To assess whether methicillin resistance is a microbial characteristic associated with deleterious clinical outcome, we performed a cohort study on 908 consecutive episodes of Staphylococcus aureus bacteremia and a case-control study involving 163 pairs of patients matched for preexisting comorbidities, prognosis of the underlying disease, length of hospitalization, and age. Of 908 bacteremic episodes, 225 (24.8%) were due to methicillin-resistant S. aureus (MRSA). Multivariate analysis did not reveal that methicillin resistance was an independent predictor for mortality when shock, source of bacteremia, presence of an ultimately or rapidly fatal underlying disease, acquisition of the infection in an intensive care unit (ICU), inappropriate empirical therapy, female sex, and age were taken into account. Nonetheless, methicillin resistance was an independent predictor for shock. The case-control study could not confirm that shock was linked to MRSA when prior antimicrobial therapy, inappropriate treatment, ICU residence, and female sex were considered. Our data suggest that cohort studies tend to magnify the relationship of MRSA with clinical markers of microbial pathogenicity and that this effect is a shortcoming of these kind of studies that is caused by inadequate control for underlying diseases.

Differences in the presence of nine urovirulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men have been studied. Hemolysin and necrotizing factor type 1 occur significantly more frequently among isolates causing prostatitis than among those causing cystitis (P < 0.0001) or pyelonephritis (P < 0.005). Moreover, the papGIII gene occurred more frequently in E. coli isolates associated with prostatitis (27%) than in those associated with pyelonephritis (9%) (P < 0.05). Genes encoding aerobactin and PapC occurred significantly less frequently in isolates causing cystitis than in those causing prostatitis (P < 0.01 and P < 0.0001, respectively) and pyelonephritis (P < 0.01 and P < 0.0001, respectively). No differences in the presence of Sat or type 1 fimbriae were found. Finally, AAFII and Bfp fimbriae are no longer considered uropathogenic virulence factors since they were not found in any of the strains analyzed. Overall, the results showed that clinical isolates producing prostatitis need greater virulence than isolates producing pyelonephritis in women or, in particular, cystitis in women (P < 0.05). Overall, the results suggest that clinical isolates producing prostatitis are more virulent that those producing pyelonephritis or cystitis in women.Urinary tract infections (UTIs) are one of the most common infectious diseases encountered in the clinical practice, mainly being associated with different members of the family Enterobacteriaceae. In fact, Escherichia coli is by far the most predominant pathogen causing UTIs (4,18,19,21).In general, rates of UTIs are higher among women than among men (15), with cystitis being the most prevalent UTI in women. It is noteworthy that the prevalence of quinolone resistance among E. coli strains causing cystitis is significantly higher than the prevalence of quinolone resistance among strains causing urinary parenchymatous infections such as prostatitis and pyelonephritis (2, 23). Velasco et al. (23) found that 20% of the isolates causing cystitis were resistant to ciprofloxacin, while only 8% of the invasive isolates causing UTIs had a resistant phenotype. Some studies suggest that resistance to the quinolones may be associated with a diminished virulence of the uropathogenic strains (16). Moreover, in a recent work (25), the prevalence of different genes encoding certain virulence factors among quinolone-resistant E. coli isolates causing cystitis and pyelonephritis in women was found to be lower than that among quinolone-susceptible strains.Both host and bacterial factors have been associated with the pathogenesis of these infections (9, 21). Thus, uropathogenic strains of E. coli are believed to display a variety of virulence properties that help them colonize host mucosal surfaces and circumvent host defenses to allow invasion of the normally sterile urinary tract (15,18,21). A number of virulence determinants have been related to the acquisition or development of UTIs. Among these factors, sidero...

To assess the utility of blood cultures in the management of uncomplicated pyelonephritis in women, we prospectively collected data from 583 cases. Discordant cases were defined as those for which the pathogens isolated from urine and from blood were different. We found that 97.6% of cases were nondiscordant. Clinical and microbiological evolution of infection did not differ between the 2 groups, and no changes of antibiotic therapy were required on the basis of blood culture results. Blood culture may not be routinely required for the evaluation of uncomplicated pyelonephritis in women.

DM prevalence among adults with TB in Barcelona is low and remained stable over the 14-year study period. However, TB patients with DM were potentially more infectious and their clinical management was more complicated.

