RESUMO
BACKGROUND: Ertapenem, a long-acting carbapenem, may be an alternative to the recommended prophylactic antibiotic cefotetan. METHODS: In this randomized, double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis with ertapenem, as compared with cefotetan, in patients undergoing elective colorectal surgery. A successful outcome was defined as the absence of surgical-site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively. All adverse events were collected until 14 days after the administration of antibiotic prophylaxis. RESULTS: Of the 1002 patients randomly assigned to study groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group and 334 in the cefotetan group) were included in the per-protocol analysis. After adjustment for strata, in the modified intention-to-treat analysis, the rate of overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1 to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%; 95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the superiority of ertapenem. In the modified intention-to-treat analysis, the most common reason for failure of prophylaxis in both groups was surgical-site infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population, the overall incidence of Clostridium difficile infection was 1.7% in the ertapenem group and 0.6% in the cefotetan group (P=0.22). CONCLUSIONS: Ertapenem is more effective than cefotetan in the prevention of surgical-site infection in patients undergoing elective colorectal surgery but may be associated with an increase in C. difficile infection. (ClinicalTrials.gov number, NCT00090272 [ClinicalTrials.gov].).
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Cefotetan/uso terapêutico , Cirurgia Colorretal , Infecção da Ferida Cirúrgica/prevenção & controle , beta-Lactamas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Antibacterianos/efeitos adversos , Cefotetan/administração & dosagem , Cefotetan/efeitos adversos , Clostridioides difficile , Infecções por Clostridium , Método Duplo-Cego , Procedimentos Cirúrgicos Eletivos , Ertapenem , Feminino , Humanos , Infusões Intravenosas , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Falha de Tratamento , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversosRESUMO
Scoring the severity of a diabetic foot wound infection may help assess the severity, determine the type and urgency of antibiotic and surgical treatment needed, and predict clinical outcomes. We developed a 10-item diabetic foot infection wound score (results could range from 3 to 49 [least to most severe]) incorporating semi-quantitative grading of both wound measurements and various infection parameters. Using data from a prospective diabetic foot infection antibiotic trial (SIDESTEP), we evaluated the score's accuracy in predicting outcome, analyzed its components and tested it for consistency, construct, and validity. Wound scores for 371 patients significantly correlated with the clinical response; it was favorable at the follow-up assessment in 94.8% with a baseline score =12 compared with 77.0% with a score >19. Scores demonstrated good internal consistency (Cronbach's alpha >0.70 to <0.95). Patients with more severe wounds had higher scores, supporting construct validity. Excluding scores for wound discharge (purulent and nonpurulent), leaving an eight-item score, provided better measurement statistics. This easily performed wound score appears to be a reliable, valid, and useful tool for predicting clinical outcomes. Further validation studies in different patient populations should refine the items included.
Assuntos
Pé Diabético/diagnóstico , Infecções/diagnóstico , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de RiscoRESUMO
BACKGROUND: A randomized study comparing single-dose cefotetan and ertapenem prophylaxis for elective colorectal surgery in 1,002 patients found ertapenem to be significantly more effective (p < 0.001). Failures of prophylaxis were thought to involve organisms resistant to both antimicrobial agents, isolated most often from deep or superficial incision sites. METHODS: Further testing and analysis of the microbial data was performed. Susceptibility results were correlated with the clinical outcomes reported previously. RESULTS: Of the 216 aerobes tested, 62.6% were resistant to cefotetan and 44% to ertapenem. Enterococci and methicillin-resistant Staphylococcus epidermidis were the aerobes recovered most frequently, and Bacteroides thetaiotaomicron, Clostridium innocuum, and Eubacterium lentum were the most frequent anaerobes. Enterococcus faecalis usually was associated in mixed culture with Bacteroides fragilis group species. Approximately one-half of the 158 anaerobes (50.7%), including all the species above, were resistant to cefotetan; most of these (61.4%) came from superficial incision sites. Only one anaerobe (Desulfovibrio fairfieldensis), found in a superficial incisional infection, was resistant to ertapenem, and no ertapenem-resistant enteric bacteria were recovered. In vitro resistance was associated with therapeutic failure. CONCLUSIONS: The in vitro activity of ertapenem was superior to that of cefotetan against all anaerobic and many aerobic bacteria isolated from postoperative cultures of patients who failed prophylaxis with these agents. Our findings help to elucidate the results of the clinical trial.
