Outcome and Adequacy of Empirical Antibiotherapy in Post-Operative Peritonitis: A Retrospective Study.

Background: Empirical antibiotherapy (EA) should target all bacteria in post-operative peritonitis (PP). Nevertheless, recent studies failed to prove a link between adequacy of EA and prognosis of PP. We sought to confirm this loss of association between adequate EA and prognosis and to analyze the evolution of patients' characteristics and antimicrobial strategies. Methods: This is was retrospective study. Patients with a positive fungal culture were excluded. The cohort was divided into two time periods. Data of survivors and non-survivors were compared within each time period. Differences between the two periods were assessed. A multivariable analysis searched for parameters associated with a higher hospital mortality rate. Results: Two hundred fifty-one patients were included, with 92 patients in the first period (P1) and 152 patients in the second period (P2). Inadequate EA was associated with a worse outcome only in P1. The multivariable analysis in the whole cohort showed that inadequate EA was associated with a higher mortality rate. When the differences noticed between the two periods were entered in the model (presence of resistant gram-positive cocci and EA comprising glycopeptides), inadequate EA was no longer associated with worse outcome. In P1, the most severe patients had more resistant bacteria, hence, had a higher rate of inadequate EA. This artifact disappeared in P2, during which broader antibiotherapies with triple EA were more often prescribed for the most severe patients. Conclusion: This study showed that the link between inadequate EA and outcome of patients with PP was at least partly artifactual in older studies.

Pseudomonas aeruginosa eradication therapy and risk of acquiring Aspergillus in young children with cystic fibrosis.

BACKGROUND: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown. AIM: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years. METHODS: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years. RESULTS: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event. CONCLUSION: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. cephalosporins and penicillins.

Acute pulmonary exacerbations (APE) are well-described complications of cystic fibrosis (CF) and are associated with progressive morbidity and mortality. Despite aggressive management with two or more intravenous anti-pseudomonal agents, approximately 25% of exacerbations will result in a loss of lung function. The aim of this review is to provide an evidence-based summary of pharmacokinetic/pharmacodynamic (PK/PD), tolerability, and efficacy studies utilizing anti-pseudomonal cephalosporins (i.e., ceftazidime and cefepime) and penicillins (i.e., piperacillin-tazobactam and ticarcillin-clavulanate) in the treatment of APE and to identify areas where further study is warranted. The ceftazidime and cefepime dosing ranges from the literature are 200-400 mg/kg/day divided every 6-8 hr, maximum 8-12 g/day, and 150-200 mg/kg/day divided every 6-8 hr, up to 6-8 g/day, respectively. The literature supported dosing ranges for piperacillin and ticarcillin are 350-600 mg/kg/day divided every 4 hr, maximum 18-24 g/day of piperacillin component, and 400-750 mg/kg/day divided every 6 hr, up to 24-30 g/day of ticarcillin component, respectively. As a large portion of CF patients will not regain their lung function following an APE, we suggest the need to optimize antibiotic dosing and dosing regimens used to treat an APE in efforts to improve outcomes for CF patients infected with Pseudomonas aeruginosa. Future studies are needed to determine the clinical efficacy of higher than FDA-approved doses of ceftazidime, cefepime, and ticarcillin-clavulanate in APE. The usefulness of high dose piperacillin (>600 mg/kg/day) may be limited due to treatment-related adverse effects. Further understanding of these adverse effects in CF patients is needed.

Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections.

Topical compounded Timentin(®) diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin(®) (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt(®) against P. aeruginosa and to determine the efficacy and stability of Timentin(®) aqueous stock concentrate solution. Timentin(®) stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or -20°C. The diluted Timentin(®)-Methopt(®) solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4°C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at -20°C and was also acceptable for shorter time periods (6-9 months) when stored at 4°C. The MIC for the diluted Timentin(®)-Methopt(®) solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24°C. The results of this study indicate that storage of the Timentin(®) stock solution at -20°C does not compromise efficacy for at least 12 months and that Timentin(®) diluted in Methopt(®) was stable for 28 days when stored at either 4 or 24°C.

The costs of treatment of early and chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

[Hepatic inflammatory pseudotumor regressing with antibiotic therapy]. / Pseudo-tumeur inflammatoire hépatique régressant sous antibiothérapie.