The emergence and evolution of quinolone-resistant Escherichia coli in faeces of patients with prostatitis treated with high-dose oral ciprofloxacin for 1 month were studied. In 11 of 23 patients, from whom only quinolone-susceptible E. coli was isolated before treatment, quinolone-resistant strains, genetically distinct from the quinolone-susceptible ones, predominated during and just after therapy. Two months after treatment, these were completely displaced by quinolone-susceptible E. coli, genetically distinct from the E. coli isolated before and during therapy. Hence, during ciprofloxacin therapy, half of the patients were transiently colonized with new, quinolone-resistant strains of E. coli.

Patients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to a weight-banded nominal dose of 11, 14, 17, or 20 mg/kg/day levofloxacin (minimum, 750 mg) in combination with other second-line agents. A total of 101 patients were included in noncompartmental pharmacokinetic analyses. Respective median areas under the concentration-time curve from 0 to 24 h (AUC) were 109.49, 97.86, 145.33, and 207.04 μg · h/ml. Median maximum plasma concentration () were 11.90, 12.02, 14.86, and 19.17 μg/ml, respectively. Higher levofloxacin doses, up to 1,500 mg daily, resulted in higher exposures. (This study has been registered at ClinicalTrials.gov under identifier NCT01918397.).

.  Horcajada JP, Moreno I, Velasco M, Martínez JA, Moreno‐Martínez A, Barranco M, Vila J, Mensa J (Hospital Clínic Universitari‐IDIBAPS, Barcelona, Spain) Community‐acquired febrile urinary tract infection in diabetics could deserve a different management: a case–control study. J Intern Med 2003; 254: 280–286. Objective.  To investigate if there are relevant differences in clinical, microbiological and outcome characteristics of community‐acquired febrile urinary tract infection (UTI) between diabetic and nondiabetic patients. Design.  A prospectively matched case–control study. Setting.  An 800‐bed tertiary care university‐affiliated hospital. Subjects.  A total of 108 patients (54 diabetic and 54 nondiabetic patients matched by age and gender) admitted between January 1996 and September 1999 with febrile UTI. Methods.  Clinical, analytical, microbiological and outcome variables were analysed by means of McNemar test (categorical) or Wilcoxon matched pairs signed rank test (continuous). Results.  Mean age (SD) in both groups was 67.9 (14.4) years. In comparison with controls, diabetic patients were more likely to have fever without localizing symptoms (27% vs. 9%, P ≤ 0.0001), diminished consciousness level at admission (25% vs. 10%, P = 0.03), aetiological microorganism different from Escherichia coli (17% vs. 0, P = 0.0004), and quinolone‐resistant bacteria (17% vs. 3.7%, P = 0.07). Duration of fever after the onset of treatment was 1.75 (1) days in diabetics and 1.5 (1.1) days in nondiabetics (P = 0.17). However, diabetic patients had a longer hospitalization [5.2 (3.3) days] than nondiabetics [3.9 (2.6) days, P = 0.006]. Conclusions.  In diabetic patients, febrile UTIs have clinical and microbiological peculiarities that may have diagnostic and therapeutic implications.

BackgroundCurrent guidelines for treatment of multidrug-resistant tuberculosis (MDR-TB) are largely based on expert opinion and observational data. Fluoroquinolones remain an essential part of MDR-TB treatment, but the optimal dose of fluoroquinolones as part of the regimen has not been defined.Methods/designWe designed a randomized, blinded, phase II trial in MDR-TB patients comparing across levofloxacin doses of 11, 14, 17 and 20 mg/kg/day, all within an optimized background regimen. We assess pharmacokinetics, efficacy, safety and tolerability of regimens containing each of these doses. The primary efficacy outcome is time to culture conversion over the first 6 months of treatment. The study aims to determine the area under the curve (AUC) of the levofloxacin serum concentration in the 24 hours after dosing divided by the minimal inhibitory concentration of the patient’s Mycobacterium tuberculosis isolate that inhibits > 90% of organisms (AUC/MIC) that maximizes efficacy and the AUC that maximizes safety and tolerability in the context of an MDR-TB treatment regimen.DiscussionFluoroquinolones are an integral part of recommended MDR-TB regimens. Little is known about how to optimize dosing for efficacy while maintaining acceptable toxicity. This study will provide evidence to support revised dosing guidelines for the use of levofloxacin as part of combination regimens for treatment of MDR-TB. The novel methodology can be adapted to elucidate the effect of other single agents in multidrug antibiotic treatment regimens.Trial registrationClinicalTrials.gov, NCT01918397. Registered on 5 August 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2292-x) contains supplementary material, which is available to authorized users.