Moxifloxacin monotherapy versus ß-lactam mono- or combination therapy in hospitalized patients with community-acquired pneumonia.

OBJECTIVE: In this observational study, we compared the outcomes of moxifloxacin monotherapy as compared to ß-lactam monotherapy as well as ß-lactam combination therapy in patients with community-acquired pneumonia (CAP). METHODS: Patients recruited within the German Competence Network for CAP (CAPNETZ) were evaluated for treatment regimen. Primary outcome variables were six months overall mortality, pneumonia-related mortality according to clinical judgment and treatment failures (necessity for treatment change and death). RESULTS: Overall, 4091 patients (mean age 64.4±17.8 (range 18-101) years, 2433 male (59.5%)) were included. 2068 patients received moxifloxacin (n=365) or ß-lactam monotherapy (n=1703). 330 patients died within six months. After controlling for confounders in multivariate analysis, moxifloxacin monotherapy had higher survival as compared to ß-lactam monotherapy (hazard ratio for moxifloxacin 0.57, 95% CI 0.35-0.92). Multivariate analysis including interaction terms showed that the protective effect of moxifloxacin was not present for CRB-65 class 0 but increased with higher CRB-65 scores (HR 0.69, 95% CI 0.50-0.96). Regarding pneumonia-related death, moxifloxacin monotherapy was also protective in multivariate analysis (HR 0.36, 95% CI 0.13-0.99). Moxifloxacin was also significantly associated with less treatment failures (p<0.001). In addition, it was not inferior to combination ß-lactam treatment (p=0.062). CONCLUSIONS: In CRB-65 class 0 moxifloxacin was equivalent to ß-lactams. Our observations are in support of a use of moxifloxacin monotherapy in hospitalized patients with moderate CAP (CRB-65 classes 1 and 2).

Changes in Escherichia coli resistance patterns during and after antibiotic therapy: a longitudinal study among outpatients in Germany.

There is worldwide concern about the appearance and rise of bacterial resistance to commonly used antibiotics. Although the gut is an important reservoir for resistant Escherichia coli, data from large-scale epidemiological studies concerning the colonisation dynamics of the normal gut flora with resistant E. coli during and after antibiotic therapy are sparse. Accordingly, a large community-based study was conducted to ascertain changes in the prevalence of resistant E. coli during and after antibiotic treatment. Stool samples before, during and after antibiotic therapy were obtained from 541 patients (aged >/=40 years) with a febrile infection who attended a general practitioner in southern Germany. The MICs of commonly prescribed antibiotics for E. coli isolates from the stools were determined. The prevalence of resistance to the corresponding antibiotics rose from 18% to 38%, from 29% to 58% and from 33% to 67% during treatment with beta-lactam antibiotics, doxycycline and co-trimoxazole, respectively. Prevalences of resistance in the E. coli isolates also rose for other antibiotic classes. With the exception of co-trimoxazole resistance, prevalences of resistance returned to baseline levels in <2 weeks after the cessation of antibiotic therapy. Thus, there was a substantial, but rapidly reversible, increase in the prevalence of resistant E. coli isolates during antibiotic treatment.

Moxifloxacin prophylaxis in neutropenic patients.