INTRODUCTION: Inflammatory hepatic pseudo-tumors are rare, non-neoplastic lesions, and their diagnosis is usually made on hepatectomy samples. OBSERVATION: The general health of a 77 year-old patient was suddenly altered and clinical examination (and scan) revealed a hepatic tumor. Diagnosis of inflammatory hepatic pseudo-tumor was evoked by analysis of a biopsy. In view of the age and the general state of the patient we chose prolonged antibiotic therapy rather than hepatic surgery. Nine months later, the tumor had regressed. COMMENTS: Because they are rare (100 cases described), hepatic pseudo-tumors raise two questions: can diagnosis be made simply by biopsy or should one always analyze the complete sample and, if hepatectomy is contraindicated, is non-surgical treatment effective? The progression of our patient permits us to reply positively to both questions.

Once-daily, high-dose levofloxacin versus ticarcillin-clavulanate alone or followed by amoxicillin-clavulanate for complicated skin and skin-structure infections: a randomized, open-label trial.

This study tested whether levofloxacin, at a new high dose of 750 mg, was effective for the treatment of complicated skin and skin-structure infections (SSSIs). Patients with complicated SSSIs (n=399) were randomly assigned in a ratio of 1:1 to 2 treatment arms: levofloxacin (750 mg given once per day intravenously [iv], orally, or iv/orally) or ticarcillin-clavulanate (TC; 3.1 g given iv every 4-6 hours) followed, at the investigator's discretion, by amoxicillin-clavulanate (AC; 875 mg given orally every 12 hours). In the clinically evaluable population, therapeutic equivalence was demonstrated between the levofloxacin and TC/AC regimens (success rates of 84.1% and 80.3%, respectively). In the microbiologically evaluable population, the overall rate of eradication was 83.7% in the levofloxacin treatment group and 71.4% in the TC/AC treatment group (95% confidence interval, -24.3 to -0.2). Both levofloxacin and TC/AC were well tolerated. These data demonstrate that levofloxacin (750 mg once per day) is safe and at least as effective as TC/AC for complicated SSSIs.

Eficacia clínica de roxitromicina frente a amoxicilina/clavulánico en la profilaxis antimicrobiana tras cirugía de cordal incluido

Objetivo: Estudiar la eficacia y seguridad de roxitromicina 300 mg en una toma diaria y la asociación amoxicilina/clavulánico 500/125 mg cada 8 horas, en la profilaxis antimicrobiana de la cirugía de cordal incluido. Confirmar los datos de actividad anti-inflamatoria de roxitromicina publicados por otros autores. Diseño del estudio: Estudio ramdomizado, comparativo, prospectivo, no controlado, de fase IV. La eficacia clínica de ambos fármacos se valoró de acuerdo a la puntuación obtenida en la escala de "Criterios de Evaluación de Eficacia para Antibióticos" de la Sociedad Japonesa de Cirugía Oral; rango: 2 (más eficaz)-21 (menos eficaz) Resultados: Todos los pacientes reclutados (74) completaron el estudio. La puntuación total al final del estudio fue inferior en los pacientes que recibieron roxitromicina (2,9 ñ 1,5) frente a los tratados con amoxicilina/clavulánico (3,9 ñ 2,5) [p=0,l4]. También fueron mejores para roxitromicina el cociente entre la puntuación después y antes del tratamiento (0,41 ñ 0,21 frente a 0,53 ñ 0,39 [p=0,72]) y el porcentaje de pacientes que consideraron el tratamiento con el fármaco como excelente o eficaz (88,1 por ciento vs 70,9 por ciento; [p= 0,07]). El consumo de anti-inflamatorios fue similar en ambos grupos de tratamiento (7,4 ñ4,1 comprimidos semanales en el grupo roxitromicina vs. 8,0 ñ 4,1 comprimidos semanales en el grupo amoxicilina/clavulánico [p= 0,47]). En el grupo amoxicilina/clavulánico 29/32 pacientes comunicaron algún tipo de efecto adverso (90,6 por ciento) por tan sólo 12/42 pacientes en el grupo roxitromicina (29 por ciento) [p<0.0001]). Discusión: Roxitromicina a dosis de 300 mg/día y amoxicilina/clavulánico a dosis de 500/125 mg cada 8 horas son dos regímenes profilácticos igualmente efectivos en la prevención de las complicaciones infecciosas tras la cirugía de cordal incluido. Roxitromicina presenta un perfil de tolerabilidad y cumplimentación, significativamente superiores a las de amoxicilina/clavulánico, lo que la sitúa como un antibiótico de primera elección en la profilaxis antimicrobiana que acompaña estos procedimientos (AU)