Assuntos
Antibioticoprofilaxia , Bactérias/efeitos dos fármacos , Cefotetan/uso terapêutico , Colo/cirurgia , Reto/cirurgia , Infecção da Ferida Cirúrgica/microbiologia , beta-Lactamas/uso terapêutico , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Anaeróbias/efeitos dos fármacos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Cefotetan/farmacologia , Procedimentos Cirúrgicos Eletivos , Ertapenem , Humanos , Testes de Sensibilidade Microbiana , Infecção da Ferida Cirúrgica/epidemiologia , Falha de Tratamento , beta-Lactamas/farmacologiaRESUMO
BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) is examining aerobic and facultatively anaerobic gram-negative bacilli (GNB) isolated from intra-abdominal infections. This report summarizes the 2005 annual data. METHODS: During 2005, 76 medical centers in 31 countries in five regions collected intra-abdominal GNB for antimicrobial susceptibility testing using broth microdilution according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: A total of 5,476 unique aerobic and facultatively anaerobic GNB were isolated. Enterobacteriaceae accounted for 86% (4,711) of the total isolates. Among the 12 antimicrobial agents tested, the carbapenems and amikacin were the most reliably active against the Enterobacteriaceae, whereas ampicillin/sulbactam most often was the least active. Escherichia coli was the species most commonly isolated, at 48% (2,654). Extended-spectrum beta-lactamases (ESBLs) were detected phenotypically in 12% (325/2,329) of E. coli and 18% (151/856) of Klebsiella spp. In general, ESBL producers demonstrated lower susceptibility to the majority of the antibiotics than the non-producers; however, ESBL producers usually were susceptible to the carbapenems tested. CONCLUSIONS: In 2005, antibiotic resistance continued to be a problem among GNB isolated from intra-abdominal infections, with the highest resistance rates observed in the Asia/Pacific region. Imipenem-cilastatin, ertapenem, and amikacin were the agents most consistently active in vitro against the Enterobacteriaceae isolated.
Assuntos
Cavidade Abdominal/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Bactérias Aeróbias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Bacilos Gram-Negativos Anaeróbios Facultativos/efeitos dos fármacos , Enterobacteriaceae/efeitos dos fármacos , Saúde Global , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Vigilância da População , Resistência beta-LactâmicaRESUMO
BACKGROUND: The effectiveness of prophylactic antibiotics in the prevention of surgical site infection (SSI) after elective colorectal surgery is dependent on many factors, including the body mass index (BMI) of the patient. In this study, the association of BMI and type of antibiotic prophylaxis with SSI was evaluated in patients undergoing elective colorectal surgery. METHOD: A post-hoc analysis was performed using data obtained from a multicenter randomized, double-blind study of 1,002 patients undergoing elective colorectal surgery who received prophylactic administration of ertapenem (1 g) or cefotetan (2 g). Among 650 evaluable patients, the effect of BMI and type of antibiotic prophylaxis on SSI rates was assessed four weeks after surgery. Mechanical bowel preparation was standardized, and no patient received oral antibiotics; intravenous antibiotics were not repeated during or after surgery. RESULTS: The majority of patients had a BMI between 18.5 and 39.9 kg/m2. Regardless of the type of prophylaxis, SSI rates were significantly higher in patients with a BMI > or = 30 kg/m2 than in those with a BMI < 30 kg/m2. However, failure, defined as SSI, was significantly less common after ertapenem than after cefotetan prophylaxis at both BMI < 30 kg/m2 (12.7% vs. 26.4%, respectively; difference -13.7; 95% confidence interval [CI] -21.0, -6.5) and BMI > or = 30 kg/m2 (26.7% vs. 41.9%, respectively; difference -15.3; 95% CI -28.2, -2.0). The most prevalent type of SSI was superficial incisional infection, which was more common with both treatments in patients with a BMI > or = 30 kg/m2; however, the incidence of superficial SSI was lower after ertapenem than cefotetan prophylaxis. CONCLUSION: In patients undergoing elective colorectal surgery, the incidence of SSI, specifically superficial incisional SSI, was higher in patients with a BMI > or = 30 kg/m2, regardless of the prophylactic antibiotic given. Ertapenem prophylaxis was more effective than cefotetan in the prevention of SSI at any BMI.
