OBJECTIVE: Uncomplicated cystitis in women is among the most frequent infections in the community setting. The German results of the international ARESC Study are reported concerning clinical aspects, epidemiology, and antimicrobial susceptibility of uropathogens. PATIENTS AND METHODS: Patients between 18 and 65 years of age with symptoms of uncomplicated cystitis were consecutively enrolled and investigated clinically including urinalysis and urine culture. Uropathogens were identified and their susceptibility was tested for nine antimicrobials RESULTS: In Germany a total of 442 patients were enrolled and 412 were eligible. A positive urine culture (cfu>/=10(4)/ml) was found in 335 (81.3%); 325 (97.1%) of them had a monoinfection. A total of 317 uropathogens were further analyzed in a central laboratory (Genua). Escherichia coli was the most frequent (76.7%), followed by Proteus mirabilis (4.7%), Staphylococcus saprophyticus (2.8%), Klebsiella pneumoniae (2.5%), enterococci (2.5%), and Staphylococcus aureus (2.2%). E. coli showed the highest rate of susceptibility to fosfomycin (97.9%) followed by mecillinam (97.5%), nitrofurantoin (95.4%), and ciprofloxacin (95.4%). The lowest rate was found for ampicillin (59.2%) followed by cotrimoxazole (74.0%). For the total spectrum the order was fosfomycin (96.1%), mecillinam (97.5%), ciprofloxacin (92.3%), and nitrofurantoin (86.3%). The lowest rates were found again for ampicillin (56.6%) and cotrimoxazole (73.9%). CONCLUSIONS: Fosfomycin, mecillinam (not available in Germany), and nitrofurantoin have preserved their in vitro activity and are suitable for empiric therapy. Because of increasing resistance rates cotrimoxazole (trimethoprim) and fluoroquinolones are generally not recommended as first-choice drugs for empiric therapy of female patients with uncomplicated cystitis.

The aim of the study was to investigate the urinary bactericidal titers (UBTs) and 24 hours area under the UBT versus time curve (AUBT) of intravenuous doripenem (500mg q8h), a new carbapenem, versus intravenous levofloxacin (250mg q 24h) in patients with complicated urinary tract infections (cUTIs) or pyelonephritis. UBTs and AUBTs are pharmacokinetic/pharmacodynamic parameters able to reflect the activity of an antimicrobial substance in the urine. Doripenem and levofloxacin show comparable urinary excretion of approximately 80% and are therefore registered for the treatment of UTI. In order to assess and compare the urinary antimicrobial activity of both substances, UBTs were investigated in 24 patients (10 treated with doripenem and 14 with levofloxacin) for 31 uropathogens and one control strain. Eight strains were tested in all patients and 27 only in the urine of the corresponding patient. Median UBTs (AUBTs) of doripenem for the uropathogens tested ranged between 1.5 and 65,536 (224 and 909,312) and were significantly higher than median UBTs (AUBTs) of levofloxacin ranging between 0 and 128 (0 and 2,208). Eight microbiological failures were observed, three after doripenem treatment and five after levofloxacin treatment. For levofloxacin microbiological failures correlated well with low UBTs and AUBTs, whereas for doripenem there was no correlation. From this study a calculated target attainment rate for levofloxacin predicting therapeutic success in patients with complicated UTI approximated mean UBTs of 100 over 24h or AUBTs of 2,240. Doripenem demonstrated excellent urinary bactericidal activity with the dose administered and appears to be a good alternative in the empiric treatment of cUTI.

Antibiotic resistance nowadays plays an important role in the treatment of uncomplicated and complicated urinary tract infections (UTIs). In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI substances with activity against bacteria harbouring common resistance mechanisms are investigated. Additionally pharmacokinetic/ pharmacodynamic parameters are used to improve dosing strategies.

Bacterial urinary tract infections (UTI) are frequently found in the outpatient as well as in the nosocomial setting. The bacterial UTI can be stratified into uncomplicated and complicated UTI. Antibiotic resistance is continuously increasing in uncomplicated as well as complicated UTI. In uncomplicated UTI efforts are made to use antibiotic substances exclusively for this indication. In complicated UTI as broad spectrum antibiotics are increasingly used, the higher the antimicrobial resistance rates are reported. There are two predominant aims in the antimicrobial treatment of both uncomplicated and complicated UTI: 1.) rapid and effective response to therapy, prevention of complications and prevention of recurrence in the individual patient treated, and 2.) prevention of emergence of resistance to anti-infective agents in the microbial environment. The use of antibiotics has to keep up with the continuous change in antimicrobial resistance and the tailored needs in the individual patient. Antibiotic substances therefore need to become evaluated for each indication and continuously followed for clinical usage. The knowledge of structure-activity relationships of antimicrobial substances and bacterial resistance mechanisms to antibiotics help to use antibiotics better in daily routine and design new derivatives and substances. The aim of this review is to describe the chemistry and structure-activity relationships of current antibiotics and promising substances in development for the treatment of UTI.