Estudio de la idoneidad de la prescripción antibiótica en el Hospital Monte Naranco. Oviedo / Study of the appropiateness of antibiotic prescription in the Hospital Monte Naranco

Objetivos: 1. Describir la frecuencia y distribución de uso de antibióticos en el hospital para los distintos procesos tal como se diagnostican en la historia clínica. 2, Evaluar la adecuación del uso a los criterios diagnósticos y terapéuticos. Material y métodos: Se trata de un estudio observacional y trasversal a partir de una muestra aleatoria de las altas hospitalarias desde el 01/01/99 al 31/09/99. El universo poblacional fueron las altas cerradas y codificadas y la información se obtuvo de la historia clínica mediante un cuestionario diseñado a tal efecto que recoge variables de filiación, diagnóstico principal y otros diagnósticos, criterios que justifican la indicación del antibiótico, indicadores de proceso, cambio de antibiótico y motivo, indicadores de evolución de la enfermedad y clinica que justifica el diagnóstico, obteniéndose una muestra de 411 historias clínicas. La información fue recogida y revisada por los autores. Los criterios de infección y de indicación de tratamiento proceden de los establecidos por los Centers for Disease Control y las recomendaciones de diferentes sociedades científicas. Resultados: En el 25 por ciento de las historias clínicas revisadas contaba indicación de tratamiento antibiótico. Prescritos en el centro fueron el 49 por ciento de los tratamientos, de los cuales el 30 por ciento corresponden a cambios de tratamiento, mientras que el 51 por ciento de los tratamientos fueron inducidos por el centro de referencia. El 88 por ciento de las indicaciones de los tratamientos antibióticos del centro y 76 por ciento del total fueron amoxicilina-ácido clavulánico u ofloxacino. La adecuación de los diagnósticos a los criterios, varió según diagnóstico, entre el 44 por ciento para infección cutánea, con una media de 54 por ciento. La adecuación de los diagnósticos a los criterios, varió según diagnóstico, entre el 44 por ciento para infección de las vías respiratorias bajas y el 61 por ciento, para infección cutánez, con una media de 54 por ciento. La adecuación de la prescripción respecto al diagnóstico que figuraba en la historia clínica y su duración varió entre el 91,5 por ciento para infección respiratoria y 100 por ciento para neumonías. La duración media de tratamiento fue de 9,6 días, con escasa variabilidad dentro de los tratamientos y entre infecciones, y sólo el 14 por ciento de los tratamientos fue correcta para las infecciones urinarias. La vía intravenosa se mantuvo, en la media, durante el 80 por ciento del tiempo del tratamiento. Conclusiones: En este estudio se observa un uso correcto de antibióticos en relación con el diagnóstico que figura en la historia clínica. Sin embargo sólo en la mitad de los casos se cumplen los criterios diagnósticos y la duración del tratamiento de infecciones urinarias así como el tratamiento intravenoso parecen largos. Las consecuencias de esto pueden ser iatrogenia y gastos innecesarios. Por tanto, los aspectos mejorables en la utilización de antibióticos en el Hospital Monte Naranco son fundamentalmente el cumplimiento de criterios diagnósticos y la duración de los tratamientos. Se recomienda como estrategia para mejorar la calidad de prescripción de antibióticos un acercamiento multidisciplinar que incluya: 1. consenso en el uso, 2. programas de formación 3. audits médicos, 4. revisión de los criterios diagnósticos y las indicaciones terapéuticas adaptados a la población usuaria de este centro (AU)

Comparative effectiveness and safety of cefdinir and amoxicillin-clavulanate in treatment of acute community-acquired bacterial sinusitis. Cefdinir Sinusitis Study Group.

Cefdinir is an extended-spectrum oral cephalosporin that is active against pathogens commonly seen in acute community-acquired bacterial sinusitis (ACABS), including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Two randomized, investigator-blind, multicenter trials (one in the United States and one in Europe) compared two dosage regimens of cefdinir (600 mg once a day for 10 days and 300 mg twice a day for 10 days) to amoxicillin-clavulanate (A-C) (500 mg three times a day for 10 days) for adult and adolescent patients with ACABS. Twelve hundred twenty-nine patients entered the U.S. study, 698 with antral puncture; 569 patients entered the European study, all with antral puncture. Clinical response (cure or improvement) was determined 7 to 14 days and 3 to 5 weeks posttherapy. Microbiologic eradication rates were determined 10 to 30 days posttherapy in a subset of patients who underwent pre- and posttherapy sinus aspirate culture. Rates of adverse events and treatment discontinuations due to adverse events were examined. Cefdinir, given once or twice daily, was as effective clinically (approximately 90% cure rate) as amoxicillin-clavulanate given three times daily in the treatment of ACABS. Microbiologic eradication rates were also similar in the three groups. The major side effect was mild diarrhea, occurring in approximately 20% of each group. Cefdinir caused fewer adverse events requiring treatment discontinuation.