Assuntos
Antibioticoprofilaxia , Cefotetan/uso terapêutico , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Obesidade/fisiopatologia , Infecção da Ferida Cirúrgica/prevenção & controle , beta-Lactamas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Colo/cirurgia , Ertapenem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reto/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: The costs of treating surgical site infections can be considerable. There is a cost associated with the prophylactic use of antibiotics; however, the use of prophylactic agents may reduce infection rates and lengths of stay, thus offsetting the overall treatment cost and potentially generating cost savings to hospitals. This project was intended to determine the potential cost impact of using ertapenem 1 g vs. cefotetan 2 g as prophylaxis for elective colorectal surgery. METHODS: Cost analysis using efficacy data from the PREVENT clinical trial and drug acquisition and total hospital costs in 2005 dollars from Premier's Perspective Comparative Database in patients > or = 18 year of age, evaluable at four weeks after elective surgery of the colon or rectum and prophylactic treatment with ertapenem (n = 338) or cefotetan (n = 334). The primary outcome measures were the rate of prophylactic drug failure and the difference between the ertapenem and cefotetan groups in costs related to and total hospital stay. Prophylactic failure was defined as a surgical site infection, unexplained antibiotic use, or anastomotic leak. RESULTS: Prophylactic failure occurred in 28.1% of the patients receiving ertapenem and 42.8% of those receiving cefotetan (p < 0.05). The most common prophylactic failure was surgical site infection: 18.3% for ertapenem, 31.1% for cefotetan, difference (95% confidence interval) -13.0% (-19.5, -6.5%) (p < 0.05). The mean +/- standard deviation length of stay for all patients, including prophylactic successes and failures, was 7.6 +/- 6.6 days for ertapenem and 8.7 +/- 9.5 days for cefotetan. The mean per-patient cost of prophylactic drugs and hospital room and board was $15,245 with ertapenem and $17,428 cefotetan, a net difference of -$2,181. CONCLUSIONS: Ertapenem used in prophylaxis for elective colorectal operations results in a lower rate of surgical site infection and a shorter average length of stay than cefotetan. The calculated net difference in prophylactic antibiotic drug and hospital costs represents a saving of $2,181 per patient with ertapenem relative to cefotetan.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Cefotetan/uso terapêutico , Cirurgia Colorretal/efeitos adversos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , beta-Lactamas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/economia , Antibioticoprofilaxia/economia , Antibioticoprofilaxia/estatística & dados numéricos , Cefotetan/economia , Análise Custo-Benefício , Ertapenem , Feminino , Custos Hospitalares , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/economia , Falha de Tratamento , Resultado do Tratamento , beta-Lactamas/economiaRESUMO
BACKGROUND: Increasing nosocomial pathogen resistance to available antimicrobial agents is of growing concern. While higher MICs can diminish antimicrobial effectiveness, dose adjustments often mitigate this effect. This study's objective was to ascertain whether MICs among major pathogens in the ICU to several commonly used agents have increased enough to significantly impact their ability to achieve bactericidal effect. METHODS: Cefepime, ceftriaxone, imipenem and piperacillin-tazobactam MICs were determined with 74,394 Gram-negative bacilli obtained from ICU patients with various infections in the US between 1993 and 2004. Results were grouped into four 3-year periods. The predicted cumulative fraction of response (CFR) was estimated based on patient-derived pharmacokinetic values and Monte Carlo simulation. Trends in CFR over the four study periods were assessed using the Cochran-Armitage test. The primary analysis included all organisms combined; Pseudomonas aeruginosa and Acinetobacter species were also evaluated individually. RESULTS: In the primary analysis, imipenem 500 mg q6h showed CFRs from 87% to 90% across all four study periods, with a trend toward slightly improved bactericidal target attainment (p < 0.01). CFRs for cefepime 2 g q12h and piperacillin-tazobactam 4.5 g q6h both declined by 2% (p < 0.01 and p < 0.05, respectively), reflecting upward shifts in the underlying MIC distributions. Ceftriaxone had <52% CFR for all regimens in all periods, with no significant trend. Against P. aeruginosa, significant declines in CFR were seen for (range, p-value): imipenem 1 g q8h (82%-79%, p < 0.01), cefepime 1 g q12h (70%-67%, p < 0.01), cefepime 2 g q12h (84%-82%, p < 0.05), piperacillin-tazobactam 3.375 g q6h (76%-73%, p < 0.01), piperacillin-tazobactam 4.5 g q8h (71%-68%, p < 0.01), and piperacillin-tazobactam 4.5 g q6h (80%-77%, p < .01). Against Acinetobacter spp., all regimens of imipenem, cefepime and piperacillin-tazobactam showed significant declines in CFR over time (p < 0.01). CONCLUSION: Our observations suggest that as a result of increasing antimicrobial resistance among ICU pathogens in the US, drug effectiveness, assessed as a function of individual agents' ability to attain pharmacodynamic targets, has declined, especially with P. aeruginosa and Acinetobacter spp. Cefepime 2 g q8h and imipenem were the most potent agents against these species, respectively. More aggressive dosing of all of the agents characterized could preserve their clinical utility, but this must be balanced with safety and tolerability issues by the physician.
Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , beta-Lactamas/farmacologia , Antibacterianos/farmacocinética , Humanos , Unidades de Terapia Intensiva , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Estados UnidosRESUMO
BACKGROUND: Complicated intra-abdominal infections are a common problem in surgical practice. This study compared the effectiveness of ertapenem (1 g qd) and piperacillin/tazobactam (3.375 g q6h) in the treatment of these infections. METHODS: This was a multicenter, double-blinded, randomized study conducted in patients with complicated intra-abdominal infections. Of the 535 patients screened, 500 were stratified on the basis of disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score < or =10 or >10), then randomized (1:1) to 4-14 days of treatment with one of the regimens and six weeks of followup. Nearly all patients (N = 494) were treated. The primary endpoint was the proportion of microbiologically evaluable patients with a favorable clinical response (cure) at two weeks. Non-inferiority of ertapenem was based on a difference in response rate of <15 percentage points compared with piperacillin/tazobactam (lower bound of the 95% CI > -15). RESULTS: Of the 494 treated patients, 231 were microbiologically evaluable, with 123 and 108 patients in the ertapenem and piperacillin/tazobactam groups, respectively. Statistically similar cure rates were observed in the ertapenem (82.1%) and piperacillin/tazobactam (81.7%) groups (difference 0.3 [95% CI: -9.6, 10.5]). The pathogens isolated most frequently were Escherichia coli, Bacteroides fragilis, and Bacteroides thetaiotamicron, typical isolates associated with intra-abdominal infections. There were no statistical differences between the groups in serious drug-related clinical adverse events, drug-related clinical adverse experiences leading to study discontinuation, or mortality. CONCLUSIONS: Ertapenem was non-inferior to piperacillin/tazobactam in the cure of intra-abdominal infections caused by susceptible pathogens. Both study drugs generally were well tolerated.
Assuntos
Abscesso Abdominal/tratamento farmacológico , Peritonite/tratamento farmacológico , beta-Lactamas/efeitos adversos , beta-Lactamas/uso terapêutico , APACHE , Abscesso Abdominal/complicações , Abscesso Abdominal/microbiologia , Abscesso Abdominal/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Bacteroides/isolamento & purificação , Método Duplo-Cego , Ertapenem , Escherichia coli/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Peritonite/complicações , Peritonite/microbiologia , Peritonite/mortalidade , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , beta-Lactamas/administração & dosagemRESUMO
PURPOSE: To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin-tazobactam given every six hours daily in treating diabetic foot infections. METHODS: A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment (n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam ($13.58), (b) average U.S. wages and benefits for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose. RESULTS: There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin-tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections. CONCLUSION: A CMA of treatment of diabetic foot infections showed that, compared with piperacillin-tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.
