A pharmacodynamic strategy to optimize empirical antibiotic therapy for gram-negative bacteria in a Brazilian Intensive Care Unit.

Pharmacodynamic analyses were proposed to determine optimal empirical antibiotic therapy against Gram-negative bacteria isolated in a Brazilian ICU. Due to high resistance rates, standard regimens of cefepime, ciprofloxacin, meropenem, and piperacillin/tazobactam were not able to attain significant bactericidal CFR. Prolonged infusion of meropenem achieved 88% CFR, making it a possible empirical regimen in this ICU until susceptibilities become available. Still, even through administration of high dose prolonged infusions, 12.0% of simulated subjects did not achieve bactericidal exposure, suggesting that combination therapy would frequently be required in this setting. In conclusion, we recommend that in the presence of identified resistance problems among Gram-negative bacteria in a unit or hospital, MIC testing of formulary agents should be conducted along with pharmacodynamic simulation to assist in choosing an optimal antibiotic and dosage regimen for empirical use of severe infections until cultures and susceptibilities become available.

A pharmacodynamic strategy to optimize empirical antibiotic therapy for gram-negative bacteria in a Brazilian Intensive Care Unit

Pharmacodynamic analyses were proposed to determine optimal empirical antibiotic therapy against Gram-negative bacteria isolated in a Brazilian ICU. Due to high resistance rates, standard regimens of cefepime, ciprofloxacin, meropenem, and piperacillin/tazobactam were not able to attain significant bactericidal CFR. Prolonged infusion of meropenem achieved 88 percent CFR, making it a possible empirical regimen in this ICU until susceptibilities become available. Still, even through administration of high dose prolonged infusions, 12.0 percent of simulated subjects did not achieve bactericidal exposure, suggesting that combination therapy would frequently be required in this setting. In conclusion, we recommend that in the presence of identified resistance problems among Gram-negative bacteria in a unit or hospital, MIC testing of formulary agents should be conducted along with pharmacodynamic simulation to assist in choosing an optimal antibiotic and dosage regimen for empirical use of severe infections until cultures and susceptibilities become available.

Antibiotic resistance and trend of urinary pathogens in general outpatients from a major urban city.

OBJECTIVE: We assessed the antimicrobial resistance patterns of pathogens responsible for urinary tract infections (UTI) in outpatients in São Paulo, Brazil, as well as the Escherichia coli antimicrobial resistance trend. MATERIALS AND METHODS: Outpatients urine cultures were collected from January 2000 to December 2003. Statistical analysis considered positive results for one bacterial species with colony count >or= 100,000 CFU/mL. Stratification was done on age group and gender. Statistical tests used included chi-square and the chi-square test for trend to evaluate differences between susceptibility rates among age groups and ordering in the E. coli resistance rates per year, respectively. RESULTS: There were 37,261 positive results with Enterobacteriaceae isolated in 32,530 (87.3%) and Gram-positive cocci in 2,570 (6.9%) cultures. E. coli had the highest prevalence (71.6%). Susceptibility tests were performed in 31,716 cultures. E. coli had elevated resistance rates (> 30%) to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Significant differences between age groups and ordering among years were observed. CONCLUSIONS: The use of trimethoprim-sulfamethoxazole is precluded in the population studied due to elevated resistance rates (> 30%) among most prevalent pathogens. Significant resistance rate differences among age groups and years were observed, particularly for fluoroquinolones. Fluoroquinolones should be used with caution. Nitrofurantoin should be used as empirical therapy for primary, non-complicated urinary tract infections.

Antibiotic resistance and trend of urinary pathogens in general outpatients from a major urban city

OBJECTIVE: We assessed the antimicrobial resistance patterns of pathogens responsible for urinary tract infections (UTI) in outpatients in São Paulo, Brazil, as well as the Escherichia coli antimicrobial resistance trend. MATERIALS AND METHODS: Outpatients urine cultures were collected from January 2000 to December 2003. Statistical analysis considered positive results for one bacterial species with colony count > 100,000 CFU/mL. Stratification was done on age group and gender. Statistical tests used included chi-square and the chi-square test for trend to evaluate differences between susceptibility rates among age groups and ordering in the E. coli resistance rates per year, respectively. RESULTS: There were 37,261 positive results with Enterobacteriaceae isolated in 32,530 (87.3 percent) and Gram-positive cocci in 2,570 (6.9 percent) cultures. E. coli had the highest prevalence (71.6 percent). Susceptibility tests were performed in 31,716 cultures. E. coli had elevated resistance rates (> 30 percent) to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Significant differences between age groups and ordering among years were observed. CONCLUSIONS: The use of trimethoprim-sulfamethoxazole is precluded in the population studied due to elevated resistance rates (> 30 percent) among most prevalent pathogens. Significant resistance rate differences among age groups and years were observed, particularly for fluoroquinolones. Fluoroquinolones should be used with caution. Nitrofurantoin should be used as empirical therapy for primary, non-complicated urinary tract infections.