Comparison of ceftibuten versus amoxicillin/clavulanate in the treatment of acute exacerbations of chronic bronchitis.

The efficacy and tolerability of once- or twice-daily ceftibuten (400 mg daily) were compared with three-times daily amoxicillin/clavulanate (AMX/CA, 500 mg/125 mg) in the treatment of acute exacerbations of chronic bronchitis (AECB) in an open, parallel-group 10- to 14-day study in 443 patients. Patients were assessed at baseline and on days 5, 10-14 and after 4-6 weeks of treatment, and the clinical response defined as cured, improved, stabilized or failed. Clinical efficacy between the 3 groups was equivalent (p = 0.002) with 90% of patients in each group responding to treatment (cured or improved) and the incidence of complete cures (with no clinical signs of relapse) was also equivalent. In conclusion, this study showed that ceftibuten is clinically equivalent to a standard regimen of amoxicillin/clavulanate in the treatment of AECB, including those patients infected with Streptococcus pneumonia. Ceftibuten was better tolerated than AMX/CA and was associated with significantly fewer gastrointestinal side effects. Furthermore, once-daily was a well tolerated and effective as twice-daily ceftibuten.

Endocarditis caused by Stenotrophomonas maltophilia: case report and review.

Stenotrophomonas (Xanthomonas) maltophilia is a rare cause of endocarditis. The extensive resistance of this organism to several antibiotics leaves few options for antimicrobial therapy. In vitro synergism of the combination of trimethoprim-sulfamethoxazole (TMP-SMZ) and ticarcillin/clavulanic acid (TIC/CA) has been demonstrated. To our knowledge, we report the first case of ventriculoatrial cerebrospinal fluid shunt-associated endocarditis due to S. maltophilia. The patient was cured with combination therapy with TMP-SMZ and TIC/CA along with catheter removal. This is also the first report of S. maltophilia endocarditis successfully treated with this antibiotic combination. In a review of the medical literature, only 16 cases of S. maltophilia endocarditis were found. Most patients were intravenous drug users (43.8%) or had either prosthetic heart valves (50%) or an indwelling vascular catheter (18.8%). Although S. maltophilia is usually considered a nosocomial pathogen, about one-half of the cases were community-acquired. Twelve of sixteen patients had left-sided endocarditis. Therapy with a combination of two or more antibiotics was employed in most cases. Seven patients had been given TMP-SMZ therapy, but none had been treated with TIC/CA before. One-half of the patients required cardiac surgery. The overall mortality rate was 33%. Although the optimal antibiotic treatment for S. maltophilia endocarditis remains unknown, the case reported herein reinforces in vitro findings that the combination of TMP-SMZ and TIC/CA may be effective therapy.

Mediastinitis related to probable central vinblastine extravasation in a woman undergoing adjuvant chemotherapy for early breast cancer.

Adjuvant chemotherapy for breast cancer, although generally safe and of proven benefit, can have severe complications. Central venous catheter (CVC) complications are relatively common forms of treatment-related morbidity in this setting. We report a rare type of CVC-related complication, that of chemotherapy-induced mediastinitis from central venous extravasation of the drug vinblastine, in a women undergoing adjuvant chemotherapy. The patient presented with signs and symptoms consistent with mediastinitis, but the diagnosis was delayed because the initial findings were nonspecific and there was little suspicion for a CVC-related problem. A radionuclide venous flow study was misleading, but a computed tomographic study of the chest and contrast venography confirmed the diagnosis. Conservative treatment with CVC removal, systemic anticoagulation, antibiotics, and pain controlled to gradual improvement in the patient's clinical status. More aggressive strategies, such as thrombolytic therapy and surgical intervention, were considered, but these approaches have not been used in this particular setting. The complication reported here is the first described in the literature in an adult patient. Two similar cases have been reported in pediatric patients. It is likely that this clinical problem is underreported. Patients with CVCs actively undergoing chemotherapy with vesicant agents should be watched carefully for early signs of CVC disruption and subsequent extravasation, as it is likely that early intervention will be of benefit.