The spectrum of chronic bacterial prostatitis (CBP) comprises Gram-negative, Gram-positive and atypical pathogens. Because of its broad spectrum of activity, moxifloxacin might be a suitable antibiotic for the treatment of CBP. In this pharmacokinetic study, plasma concentrations and the penetration of moxifloxacin into prostatic fluid and ejaculate were investigated. Twelve healthy male volunteers received a single oral dose of 400mg moxifloxacin and at the same time received 3.24g of iohexol intravenously to assess urinary contamination of prostatic fluid and ejaculate. Plasma concentrations were determined at 0, 0.5, 1, 2, 3 and 4h and prostatic fluid and ejaculate (mean+/-standard deviation (S.D.)) were determined at 3.5+/-0.4h and 3.6+/-0.4h, respectively, following administration of drugs. Urinary concentrations were determined in the urine collected from 0-4.5h. Concentrations of moxifloxacin and iohexol in plasma, secretions and urine were determined by high-performance liquid chromatography. The mean+/-S.D. peak plasma concentration of moxifloxacin was 2.8+/-0.5mg/L observed after 1.6+/-0.9h. In prostatic fluid, the concentration of moxifloxacin was 3.8+/-1.2mg/L and the prostatic fluid/plasma ratio was 1.6+/-0.5. In ejaculate, the concentration was 2.5+/-0.7mg/L and the ejaculate/plasma ratio was 1.0+/-0.2. Moxifloxacin concentrations in prostatic fluid were ca. 60%(P<0.05) higher than in plasma and concentrations in ejaculate were approximately the same as in plasma. Therefore, moxifloxacin might be a good alternative for the treatment of CBP, but further studies are warranted to establish this indication.

We report the largest documented healthcare-associated outbreak of Panton-Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus (PVL(+) MRSA) in Europe. Six index patients from three long-term care facilities (LTCFs) were screened positive for PVL(+) MRSA in 2004 on admission to a community hospital in Germany. The purpose of this prospective study was to describe the prevalence of PVL(+) MRSA in the LTCFs before and after infection control interventions. Screening for MRSA with or without PVL was performed in all three LTCFs in 2004 [453 residents, 240 healthcare workers (HCWs)] and 2005 (440 residents, 192 HCWs). Swabs from anterior nares and wounds, if applicable, were collected. Colonised residents and staff were treated with mupirocin nasal ointment and topical antiseptics, and staff were provided with hygiene education. Total MRSA carrier rate of residents and HCWs in 2004 was 11.3%(PVL(+) MRSA 9.1%, PVL(-) MRSA 2.2%). There were comparable carrier rates between residents and HCWs in each LTCF. All PVL(+) MRSA isolates were of clonal origin (MLST 22) representing a novel spa sequence type t310. A decrease in total MRSA prevalence (from 11.3 to 5.5%) and PVL(+) MRSA (from 9.1 to 3.3%) was observed in 2005. The rate of PVL(-) MRSA remained unaffected. No symptomatic skin infections were noted among residents or HCWs. In this outbreak incomplete control of PVL(+) MRSA presumably resulted from difficult and delayed detection and decolonisation of carriers, incomplete compliance with control measures and lack of enforcement by public health authorities.

12 volunteers received a single oral dose of 1,000 mg ciprofloxacin XR versus 500 mg levofloxacin to assess urinary bactericidal titers (UBT) against common uropathogens. Areas under UBT-time curves were significantly different for P. mirabilis in favour of ciprofloxacin XR, and for staphylococci in favour of levofloxacin.