Assuntos
Antibacterianos/economia , Infecções Bacterianas/tratamento farmacológico , Pé Diabético/tratamento farmacológico , beta-Lactamas/economia , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Bacterianas/complicações , Pé Diabético/complicações , Esquema de Medicação , Combinação de Medicamentos , Ertapenem , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/economia , Ácido Penicilânico/uso terapêutico , Piperacilina/administração & dosagem , Piperacilina/economia , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , beta-Lactamas/administração & dosagem , beta-Lactamas/uso terapêuticoRESUMO
BACKGROUND: Diabetic foot infections are a common and serious problem, yet few randomised trials of adequate quality have compared the efficacy of the various antibiotic regimens available for their treatment. Our aim was to assess the efficacy and safety of ertapenem versus piperacillin/tazobactam for foot infections. METHODS: We did a randomised, double-blinded, multicentre trial in adults (n=586) with diabetes and a foot infection classified as moderate-to-severe and requiring intravenous antibiotics. We assigned patients intravenous ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3.375 g every 6 h; n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators retained the option to administer vancomycin to patients in either group to ensure adequate coverage for potentially antibiotic resistant Enterococcus spp and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was the proportion of patients with a favourable clinical response (cure or improvement) on the day that intravenous antibiotic was discontinued. Analyses were by an evaluable-patient only approach. This study is registered with , number NCT00229112. FINDINGS: Of the 576 patients treated, 445 were available for assessment at the end of intravenous therapy. Both baseline characteristics and favourable clinical response rates were similar for the 226 who received ertapenem and the 219 who received piperacillin/tazobactam (94%vs 92%, respectively; between treatment difference 1.9%, 95% CI -2.9 to 6.9). Rates of favourable microbiological responses (eradication rates and clinical outcomes, by pathogen) and adverse events did not differ between groups. INTERPRETATION: Clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam, suggesting that this once-daily antibiotic should be considered for parenteral therapy of diabetic foot infections, when deemed appropriate.
Assuntos
Antibacterianos/uso terapêutico , Pé Diabético/tratamento farmacológico , beta-Lactamas/uso terapêutico , Adulto , Idoso , Pé Diabético/classificação , Pé Diabético/microbiologia , Método Duplo-Cego , Esquema de Medicação , Ertapenem , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
HYPOTHESIS: Anastomotic leaks following elective colorectal resections increase morbidity, mortality, and the need for additional interventions. An accurate understanding of risk factors would potentially reduce anastomotic leaks and/or allow appropriate selection of patients for diverting stomas. DESIGN: Prospective review of patient and operative characteristics that contribute to anastomotic leaks. SETTING: Fifty-one sites within the United States (May 2002-March 2005). PATIENTS: Six hundred seventy-two patients who participated in a trial comparing preoperative antimicrobials in elective open colorectal surgery. MAIN OUTCOME MEASURES: Anastomotic leaks were diagnosed using clinical findings and were confirmed with imaging. We examined 20 variables possibly affecting anastomotic healing in univariate and multivariate analyses. RESULTS: There were 24 anastomotic leaks in 672 patients (3.6%) undergoing elective colorectal resection. There were 10 deaths (1.5%). A baseline albumin level of less than 3.5 g/dL (to convert to grams per liter, multiply by 10) (P = .04) and male sex (P = .03) were associated with anastomotic leaks in both univariate and multivariate analyses (adjusted odds ratios, 2.56 and 3.12, respectively). Increased duration of surgery (SD, 60 minutes; odds ratio, 1.53; 95% confidence interval, 1.06-2.22; P = .03) and steroid use at the time of surgery (odds ratio, 3.85; 95% confidence interval, 1.24-11.93; P = .02) were significant in univariate analysis. Surgical procedure with rectal resection; prophylaxis with ertapenem (vs cefotetan); or history of obesity, tobacco use, or diabetes was not associated with anastomotic leaks. CONCLUSIONS: Significant risk factors for anastomotic leaks include low preoperative serum albumin level, steroid use, male sex, and increased duration of surgery. Appreciation of risk factors provides a rational basis for temporary diversion.