Stenotrophomonas maltophilia: emergence of multidrug-resistant strains during therapy and in an in vitro pharmacodynamic chamber model.

Emergence of Stenotrophomonas maltophilia as a nosocomial pathogen is becoming increasingly apparent. Pleiotropic resistance characterizes S. maltophilia. Furthermore, a slow growth rate and an increased mutation rate generate discordance between in vitro susceptibility testing and clinical outcome. Despite original susceptibility, drug-resistant strains of S. maltophilia are often recovered from patients receiving beta-lactams, quinolones, or aminoglycosides. Given the disparity among various in vitro susceptibility methods, this study incorporated a unique pharmacodynamic model to more accurately characterize the bacterial time-kill curves and mutation rates of four clinical isolates of S. maltophilia following exposure to simulated multidose regimens of ceftazidime, ciprofloxacin, gentamicin, and ticarcillin-clavulanate. Time-kill data demonstrated regrowth of S. maltophilia with all four agents. With the exception of ticarcillin-clavulanate, viable bacterial counts at the end of 24 h exceeded the starting inoculum. Ciprofloxacin only reduced bacterial counts by less than 1.0 log prior to rapid bacterial regrowth. Resistant mutant strains, identical to their parent strain by pulsed-field gel electrophoresis, were observed following exposure to each class of antibiotic. Mutant strains also had distinct susceptibility patterns. These data are consistent with previous reports which suggest that S. maltophilia, despite susceptibility data that imply that the organism is sensitive, develops multiple forms of resistance quickly and against several classes of antimicrobial agents. Standard in vitro susceptibility methods are not completely reliable for detecting resistant S. maltophilia strains; and therefore, interpretation of these results should be done with caution. In vivo studies are needed to determine optimal therapy against S. maltophilia infections.

Correlation of in-vitro activity and pharmacokinetic parameters with in-vivo effect of amoxycillin, co-amoxiclav and cefotaxime in a murine model of pneumococcal pneumonia.

In an attempt to determine the susceptibility breakpoints for amoxycillin, co-amoxiclav and cefotaxime in pneumococcal pneumonia, a neutropenic mouse model was established and tested with two strains having different susceptibility to penicillins and cefotaxime. With a penicillin-sensitive strain (MIC/MBC = 0.01/0.01 mg/L) the minimum dosage tested achieving significant cure was 2 mg/kg for amoxycillin, co-amoxiclav and cefotaxime. For the penicillin-insensitive strain (MIC/MBC = 1/2 mg/L), the minimum dosage tested giving significant cure was 50 mg/kg for amoxycillin and co-amoxiclav but 100 mg/kg for cefotaxime. Our results support the belief that MICs of amoxycillin, co-amoxiclav and cefotaxime for pneumococcal strains of < or = 0.5 or < or = 1 mg/L can be considered as clinically relevant susceptibility breakpoints.

Sparfloxacin for the treatment of community-acquired pneumonia: a pooled data analysis of two studies.

A pooled data analysis of two double-blind studies encompassing 1137 episodes of community-acquired pneumonia in hospitalised adults, of which 560 were treated with sparfloxacin and 577 were randomised to comparator antibacterial agents (amoxycillin/clavulanic acid, erythromycin or amoxycillin administered at reference dosages), was performed. The global efficacy rate at the end of treatment in evaluable patients treated with sparfloxacin was 88.3% compared with 84.1% in those who received comparator antibacterial agents. This analysis verified the efficacy of this new aminofluoroquinolone, given orally once daily, in the treatment of community acquired pneumonia. The overall outcome favoured sparfloxacin for use in the empirical treatment of community-acquired pneumonia.

Antibiotic treatment for uncomplicated neuropathic forefoot ulcers in diabetes: a controlled trial.

