger of rapid emergence of resistance. Potential drug interactions should be considered.
Assuntos
Biofilmes/efeitos dos fármacos , Rifampina/farmacologia , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Rifampina/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidadeRESUMO
A pan-susceptible Salmonella enterica serovar Worthington isolate was detected in the stool of a man returning from Sri Lanka. Under ceftriaxone treatment, a third-generation cephalosporin (3GC)-resistant Salmonella Worthington was isolated after 8 days. Molecular analyses indicated that the two isolates were identical. However, the latter strain acquired a blaDHA-1-carrying IncFII plasmid probably from a Citrobacter amalonaticus isolate colonizing the gut. This is the first report of in vivo acquisition of plasmid-mediated resistance to 3GCs in S. enterica.
Assuntos
Cefalosporinas/farmacologia , Plasmídeos/genética , Salmonella/efeitos dos fármacos , Salmonella/genética , Resistência às Cefalosporinas/genética , Citrobacter/efeitos dos fármacos , Citrobacter/genética , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade MicrobianaRESUMO
PURPOSE OF REVIEW: Systemic antibiotic therapy in persons with a diabetic foot infection (DFI) is frequent, increasing the risk of promoting resistance to common pathogens. Applying principles of antibiotic stewardship may help avoid this problem. RECENT FINDINGS: We performed a systematic review of the literature, especially seeking recently published studies, for data on the role and value of antibiotic stewardship (especially reducing the spectrum and duration of antibiotic therapy) in community and hospital populations of persons with a DFI. SUMMARY: We found very few publications specifically concerning antibiotic stewardship in persons with a DFI. The case-mix of these patients is substantial and infection plays only one part among several chronic problems. As with other types of infections, attempting to prevent infections and avoiding or reducing the spectrum and duration of antibiotic therapy are perhaps the best ways to reduce antibiotic prescribing in the DFI population. The field is complex and necessitates knowledge over the current scientific literature and clinical experience. On a larger scale, clinical pathways, guidelines, and recommendations are additionally supportive.
Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/métodos , Pé Diabético/tratamento farmacológico , Prescrições de Medicamentos/normas , HumanosRESUMO
AIM: To assess amoxicillin-clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO). METHODS: We performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases. RESULTS: The median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days). Oral AMC was prescribed for a median of 20 days (interquartile range, 12-30 days). The median ratio of oral AMC among the entire antibiotic treatment was 0.9 (interquartile range, 0.7-1.0). After a median follow-up of 3.3 years, 178 DFIs (22%) overall recurred (DFO, 75; 22%). Overall, oral AMC led to 74% remission compared with 79% with other regimens (χ2 -test; P = 0.15). In multivariate analyses and stratified subgroup analyses, oral AMC resulted in similar clinical outcomes to other antimicrobial regimens, when used orally from the start, after an initial parenteral therapy, or when prescribed for DFO. CONCLUSIONS: Oral AMC is a reasonable option when treating patients with DFIs and DFOs.
Assuntos
Combinação Amoxicilina e Clavulanato de Potássio , Antibacterianos , Pé Diabético/tratamento farmacológico , Administração Oral , Idoso , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Pé Diabético/complicações , Pé Diabético/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Cefepime monitoring in urine by micellar electrokinetic capillary chromatography with UV detection and liquid chromatography coupled to mass spectrometry via electrospray ionization is described. For micellar electrokinetic capillary chromatography, sample preparation comprised urine dilution and dodecyl-sulfate protein precipitation at pH 4.5, whereas diluted urines were analyzed in the other assay. Both approaches provided suitable conditions for cefepime analysis in urines of healthy volunteers that were spiked with cefepime. Cefepime monitoring by micellar electrokinetic capillary chromatography in samples from patients taking multiple drugs were prone to interferences, whereas liquid chromatography coupled to mass spectrometry provided clean chromatograms and thus selective detection of cefepime in all samples. The latter assay was used to measure urinary cefepime in a prospective pilot study and to assess cefepime stability in urines at 25, 4, -20 and -70°C. The data suggest that urinary cefepime is stable for at least 72 h at all tested temperatures.
RESUMO
BACKGROUND.: Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. METHODS.: A retrospective, observational, multicenter, international study was performed during 2003-2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. RESULTS.: Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using ß-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%-46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with ß-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). CONCLUSIONS.: This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of ß-lactams are confirmed and maybe also a potential benefit from adding rifampin.
Assuntos
Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/terapia , Infecções Relacionadas à Prótese/terapia , Infecções Estreptocócicas/terapia , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Artrite Infecciosa/microbiologia , Artrite Infecciosa/mortalidade , Biofilmes/efeitos dos fármacos , Desbridamento , Feminino , Humanos , Internacionalidade , Masculino , Prognóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/mortalidade , Estudos Retrospectivos , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Terapia de Salvação , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus agalactiae/isolamento & purificação , Falha de Tratamento , beta-Lactamas/administração & dosagem , beta-Lactamas/uso terapêuticoRESUMO
Gene mutations in the virulence regulator CovR/S of group A Streptococcus play a substantial role in the pathogenesis of streptococcal toxic shock syndrome. We screened 25 group B Streptococcus (GBS) isolates obtained from patients with streptococcal toxic shock syndrome and found only 1 GBS clone harboring this kind of mutation.