Assuntos
Colectomia/efeitos adversos , Idoso , Anastomose Cirúrgica , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Cefotetan/uso terapêutico , Colectomia/métodos , Procedimentos Cirúrgicos Eletivos , Ertapenem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Albumina Sérica/análise , beta-Lactamas/uso terapêuticoRESUMO
To aid clinicians in selecting the appropriate approach for treating patients with diabetic foot infections, we investigated whether any baseline clinical findings predicted an unfavourable clinical outcome. Using data from a large, prospective treatment trial of diabetic foot infections (SIDESTEP), we assessed the association between clinical treatment failure and baseline history, physical and laboratory findings, by univariate and multivariate logistic regression analyses. Among 402 patients clinically evaluable 10 days after completing antibiotic therapy, baseline factors significantly (P < 0.05) associated by univariate analysis with treatment failure were 'severe' (versus 'moderate') University of Texas (UT) wound grade; elevated white blood cell count, C-reactive protein or erythrocyte sedimentation rate; high wound severity score; inpatient treatment; low serum albumin; male sex; and skin temperature of affected foot >10 degrees C above that of unaffected foot. By multivariate logistic regression only severe UT wound grade (odds ratio 2.1) and elevated white blood cell count [odds ratio 1.7 for a 1 standard deviation (2971 cells/mm(3)) increase] remained statistically significant. Clinical failure rates were 46% for patients with both risk factors compared with 10% for patients with no risk factors and 16-17% for patients with one risk factor. Increased white blood cell count and severe UT wound grade at baseline, but not other features, were significant independent and additive risk factors for clinical failure in patients treated for a diabetic foot infection.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Antibacterianos/uso terapêutico , Pé Diabético/classificação , Pé Diabético/microbiologia , Ertapenem , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Índice de Gravidade de Doença , Falha de Tratamento , beta-Lactamas/uso terapêuticoRESUMO
As part of a United States-based multicenter clinical trial, conducted from 2001 to 2004, that compared ertapenem to piperacillin-tazobactam for the treatment of moderate-to-severe diabetic foot infections (DFIs), we obtained 454 pretreatment specimens from 433 patients. After debridement, the investigators collected wound specimens, mostly by curettage or biopsy, and sent them to the R. M. Alden Research Laboratory for aerobic and anaerobic culture. Among the 427 positive cultures, 83.8% were polymicrobial, 48% grew only aerobes, 43.7% had both aerobes and anaerobes, and 1.3% had only anaerobes. Cultures yielded a total of 1,145 aerobic strains and 462 anaerobic strains, with an average of 2.7 organisms per culture (range, 1 to 8) for aerobes and 2.3 organisms per culture (range, 1 to 9) for anaerobes. The predominant aerobic organisms were oxacillin-susceptible Staphylococcus aureus (14.3%), oxacillin-resistant Staphylococcus aureus (4.4%), coagulase-negative Staphylococcus species (15.3%), Streptococcus species (15.5%), Enterococcus species (13.5%), Corynebacterium species (10.1%), members of the family Enterobacteriaceae (12.8%), and Pseudomonas aeruginosa (3.5%). The predominant anaerobes were gram-positive cocci (45.2%), Prevotella species (13.6%), Porphyromonas species (11.3%), and the Bacteroides fragilis group (10.2%). Pure cultures were noted for 20% of oxacillin-resistant Staphylococcus aureus cultures, 9.2% of Staphylococcus epidermidis cultures, and 2.5% of P. aeruginosa cultures. Two or more species of Staphylococcus were present in 13.1% of the patients. Ertapenem and piperacillin-tazobactam were each active against >98% of the enteric gram-negative rods, methicillin-sensitive S. aureus, and anaerobes. Among the fluoroquinolones, 24% of anaerobes, especially the gram-positive cocci, were resistant to moxifloxacin; 27% of the gram-positive aerobes but only 6% of the members of the family Enterobacteriaceae were resistant to levofloxacin. Moderate-to-severe DFIs are typically polymicrobial, and almost half include anaerobes. Our antibiotic susceptibility results can help to inform therapeutic choices.