OBJECTIVES: Recent studies have shown a beneficial impact of fluoroquinolones on infection-related morbidity and mortality for patients with haematological malignancies during neutropenia. Among the fluoroquinolones moxifloxacin currently provides one of the broadest spectra of antibacterial activity and may be suitable for prophylaxis during neutropenia. PATIENTS AND METHODS: In this controlled before and after observational study, moxifloxacin chemoprophylaxis was used during prolonged neutropenia in haemato-oncological patients (period 2; 282 episodes). Data were compared with two periods with levofloxacin prophylaxis, one preceding period (period 1; 399 episodes) and a post-observational period (period 3; 53 episodes). Endpoints for evaluation were the rates of Gram-negative and Gram-positive bacteraemia and infection-related mortality. RESULTS: We found similar survival rates as compared with levofloxacin. The rate of Gram-negative bacteraemia was higher during prophylaxis with moxifloxacin (11%) when compared with levofloxacin (6% for period 1 and 6% for period 3). In addition we observed a marked increase in diarrhoea associated with Clostridium difficile toxin A (CDAD) after a formula change from levofloxacin to moxifloxacin (attack rate 6% versus 33%). A decrease was attained after changing back to levofloxacin and reinforcing hygienic measures (13%). CONCLUSIONS: During moxifloxacin prophylaxis, we observed a significantly increased incidence of Gram-negative bacteraemia and CDAD. Careful attention must be paid not to trade the particularly beneficial effects of fluoroquinolones in the neutropenic setting for such disadvantageous effects. Until further data are obtained, caution is warranted when applying fluoroquinolones with high anaerobic activity in the neutropenic setting.

Prevalence of resistance to clarithromycin and its clinical impact on the efficacy of Helicobacter pylori eradication.

BACKGROUND: Triple therapy with a proton-pump inhibitor (PPI) in combination with metronidazole and clarithromycin is the method of choice for eradication of Helicobacter pylori. Failures have been primarily blamed on the development of resistance to clarithromycin. The present study investigated the prevalence and clinical significance of resistance to clarithromycin and metronidazole in determining therapeutic success of both triple therapy as a primary eradication method and high-dose dual therapy in non-responders. METHODS: On the basis of prior therapy, H. pylori-positive patients were assigned to one of two groups in the present prospective study. Group A (n = 93) included patients who had not undergone any prior eradication treatment, whereas group B (n = 15) consisted of patients who had received clarithromycin but in whom eradication had been unsuccessful. All patients underwent endoscopy with biopsy for bacterial culture and resistance studies. Patients in group A were treated with a 7-day regimen of pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily), and clarithromycin (250 mg twice daily), whereas those in group B received omeprazole (40 mg three times a day) and amoxycillin (1000 mg three times a day ) for 14 days. Success of the eradication treatment was ascertained by means of the 13C urea breath test. RESULTS: In group A resistance to clarithromycin and metronidazole was identified in 3 patients (4.9%) and in 14 patients (22.9%), respectively. Eradication proved successful in 78 of 84 patients (92.6%) followed up. Two of the 3 patients with primary clarithromycin resistance and 1 of the 14 patients with metronidazole resistance did not respond to treatment. In group B isolated or combined resistance to clarithromycin was found in seven patients, whereas another four showed isolated resistance to metronidazole. Eradication proved successful in 10 of 13 controlled patients (76.9%) followed up, and only 2 patients reported severe side effects. CONCLUSION: Determination of antibiotic resistance before initiating therapy is not necessary, since primary resistance to clarithromycin is rare. The Italian triple therapy remains a highly effective primary therapeutic method. Further, routine determination of resistance in non-responders also seems to be superfluous because high-dose dual therapy is an effective and well-tolerated second-line therapy regardless of the patients' resistance status.

Influence of hemodilution on cefuroxime levels and bacterial contamination of intra- and postoperative processed wound blood during hip replacement.

MATERIALS AND METHODS: In a prospective randomized study we investigated the effect of hemodilution on cefuroxime levels and bacterial contamination of processed shed blood during hip arthroplasty. 10 patients received cefuroxime 1,5 g as single shot prophylaxis before (group A), 10 after hemodilution (15 ml/KG) (group B). Cefuroxime levels in serum 1 h after administration, at the end of operation, after 12 h and in drainage-blood after 12 h were assessed by HPLC. Bacteriological study was performed from collecting bags (Vacufix), wound drainage blood and processed red blood cell concentrates, using pour plate technique and broth culture enrichment. RESULTS AND DISCUSSION: Mean concentrations of cefuroxime were higher in group B than group A, but differed not significantly. No bacterial contamination was found in collecting bags and wound drainages in both groups. Processed red cell concentrates in group B showed no growth. In group A, however, 3/10 were contaminated with < or = CFU/ml of coagulase-negative Staphylococcus, Staphylococcus epidermidis and Propionibacterium acnes. The differences between groups did not reach the level of statistical significance and could not be related to lower cefuroxime levels. No wound infection occurred in either group.