Assuntos
Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Mutação , Proteínas Repressoras/genética , Choque Séptico/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/patogenicidade , Fatores de Virulência/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/metabolismo , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Proteínas Repressoras/metabolismo , Sorotipagem , Choque Séptico/mortalidade , Choque Séptico/patologia , Infecções Estreptocócicas/mortalidade , Infecções Estreptocócicas/patologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/genética , Análise de Sobrevida , Virulência , Fatores de Virulência/metabolismoRESUMO
Each year in the United States, 500 patients are hospitalized for cat-scratch disease, caused by Bartonella henselae infection. We report a case of rare but serious neurologic B. henselae infection. When typical features of cat-scratch disease occur with neurologic findings, Bartonella infection should be suspected and diagnostic testing should be performed.
Assuntos
Bartonella , Doença da Arranhadura de Gato/complicações , Mielite Transversa/etiologia , Anti-Infecciosos/uso terapêutico , Doença da Arranhadura de Gato/líquido cefalorraquidiano , Doença da Arranhadura de Gato/tratamento farmacológico , Doença da Arranhadura de Gato/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mielite Transversa/líquido cefalorraquidiano , Mielite Transversa/tratamento farmacológicoRESUMO
OBJECTIVES: Group B Streptococcus (GBS) increasingly causes invasive disease in non-pregnant adults, particularly in elderly persons and those with underlying diseases. Combination therapy with penicillin plus gentamicin has been suggested for periprosthetic joint infection. The postulated synergism of this combination is based on experiments with planktonic bacteria. We aimed to assess the efficacy of this combination against sessile bacteria. METHODS: Four different GBS strains were used. We compared results of MICs with those of minimal biofilm eradication concentrations (MBECs), applied chequerboard assays to the MBEC device and calculated the fractional inhibitory concentration index. Synergism was evaluated with time-kill assays against bacteria adherent to cement beads, using penicillin (0.048, 0.2 and 3â mg/L), gentamicin (4 and 12.5â mg/L) and a combination thereof. Results were evaluated via colony counting after sonication of beads and scanning electron microscopy. RESULTS: MBEC/MIC ratios were 2000-4000 for penicillin and 1-4 for gentamicin. In chequerboard assays, synergism was observed in all four isolates. In time-kill assays, penicillin and 12.5â mg/L gentamicin showed synergism in two isolates. In the other two isolates 12.5â mg/L gentamicin alone was as efficient as the combination therapy. CONCLUSIONS: These in vitro investigations show activity of 12.5â mg/L gentamicin, alone or as an adjunct to penicillin, against four strains of biofilm GBS. This concentration cannot be achieved in bone with systemic administration, but can be reached if administered locally. The combination of systemic penicillin plus local gentamicin indicates a potential application in orthopaedic-device-associated GBS infections. Studies with a larger number of strains are required to confirm our results.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Gentamicinas/farmacologia , Penicilinas/farmacologia , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/fisiologia , Contagem de Colônia Microbiana , Quimioterapia Combinada/métodos , Humanos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Osteoartrite/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológicoRESUMO
Cefepime monitoring in deproteinized human serum and plasma by micellar electrokinetic capillary chromatography and liquid chromatography coupled to mass spectrometry in presence of other drugs is reported. For micellar electrokinetic capillary chromatography, sample preparation comprised dodecylsulfate protein precipitation at pH 4.5 using an increased buffer concentration compared to that of a previous assay and removal of hydrophobic compounds with dichloromethane. This provided robust conditions for cefepime analysis in the presence of sulfamethoxazole and thus enabled its determination in samples of patients that receive cotrimoxazole. The liquid chromatography assay is based upon use of a column with a pentafluorophenyl-propyl modified and multiendcapped stationary phase and the coupling to electrospray ionization with a single quadrupole detector. The performances of both assays with multilevel internal calibration were assessed with calibration and control samples and both assays were determined to be robust. Cefepime levels monitored by micellar electrokinetic capillary chromatography in samples from patients that were treated with cefepime only and with cefepime and cotrimoxazole were found to compare well with those obtained by liquid chromatography coupled to mass spectrometry. Cefepime drug levels determined by micellar electrokinetic capillary chromatography could thereby be validated.
Assuntos
Cefalosporinas/sangue , Cromatografia Capilar Eletrocinética Micelar , Cefepima , Cromatografia Líquida , Humanos , Espectrometria de MassasRESUMO
Streptococcus agalactiae (group B Streptococcus [GBS]) is a leading cause of sepsis in neonates. The rate of invasive GBS disease in nonpregnant adults also continues to climb. Aminoglycosides alone have little or no effect on GBS, but synergistic killing with penicillin has been shown in vitro. High-level gentamicin resistance (HLGR) in GBS isolates, however, leads to the loss of a synergistic effect. We therefore performed a multicenter study to determine the frequency of HLGR GBS isolates and to elucidate the molecular mechanisms leading to gentamicin resistance. From eight centers in four countries, 1,128 invasive and colonizing GBS isolates were pooled and investigated for the presence of HLGR. We identified two strains that displayed HLGR (BSU1203 and BSU452), both of which carried the aacA-aphD gene, typically conferring HLGR. However, only one strain (BSU1203) also carried the previously described chromosomal gentamicin resistance transposon designated Tn3706. For the other strain (BSU452), plasmid purification and subsequent DNA sequencing resulted in the detection of plasmid pIP501 carrying a remnant of a Tn3 family transposon. Its ability to confer HLGR was proven by transfer into an Enterococcus faecalis isolate. Conversely, loss of HLGR was documented after curing both GBS BSU452 and the transformed E. faecalis strain from the plasmid. This is the first report showing plasmid-mediated HLGR in GBS. Thus, in our clinical GBS isolates, HLGR is mediated both chromosomally and extrachromosomally.