Protection Against Chronic Pyelonephritis in Rats by Suppression of Acute Suppuration: Effect of Colchicine and Neutropenia

Previous experiments in rats have suggested that renal scarring after acute, obstructive pyelonephritis due to Escherichia coli results from parenchymal damage due to acute inflammation and suppuration. To assess the role of acute infiltration by polymorphonuclear leukocytes (PMNLs) in the pathogenesis of chronic pyelonephritis (CPN), rats were either treated with colchicine to depress leukcoyte motility or rendered neutropenic with a single dose of cyclophosphamide. Colchicine given during acute pyelonephritis reduced kidney inflammation and protected against CPN two months later. Similarly, neutropenia reduced acute inflammation and protected against chronic parenchymal destruction and scarring. Protection against renal scarring in both colchicine-treated and neutropenic rats occurred despite higher renal bacterial counts during acute pyelonephritis. These experiments provide further evidence that CPN (renal scarring) results from kidney damage that occurs during early acute obstructive pyelonephritis. This damage appears to result from infiltration of the kidney by PMNLs rather than direct damage from bacterial infectio

In-vitro activity of temafloxacin for Gram-positive pathogens

The antimicrobial activity of tcmafioxacin against aerobic Gram-positive cocci was compared to that of ciprofloxacin, ofloxacin, fleroxacin and pefloxacin using the broth microdilution technique. Temafloxacin was mom active than the other four fluoroquinolones, particularly for viridans streptococci and Streptococcus pneumoniaeniae. The MIC90 of temafloxacin was at least four-fold lower than that of ciprofloxacin and ofloxacin for viridans strtptococci and penicillin-susceptible pneumococci. The MIC50s and MIC90s of temafloxacin were equal to or lower than those of the other fluoroquinolones for rnethicillin-susceptible Staphylococnu aureus (MSSA), methicillin-resistant S.aureus (MRSA), and methicillin-susceptible and methicillin-resistant coagulasc-negative staphylococci Temafloxadn was more active against all the other Gram-positive aerobes (except Enterococcus faecalis) tested than the other fluorquinolone

An Epidemic of Food-Borne Listeriosis in Western Switzerland: Description of 57 Cases Involving Adults

This article describes 57 cases of listeriosis that occurred in adults in western Switzerland during an outbreak associated with the consumption of a soft cheese. Twenty-one percent of the cases were of bacteremia, 40% were of meningitis, and 39% were of meningoencephalitis. Overall, 42% of the patients had an underlying disease and 54% were >65 years of age. Patients with bacteremia were significantly older than those with meningitis or meningoencephalitis (median ages, 75, 69, and 55 years, respectively). The epidemic strain, defined by phage typing, was isolated in three-quarters of the listerial cases observed during the epidemic period and did not appear to differ significantly from the nonepidemic strains in terms of virulence. The overall mortality associated with the 57 cases was 32%. Among the patients' characteristics, age and type of clinical presentation were independent predictors of death in a multivariate logistic regression model (pseudo-r2 [coefficient of determination], .26; both P values <.05), and a presentation of meningoencephalitis was associated with an increased death risk (odds ratio, 6.5; 95% confidence interval, 1.1-39.5; P < .05). Neurological sequelae developed in 30% of the survivors of CNS listeriosi

β-Lactam Resistance Mechanisms of Methicillin-Resistant Staphylococcus aureus

In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from ⩾64 to 8 µg/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (⩾64 µg/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a ⩾90% successful amoxicillin treatment of experimental endocarditis due to penicillinasenegative MRSA compared with cloxacillin, which was totally ineffective (P < .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive β-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infection

New Diagnostic Real-Time PCR for Specific Detection of Mycoplasma hominis DNA

Mycoplasma hominis is a fastidious micro-organism causing genital and extragenital infections. We developed a specific real-time PCR that exhibits high sensitivity and low intrarun and interrun variabilities. When applied to clinical samples, this quantitative PCR allowed to confirm the role of M. hominis in three patients with severe extragenital infections

Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes

Background. Voriconazole is the therapy of choice for aspergillosis and a new treatment option for candidiasis. Liver disease, age, genetic polymorphism of the cytochrome CYP2C19, and comedications influence voriconazole metabolism. Large variations in voriconazole pharmacokinetics may be associated with decreased efficacy or with toxicity. Methods. This study was conducted to assess the utility of measuring voriconazole blood levels with individualized dose adjustments. Results. A total of 181 measurements with high-pressure liquid chromatography were performed during 2388 treatment days in 52 patients. A large variability in voriconazole trough blood levels was observed, ranging from ⩽1 mg/L (the minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) in 25% of cases to >5.5 mg/L (a level possibly associated with toxicity) in 31% of cases. Lack of response to therapy was more frequent in patients with voriconazole levels ⩽1 mg/L (6 [46%] of 13 patients, including 5 patients with aspergillosis, 4 of whom were treated orally with a median dosage of 6 mg/kg per day) than in those with voriconazole levels >1 mg/L (15 [12%] of 39 patients; P=.02). Blood levels >1 mg/L were reached after increasing the voriconazole dosage, with complete resolution of infection in all 6 cases. Among 16 patients with voriconazole trough blood levels >5.5 mg/L, 5 patients (31%) presented with an encephalopathy, including 4 patients who were treated intravenously with a median voriconazole dosage of 8 mg/kg per day, whereas none of the patients with levels ⩽5.5 mg/L presented with neurological toxicity (P=.002). Comedication with omeprazole possibly contributed to voriconazole accumulation in 4 patients. In all cases, discontinuation of therapy resulted in prompt and complete neurological recovery. Conclusions. Voriconazole therapeutic drug monitoring improves the efficacy and safety of therapy in severely ill patients with invasive mycose

Percentage, Bacterial Etiology and Antibiotic Susceptibility of Acute Respiratory Infection and Pneumonia among Children in Rural Senegal

Acute respiratory infections (ARI) are still a major health problem in most developing countries. So far no study has evaluated the importance of childhood ARI in rural Senegal. We prospectively studied ARI, the percentage of pneumonia and related mortality, as well as the bacterial composition of nasopharyngeal flora using nasopharyngeal aspirates in 114 children, aged 2-59 months, presenting at Ndioum's pediatric ward. Excluded from the trial were those children that had had antimicrobial therapy in the previous 2 weeks. The Kirby-Bauer method was used to determine antibiotic resistance throughout the study. The percentage of ARI and pneumonia among the population tested was 24 per cent and 11 per cent respectively. Streptococcus pneumonia was often resistant to cotrimoxazole (31 per cent) but only 9 per cent were resistant to chloramphenicol and 14 per cent to penicillin. Haemophilus influenzae (HI) was uniformly sensitive to ampicillin, and only 4 per cent were resistant to chloramphenicol and 11 per cent to cotrimoxazole. We conclude that SP and HI resistance to cotrimoxazole is important and warrants larger clinical trials using chloramphenicol. Information campaigns and intense management of comorbidities are desirable in this type of population. Comorbidities (tuberculosis, malaria, HIV‐AIDS, severe malnutrition) are determinant variables in many ARI cases and carry a high negative prognosis valu

Quantitative Antibiogram as a Typing Method for the Prospective Epidemiological Surveillance and Control of MRSA Comparison with Molecular Typing

Abstract Objective: Evaluation of the quantitative antibiogram as an epidemiological tool for the prospective typing of methicillin-resistant Staphylococcus aureus (MRSA), and comparison with ribotyping. Methods: The method is based on the multivariate analysis of inhibition zone diameters of antibiotics in disk diffusion tests. Five antibiotics were used (erythromycin, clindamycin, cotrimoxazole, gentamicin, and ciprofloxacin). Ribotyping was performed using seven restriction enzymes (EcoRV, HindIII, KpnI, PstI, EcoRI, SfuI, and BamHI). Setting: 1,000-bed tertiary university medical center. Results: During a 1-year period, 31 patients were found to be infected or colonized with MRSA. Cluster analysis of antibiogram data showed nine distinct antibiotypes. Four antibiotypes were isolated from multiple patients (2, 4, 7, and 13, respectively). Five additional antibiotypes were isolated from the remaining five patients. When analyzed with respect to the epidemiological data, the method was found to be equivalent to ribotyping. Among 206 staff members who were screened, six were carriers of MRSA. Both typing methods identified concordant of MRSA types in staff members and in the patients under their care. Conclusions: The quantitative antibiogram was found to be equivalent to ribotyping as an epidemiological tool for typing of MRSA in our setting. Thus, this simple, rapid, and readily available method appears to be suitable for the prospective surveillance and control of MRSA for hospitals that do not have molecular typing facilities and in which MRSA isolates are not uniformly resistant or susceptible to the antibiotics teste