To investigate the effect of oral antibiotics in purely neuropathic ulcers (Wagner grade 1-2, no osteomyelitis), a double blind placebo-controlled study was performed. Forty-four patients were enrolled and subjected to standard treatment with absolute pressure relief (half shoes), daily wound cleansing (topical disinfectant), sterile dressings (specialized nurse). Patients were randomized to an antibiotic (amoxicillin plus clavulanic acid), or placebo. The study was stopped when the antibiotic proved unsuitable according to swab result, or on clinical grounds (no improvement within 6 days of recruitment). Main outcome measure was the ulcer closing rate during 20 days, as assessed by standardized photographs. All ulcers except one were infected. Of the placebo group (n = 22), 2 patients had to be withdrawn within 6 days, versus 3 patients of the antibiotic-group (n = 22). In the placebo group, 10 ulcers were healed versus 6 ulcers in the antibiotic group (NS). Mean (95% CI) reduction in ulcer radius was 0.41 (0.21-0.61) mm day-1 in the placebo group versus 0.27 (0.15-0.39) mm day-1 in the antibiotic group (NS). In conclusion, there is no benefit from antibiotic treatment with amoxicillin plus clavulanic acid as a supplement to standard therapy in uncomplicated neuropathic foot ulcers, provided pressure relief is complete, and wound care is performed strictly supervised. However, a Type-II statistical error cannot be excluded in this small study.

Methicillin-resistant coagulase-negative staphylococcal osteomyelitis and its relationship to broad-spectrum oral antibiosis in a predominantly diabetic population.

Awareness of the virulence of coagulase-negative Staphylococci, previously regarded as saprophytes with minimal pathogenicity, has steadily increased. Eighty-seven individual patients diagnosed with acute osteomyelitis, as confirmed by microbiologic and pathologic analysis, were included in this study. Of these patients, 82% (71/87) were known to have diabetes mellitus. The prevalence of coagulase negative Staphylococcus was 40% (35/87) in deep bone cultures, 63% (22/35) of which were methicillin resistant. When the coagulase negative Staphylococcus group was assessed for prior long-term (> 2 week) oral antibiotic treatment with ciprofloxacin, it was found that 54% (12/22) of the methicillin-resistant coagulase-negative Staphylococcal infected patients had received such treatment, compared with 15% (2/13) of patients with methicillin-sensitive coagulase-negative Staphylococcal osteomyelitis (p < 0.034). When the group was analyzed for prior long-term antibiotic treatment with amoxicillin/clavulanate, 23% (5/22) of the methicillin-resistant patients had received oral amoxicillin/clavulanate, compared with 23% (3/13) of patients with methicillin-sensitive coagulase-negative Staphylococcal osteomyelitis (p > 0.05). Prevalence of polymicrobial infections, which constituted 29% (25/87) of all individual patients, was also analyzed. Of those patients with coagulase-negative isolates, 29% (10/35) were polymicrobial (p > 0.05). The results from this study suggest that infections of bone caused by coagulase-negative Staphylococci are associated with a high prevalence of methicillin resistance. This study also raises the question of whether injudicious prolonged use of ciprofloxacin may, in fact, promote proliferation of resistant organism strains.

Comparative evaluation of the clinical and microbiological efficacy of co-amoxiclav vs cefixime or ciprofloxacin in bacterial exacerbation of chronic bronchitis.

In an open randomized study 218 outpatients (159 males and 59 females) ranging between 18 and 85 years of age (mean 61.9) suffering from bacterial exacerbation of chronic bronchitis have been randomly treated: 79 with co-amoxiclav (amoxicillin 875 mg+clavulanic acid 125 mg) twice daily, 69 with cefixime (400 mg) once daily, and 70 with ciprofloxacin (500 mg) twice daily for an average period of 10 days. Before treatment start, 234 bacterial strains (105 Gram-positive and 129 Gram-negative) were isolated as the cause of exacerbation; the leading pathogens were Streptococcus pneumoniae and Haemophilus spp. Eradication rates at the end of treatment were 82.2% for the co-amoxiclav group, 77.6% for the cefixime group, and 81.2% for ciprofloxacin group. Clinical success (cure+improvement) was obtained in 90.8% of the cases treated with co-amoxiclav, in 80.9% for the cefixime group and in 85.7% of patients treated with ciprofloxacin. Seven adverse events (8.9%) of which 4 cases of diarrhea and 3 of itching, were recorded in the co-amoxiclav group. Eleven adverse events (14.7%) were recorded in the cefixime group including gastrointestinal disturbances in 6 patients and mild to moderate increase of liver function in 2. Nine adverse events (12.9%) occurred in the ciprofloxacin group, including insomnia in 3 patients, gastrointestinal disturbances in 2, and serious increase of liver function tests in one patient. It can be concluded that there were no statistically significant differences among the three treatment groups. However, co-amoxiclav demonstrated a higher efficacy rate than cefixime and ciprofloxacin and was better tolerated. Therefore, it can be used as a first-choice drug in the treatment of exacerbation of chronic bronchitis.