In vitro synergy test of meropenem and sulbactam against clinical isolates of Acinetobacter baumannii.

Meropenem and imipenem are often the drugs of choice for the treatment of infections due to multidrug-resistant Acinetobacter baumannii. The present study aimed at evaluating the interaction between meropenem and sulbactam through microdilution and checkerboard methods against 48 clinical isolates of A. baumannii collected from Brazilian hospitals. All the isolates presented elevated minimum inhibitory concentration (>or=2 microg/mL) to either meropenem or sulbactam. The checkerboard method with the combination of meropenem and sulbactam demonstrated 29.2% (14/48) synergism, 47.9% (23/48) partial synergism, 10.5% (5/48) additive, 6.2% (3/48) indifference, and 6.2% (3/48) antagonism (SigmaFIC(min)=0.09 and SigmaFIC(max)=8). Thus, combinations of meropenem and sulbactam may show synergism or partial synergism for most A. baumannii isolates. Further studies may help identify treatment options for patients with infections caused by these organisms, particularly with this combination, where both drugs have time-dependent activities and might be suitable for therapy optimization studies.

Evaluation of the antimicrobial activity of sparfloxacin, relative to other oral antibiotics against 1,125 bacterial isolates from 10 medical centers in Brazil

A multicenter study was carried out in order to compare the in vitro activity of sparfloxacin, to ciprofloxacin, amoxicillin/clavulanic acid, cephalexin, cefuroxine and azithromycin, against 1,125 microorganisms recently isolated from clinical specimens, most of them representative of respiratory tract infections. Sparfloxacin demonstrated potent action and was more active than the ß-lactan agents and azithromycin against most of the bacterial strains tested. Sparfloxacin was more potent (96 percent and 95 percent sensitivity, with MIC90 of 0.19µg/mL and 0.5µg/mL, respectively) than the order antimicrobial agents tested against the Enterobacteriaceae family (Escherichia coli and Klebsiella pneumoniae). It was found to be equivalent in activity to ciprofloxacin (96 percent and 91 percent sensitivity and MIC90 of o.25 and 0.75µg/mL, respectively). Sparfloxacin was also found to be very active against the most fastidious microorganisms commonly associated to respiratory tract infections such as the penicillin-susceptible and resistant Haemophilus influenzae (MIC90 0.032µg/mL) and non ß-lactamase producing Moraxella catarrhalis (MIC90 0.5µg/mL).

Central venous catheter-related infections in intensive care units

Objective: To determine the rates of colonization and infection related to central venous catheter (CVC), the causative microorganisms, and the influence of various factors. Methods: From June to August 1993, all CVC in 4 Intensive Care Units were evaluated from their insertion to removal. Data were collected, by 3 nurses. Blood and catheter tips were cultured. Results: Of 84 catheters, 29.8 percent were colonized, 9.5 percent of patients showed evidence of local infection, and 4.8 percent had primary bloodstream infections. The internal jugular vein was the most commun site for catheter insertion (81 percent). Causes of removal were: end of need (48.3 percent), suspected infection (23.3 percent), malfunction (20 percent), routine change (8.3 percent). Among removals because of suspected infection 50 percent presented evidence of local infection, 43 percent were colonized (>15cfu), but there were no bloodstream infections. The average time of catheter use for those which became colonized was longer than for catheters that did not become colonized (p=0.008). The average time of catheter use associated with removal for infection (local and bloodstream) was longer than for removal for other reasons (p=0.042). Among colonized catheters, 16 percents developed bloodstream infection and 20 percent local infection. Immunosupressive drugs, cancer, diabets mellitus, HIV-infection, and neutropenia were not associated with infection or colonization. The most common microorganisms were gram-negative rods and S.aureus. Conclusions: The duration of venous catheter use increased the risk of colonization and infection. The observation suggests that physicians must strive for the shortest time of use of venous catheters, but it does not indicate a need for routine central venous catheter removal.

Identificaçåo de bactérias gram positivas resistentes à vancomicina / Identification of vancomycin resistant gram positive bacteria

Infecçöes por bactérias Gram positivas resistentes à vancomicina têm surgido com aior frequência nos últimos anos, causando problemas clínicos e terapêuticos. Os laboratórios de microbiologia devem adequar-se técnicamente para detecçåo e identificaçåo destes microorganismos. Apresentamos uma revisåo bibliográfica sobre a importância clínica destes agentes bem como um fluxograma simplificado para sua correta identificaçåo