Assuntos
Anti-Infecciosos/farmacologia , Bactérias Aeróbias/efeitos dos fármacos , Bactérias Aeróbias/isolamento & purificação , Bactérias Anaeróbias/efeitos dos fármacos , Bactérias Anaeróbias/isolamento & purificação , Pé Diabético/microbiologia , Adulto , Anti-Infecciosos/uso terapêutico , Farmacorresistência Bacteriana , Feminino , Humanos , Masculino , Testes de Sensibilidade MicrobianaRESUMO
During the 12-year period from 1993 to 2004, antimicrobial susceptibility profiles of 74,394 gram-negative bacillus isolates recovered from intensive care unit (ICU) patients in United States hospitals were determined by participating hospitals and collected in a central location. MICs for 12 different agents were determined using a standardized broth microdilution method. The 11 organisms most frequently isolated were Pseudomonas aeruginosa (22.2%), Escherichia coli (18.8%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (9.1%), Acinetobacter spp. (6.2%), Serratia marcescens (5.5%), Enterobacter aerogenes (4.4%), Stenotrophomonas maltophilia (4.3%), Proteus mirabilis (4.0%), Klebsiella oxytoca (2.7%), and Citrobacter freundii (2.0%). Specimen sources included the lower respiratory tract (52.1%), urine (17.3%), and blood (14.2%). Rates of resistance to many of the antibiotics tested remained stable during the 12-year study period. Carbapenems were the most active drugs tested against most of the bacterial species. E. coli and P. mirabilis remained susceptible to most of the drugs tested. Mean rates of resistance to 9 of the 12 drugs tested increased with Acinetobacter spp. Rates of resistance to ciprofloxacin increased over the study period for most species. Ceftazidime was the only agent to which a number of species (Acinetobacter spp., C. freundii, E. aerogenes, K. pneumoniae, P. aeruginosa, and S. marcescens) became more susceptible. The prevalence of multidrug resistance, defined as resistance to at least one extended-spectrum cephalosporin, one aminoglycoside, and ciprofloxacin, increased substantially among ICU isolates of Acinetobacter spp., P. aeruginosa, K. pneumoniae, and E. cloacae.
Assuntos
Infecção Hospitalar/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Unidades de Terapia Intensiva , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla , Fluoroquinolonas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Fatores de Tempo , Estados UnidosRESUMO
BACKGROUND: The type of mechanical bowel preparation (MBP) used before elective colorectal surgery remains controversial. METHODS: This post hoc analysis of a prospective randomized controlled antibiotic prophylaxis trial (ertapenem vs. cefotetan) evaluated the effect of polyethylene glycol (PEG) and sodium phosphate (SP) MBPs on the rates of postoperative surgical site infections (SSI). RESULTS: Good to excellent MBPs were observed in 281 of 303 (93%) evaluable patients for the PEG and 336 of 367 (92%) for the SP types. A higher rate of SSI was observed in the PEG (34%) than SP (24%) group (difference, 10%; 95% confidence interval, 3.4-17.2). The MBP type was a significant risk factor for SSI, with SP favored over PEG (odds ratio, .6; 95% confidence interval, .43-.85) in univariate analysis; multivariate analysis favored SP, but was not significant (odds ratio, .69; 95% confidence interval, .46-1.02). SSI was lowest with SP and ertapenem (19%) and highest with PEG and cefotetan (44%). CONCLUSIONS: SP, coupled with ertapenem antibiotic prophylaxis, may improve outcomes and reduce SSIs in patients undergoing elective colorectal surgery when compared with PEG coupled with cefotetan antibiotic prophylaxis.
Assuntos
Catárticos/uso terapêutico , Colectomia/efeitos adversos , Fosfatos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Cefotetan/uso terapêutico , Colo/cirurgia , Ertapenem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Ensaios Clínicos Controlados Aleatórios como Assunto , Reto/cirurgia , Infecção da Ferida Cirúrgica/etiologia , beta-Lactamas/uso terapêuticoRESUMO
The purpose of the study was to assess in patients with a diabetic foot infection (DFI), whether differences in skin temperature of the affected foot as compared to the corresponding site on the contralateral foot using dermal thermometry (DT) correlates with infection severity and clinical outcome. As part of the SIDESTEP DFI study, investigators took DT measurements at baseline and the discontinuation of intravenous therapy (DCIV) and performed a systematic evaluation of the infected limb to calculate a wound score. We compared the skin temperature differential between the limbs at the two assessments and determined the correlation between this value and surrogate markers of inflammation and the clinical response to treatment. Among patients enrolled in SIDESTEP, 332 were fully evaluable. The mean temperature differential between the limbs was 2.81 +/- 5.75 degrees F at baseline and 2.43 +/- 4.84 degrees F at DCIV (mean change: -0.37; 95% confidence interval (CI): -0.98, 0.23; P= 0.225). Skin temperature differential at baseline did not correlate with white blood cell count, level of C-reactive protein or erythrocyte sedimentation rate or the infection severity score (r= 0.058, 0.148, -0.002, 0.067, respectively). We observed no overall trend between surface temperature differential at baseline and clinical outcome at DCIV, but patients with a skin temperature differential of > or =10 degrees F at baseline had a significantly lower clinical response than those whose differential was <10 degrees F (81.4% versus 94.3%; difference 12.9%; 95% CI: 3.5, 27.3%, P= 0.007). While there was no overall relationship between skin temperature and poor clinical outcome, there may be a threshold effect in DT (<10 degrees F versus >10 degrees F) between the limbs at baseline that predicts outcome of therapy.