The new extended-release formulation of ciprofloxacin (ciprofloxacin XR) was designed for once-daily administration in the treatment of urinary tract infection (UTI). The aim of this study was to compare concentrations in plasma, urinary excretion (UE) and pharmacokinetic parameters of ciprofloxacin XR (1000mg) versus those of levofloxacin (500mg) in healthy volunteers receiving a single oral dose. In this randomised crossover study, 12 volunteers (6 males, 6 females) received a single oral dose of 1000mg ciprofloxacin XR or 500mg levofloxacin to assess the concentrations (by high-pressure liquid chromatography) in plasma up to 32h and the UE at intervals up to 36h. The following pharmacokinetic parameters were studied: C(max), t(max), t(1/2), AUC(plasma0-->infinity), AUC(plasma0-->last), Cl(ren), maximal urinary concentration (U(max)), AUC(urine0-->last) and UE. Both fluoroquinolones were well tolerated. The plasma concentrations of levofloxacin were significantly higher than those of ciprofloxacin XR throughout the study period. The urinary concentrations of ciprofloxacin XR were significantly higher than those of levofloxacin in the first collection interval (0-4h), whereas the concentrations of levofloxacin were significantly higher than those of ciprofloxacin XR in the five last collection intervals (12-36h). The median proportions of cumulative renal excretion of the administered dose of the parent drug up to 36h were 43.1% for ciprofloxacin XR (range, 13.7-50.8%; mean+/-standard deviation (S.D.), 40.5+/-9.9%) and 79.8% for levofloxacin (range, 74.0-88.2%; mean+/-S.D., 80.4+/-5.5%). C(max), AUC(plasma0-->infinity), AUC(plasma0-->last) and UE were statistically significantly higher in the levofloxacin than in the ciprofloxacin XR phase; t(max), Cl(ren) and U(max) were statistically significantly higher in the ciprofloxacin XR phase than in the levofloxacin phase; and AUC(urine0-->last) and t(1/2) were not statistically different. After an oral administration of ciprofloxacin XR 1000mg and levofloxacin 500mg, C(max) and AUC(plasma0-->infinity) were significantly higher in the levofloxacin phase. UE of ciprofloxacin XR 1000mg once daily, however, was equivalent to that of levofloxacin 500mg, and overall comparable urinary concentrations and AUC(urine) were reached by both drugs. Therefore, it can be assumed that the two doses investigated can be considered equivalent for the treatment of UTI.

OBJECTIVES: Transurethral resection of the prostate (TUR-P) is one of the most frequent urological procedures. The efficacy of a prophylactic single dose of levofloxacin vs. trimethoprim/sulfamethoxazole (TMP/SMZ) vs. a control group, receiving no antibiotic prophylaxis, in patients undergoing TUR-P was investigated in a multicentre study. The aims were to assess the rate of bacteriuria (cfu> or =10(4)/ml) 5 to 7 days, and 3 to 5 weeks after TUR-P, as well as postoperative complications. METHODS: The study was prospective, randomized, multicentric, open and comparative. Patients without bacteriuria (cfu<10(4)/ml) scheduled for TUR-P and not having received antibiotics prior within four days were enclosed. Patients received an oral single dose prophylaxis with either 500 mg levofloxacin, or 320/1600 mg TMP/SMZ, or no prophylaxis according to a 2:2:1 randomization. Clinical examination of the patients and urine culture were performed prior to, 5 to 7 days and 3 to 5 weeks after TUR-P. RESULTS: 14 urological centres throughout Germany recruited 400 patients. 376 patients were evaluable until day 5 to 7, 339 until week 3 to 5. Overall bacteriuria rate at day 5 to 7 was 22%(levofloxacin 21%; TMP/SMZ 20%; control group 30%). Bacteriuria rate at week 3 to 5 was 28%(levofloxacin 26%; TMP/SMZ 26%; control group 36%). Complication rate at week 3 to 5 was 10%(levofloxacin 8%; TMP/SMZ 10%; control group 16%). The rates of postoperative bacteriuria ranged widely between centers (0%-75%). Statistically significant (p<0.05) risk factors for bacteriuria (range) were qualification of surgeon (19%-37%), presence of a suprapubic catheter (22%-34%), disconnection of the closed drainage system (25%-52%), operating time (12%-31%) and operative centre (0%-75%). Total antibiotic consumption (for prophylaxis and treatment) in the control group was higher and more expensive than in groups with antibiotic prophylaxis (6.9 vs. 5.0 doses/patient; 24.9 vs. 19.7 /patient)(p<0.0001). Postoperative complications in patients with bacteriuria (cfu> or =10(4)/ml) were more frequent than in non bacteriuric (cfu<10(4)/ml) patients (17% vs. 8%)(p<0.01). CONCLUSIONS: It is debatable whether postoperative bacteriuria is the key parameter to define efficacy of antimicrobial prophylaxis in patients undergoing TUR-P. The rate of bacteriuria, however, correlated well with the overall rate of postoperative complications. Therefore, it seems reasonable to lower the rate of bacteriuria by prophylaxis. Since patients without antibiotic prophylaxis received at the end even more antibiotic doses than patients with prophylaxis, the overall selection pressure by antibiotic usage can obviously not be lowered by resigning prophylaxis. Therefore we conclude that at least patients at risk should receive antibiotic prophylaxis prior to TUR-P.