Comparative efficacy of ciprofloxacin, ceftazidime and gentamicin, given alone or in combination, in a model of experimental septicemia due to Klebsiella pneumoniae in neutropenic mice.

The therapeutic efficacy of ciprofloxacin, used alone and in combination with either ceftazidime or gentamicin, was evaluated in a model of experimental Klebsiella pneumoniae septicemia in neutropenic mice. Therapeutic results were compared to those achieved by treatment with ceftazidime or gentamicin alone, as well as their combination. Infections were induced by i.v. injection of two strains of K. pneumoniae. Therapy with i.m. antibiotics was performed in 8 h intervals for a total of 13 doses, and survival rates were recorded at the end of treatment as well as seven days later. Ciprofloxacin alone proved to be significantly more effective than ceftazidime and gentamicin, producing survival rates similar to the combination of ceftazidime plus gentamicin. Bacterial counts of spleens and blood confirmed the superior bactericidal activity of ciprofloxacin. Except for the combination of ciprofloxacin with ceftazidime, there was no apparent advantage of combinations of ciprofloxacin with the other agents compared to ciprofloxacin alone. These data suggest a high in vivo activity of ciprofloxacin in systemic infection due to K. pneumoniae.

Comparative efficacy of different beta-lactam antibiotics and gentamicin in Klebsiella pneumoniae septicaemia in neutropenic mice.

The in-vivo activity of ceftazidime, cefotetan, imipenem/cilastatin, piperacillin and gentamicin against two strains of Klebsiella pneumoniae was evaluated in a model of experimental septicaemia in neuropenic mice. Single agent therapy with the aminoglycoside was highly effective against both strains. Among the beta-lactams, ceftazidime and cefotetan were nearly as active as gentamicin, whereas imipenem/cilastatin was slightly less effective, and the results achieved with piperacillin were markedly inferior.

[Ciprofloxacin and cefotaxim: pharmacokinetic and therapeutic effectiveness in E. coli pyelonephritis in rats]. / Ciprofloxacin und Cefotaxim: Pharmakokinetik und therapeutische Effektivität bei der E. coli-Pyelonephritis der Ratte.

Ciprofloxacin was tested in the acute and chronic experimental E.coli pyelonephritis in rats. Its therapeutic efficacy was compared with that of cefotaxime. In the acute pyelonephritis increasing doses resulted in increasing elimination of bacteria from the kidneys. Ciprofloxacin and cefotaxime showed no difference in the efficiency in therapy of the acute pyelonephritis. In chronic pyelonephritis ciprofloxacin proved to be more effective than cefotaxime in spite of identical in vitro activity. Pharmacokinetic data showed that ciprofloxacin was eliminated more slowly than cefotaxime. The long serum half-life and the high volume of distribution could be responsible for the high therapeutic efficacy and could outweigh the disadvantage of metabolic instability.

Ceftazidime, ceftizoxime, cefotaxime and HR 221 in experimental chronic Escherichia coli pyelonephritis in rats.

The therapeutic efficacy and pharmacokinetics of the cephalosporins ceftazidime, ceftizoxime, cefotaxime and HR 221 were studied in animal experiments. The animal model used was experimental estrogen-induced or non-induced chronic Escherichia coli pyelonephritis in rats. The animals were treated with 5 mg cephalosporin/kg twice daily for one week. Each of the cephalosporins tested led to a significant decrease in renal bacterial counts, in spite of the low doses given. Ceftazidime was significantly more active than HR 221 in both experimental models, although the serum levels of HR 221 were higher and were maintained for a longer period of time than those of ceftazidime. Differences in pharmacokinetic properties (influenced by metabolic stability and protein binding) could be the reason for the differences in therapeutic activity, since the in vitro antimicrobial activity of each of the cephalosporins tested was very similar against the test strain.