Assuntos
Pé Diabético/fisiopatologia , Infecções/diagnóstico , Temperatura Cutânea/fisiologia , Termografia/métodos , Pé Diabético/complicações , Progressão da Doença , Seguimentos , Humanos , Infecções/fisiopatologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Bowel colonization with resistant bacteria can develop in patients receiving broad-spectrum antimicrobial therapy. We compared the impact of two antimicrobial regimens often used to treat intraabdominal infections on susceptibility patterns of bowel flora at the end of therapy. In a double-blind clinical trial, adults with complicated intraabdominal infection requiring surgery were randomized to receive piperacillin-tazobactam (3.375 g every 6 h) or ertapenem (1 g once a day) for 4 to 14 days. Rectal swabs were obtained at baseline and at the end of study therapy to determine the acquisition rates of Enterobacteriaceae resistant to the study drug, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella species, Pseudomonas aeruginosa resistant to imipenem or piperacillin-tazobactam, and vancomycin-resistant Enterococcus faecalis or Enterococcus faecium. Treated patients were assessable for the acquisition of resistant bacteria if appropriate specimens were obtained at both time points. Enterobacteriaceae resistant to the treatment received were acquired during study therapy by 8/122 assessable piperacillin-tazobactam recipients (6.6%) compared to 0/122 assessable ertapenem recipients (P = 0.007). Neither ESBL-producing E. coli or Klebsiella species nor P. aeruginosa resistant to piperacillin-tazobactam was isolated from patients in either treatment group. Imipenem-resistant P. aeruginosa was acquired by two of the ertapenem recipients (1.6%) versus zero of the piperacillin-tazobactam recipients (P = 0.50). Vancomycin-resistant enterococci were acquired during therapy by 8/125 assessable ertapenem recipients (6.4%) versus 2/123 assessable piperacillin-tazobactam recipients (1.6%; P = 0.10). In this study, the acquisition of resistant Enterobacteriaceae occurred significantly more often in patients treated with piperacillin-tazobactam than in those treated with ertapenem.
Assuntos
Abscesso Abdominal/microbiologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Quimioterapia Combinada/uso terapêutico , Lactamas/uso terapêutico , Reto/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/crescimento & desenvolvimento , Ertapenem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Resultado do Tratamento , beta-LactamasRESUMO
Human immunodeficiency virus (HIV) patients on nucleoside or nucleotide reverse transcriptase inhibitors with HIV RNA at <1,000 copies/ml were randomized in an open-label study to administration of combined indinavir/ritonavir (IDV/RTV) at 667/100 mg every 12 h (q12h) or IDV alone at 800 mg q8h to determine the regimens' pharmacokinetics. On day 14, plasma IDV and RTV levels were determined over 24 h. Noncompartmental pharmacokinetics (minimum concentration of drug in serum [C(min)], area under the concentration-time curve from 0 to 24 h [AUC(0-24)], and maximum concentration of drug in serum [C(max)]) were expressed as geometric mean values with 90% confidence intervals (CI). The primary hypothesis was that the lower bound of the protocol-specified 90% CI for the geometric mean C(min) ratio of the combination compared to IDV alone regimen would be >/=2. Twenty-seven patients were enrolled, and 24 (15 male; average age, 42 years) completed the study. The C(min), AUC(0-24), and C(max) for IDV/RTV compared to IDV alone were 1,511 versus 250 nM, 119,557 versus 77,034 nM . h, and 10,428 versus 10,407 nM, respectively. Corresponding relationships for IDV/RTV compared to IDV alone were a 6.0-fold increase in C(min) (90% CI, 4.0, 9.3), an increase in AUC(0-24) (1.5-fold, 90% CI, 1.2, 2.0), and no increase in C(max). Adverse events were similar and generally mild, with no cases of nephrolithiasis. The geometric mean ratio of IDV C(min) for IDV/RTV compared to IDV was at least 2 by a lower bound of the 90% CI, satisfying the primary hypothesis. The C(max) was not increased, suggesting an IDV/RTV 667/100-mg toxicity profile may be similar to that of unboosted IDV.