Clinical efficacy of moxifloxacin versus comparator therapies for community-acquired pneumonia caused by Legionella spp.

The aim of this study was to compare outcomes for patients with community-acquired pneumonia (CAP) caused by Legionella spp. following treatment with moxifloxacin or a range of comparator antimicrobial agents. Data were pooled from four sequential I.V./P.O. trials of moxifloxacin in the treatment of CAP. Comparators were ceftriaxone +/- erythromycin, amoxicillin/clavulanate +/- clarithromycin, trovafloxacin, levofloxacin, or ceftriaxone + levofloxacin. Legionella infection was diagnosed by culture, urine antigen testing and/or serology. Clinical success rates for the efficacy-valid (per protocol) populations were recorded at the test-of-cure visit (5-30 days post-therapy). Severity of CAP was determined using the modified American Thoracic Society criteria.Of 1786 efficacy-valid patients, 33 (1.8%) had documented infection with Legionella spp. (moxifloxacin: n=13; comparator: n=20). Of these, 30 cases were identified by serology and/or urine antigen detection and 3 by respiratory culture. The success rate of moxifloxacin vs. comparator therapy was 92.3% vs. 80.0% for the I.V./P.O. trials.Sequential (I.V./P.O.) moxifloxacin demonstrated clinical efficacy that was at least as good as that of comparator treatments for the treatment of CAP due to Legionella.

The clinical impact of macrolide resistance in pneumococcal respiratory infections.

By the 1960s, several reports of bacteria with reduced susceptibility to antibiotics were published. In recent years, the problem of antibiotic resistance has magnified. In the treatment of respiratory tract infections, the development of resistance is of particular concern; 67% of antibiotic use in adults and 87% in children is for the treatment of such infections. Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and is a frequently isolated bacterial species in patients with other respiratory tract infections. Increasing levels of resistance may have important implications in the clinical setting. Physicians need to consider local susceptibility data, in addition to the pharmacokinetic and pharmacodynamic features of compounds, when selecting appropriate antibiotics for the treatment of bacterial infections.

Gemifloxacin versus amoxicillin/clavulanate in the treatment of acute exacerbations of chronic bronchitis. The 070 Clinical Study group.

Six hundred patients were evaluated in this randomized, double-blind, double-dummy, multicenter, parallel-group study comparing the efficacy and safety of gemifloxacin (320 mg once-daily for 5 days) and amoxicillin/clavulanate (500/125 mg three-times daily for 7 days) for the treatment of acute exacerbations of chronic bronchitis (AECB). Of note, more than 90% of study participants had stage 2 disease at study entry. The two drugs were found to be equally effective, with clinical success rates of 93.6% for gemifloxacin and 93.2% on amoxicillin/clavulanate (95% CI -3.9 to 4.6). Bacteriological success rates favored gemifloxacin (90.9% compared with 79.5% for amoxicillin/clavulanate; 95% CI -3.3 to 26.0); however, this difference was not statistically significant. Gemifloxacin and amoxicillin/clavulanate were both well tolerated. In summary, gemifloxacin was found to be well tolerated and effective for the treatment of AECB, suggesting it is well suited for empirical treatment of this common respiratory condition in the current clinical environment.

Clinical perspectives on the management of community-acquired pneumonia.

The management of community-acquired pneumonia requires the physician to start antibiotic treatment before the results of the sensitivity tests are known. To make a rational choice of antibiotic, a knowledge of the epidemiology of the disease is required with data on the susceptibility of the main pathogens to various antibiotics. Care must be taken to differentiate the "typical" from the "atypical" pneumonia. Increasing resistance among pneumococci to penicillin is causing considerable concern and, although increasing the dose is a strategy that currently works, a point will be reached in the future where new antibiotics will be required.

[Loss of antibiotic sensitivity of Pseudomonas aeruginosa strains during treatment]. / Pérdida de sensibilidad a los antibióticos de cepas de Pseudomonas aeruginosa en el curso del tratamiento.

BACKGROUND: Loss of sensitivity to betalactamic, quinolones and aminoglucoside antibiotics has been described during treatment of infections produced by strains of Pseudomonas aeruginosa. Sixteen nosocomial strains isolated over a year during which sensitivity to one or several antibiotics of the above mentioned groups had been lost during the course of treatment were studied. METHODS: The strains were identified by conventional techniques. Sensitivity to antibiotics was studied by determination of the minimum inhibitory concentration in solid medium, according to the guidelines of the National Committee for Clinical Laboratory Standards. Plasmidic beta-lactamases were identified by analytic isoelectric focusing. Hyperproduction of chromosomic lactamase was studied by a qualitative technique. The 0 antigens were studied against rabbit antisera. The pyocinetype was determined according to the Fyfe method. Plasmids were detected by alkaline lysis extraction and electrophoresis in agarose gel. RESULTS: The 16 strains in which changes in sensitivity were observed during the course of treatment represent 4.47% of all P. aeruginosa isolates during one year. Loss of sensitivity to betalactamic antibiotics was observed in 10 strains, in one to aminoglucosides, in two to ciprofloxacin, simultaneously to aminoglucosides and ciprofloxacin in one and to betalactamic and ciprofloxacin in another two. Six of the 13 patients (46%) required a change in antibiotic treatment. CONCLUSIONS: The convenience of following the sensitivity of the strains of Pseudomonas aeruginosa isolated in a patients is suggested to thereby avoid therapeutic failure and the potential danger of clonal dissemination of the strains which have lost sensitivity.

Resistant pneumococci: a renewed threat in respiratory infections.

The emergence of penicillin-resistant Streptococcus pneumoniae (PRSP) is an international problem which has been compounded by the development of high-level, multiple resistance to other beta-lactam antibiotics. Resistance develops in a 'step-wise' but unpredictable manner due to the mutation of penicillin-binding proteins (PBP). This results in a high degree of heterogeneity between bacterial strains. Such mutations can result in the rapid emergence of antibiotic resistance, including extended-spectrum cephalosporins, with reported minimum inhibitory concentration (MIC) values of up to 32 mg/l. The effective treatment of diseases caused by such organisms is dependent upon rapid assessment of antibiotic sensitivities. Therefore, MIC values of a range of antibiotics must be determined in cases of treatment failure and in serious pneumococcal infections. However, pharmacokinetic properties, as determined by the inhibitory quotient, which reflect drug concentrations attainable in different tissues, should also be considered. Beta-lactam antibiotics with good inhibitory activity against pneumococci include: amoxycillin, cefotaxime, ceftriaxone, cefpirome and imipenem. Nevertheless, as the prevalence of PRSP strains is likely to increase, new therapeutic strategies may have to be adopted.

Ciprofloxacin and trimethoprim-sulfamethoxazole versus placebo in acute uncomplicated Salmonella enteritis: a double-blind trial.

The role of ciprofloxacin and trimethoprim-sulfamethoxazole (TMP-SMZ) was evaluated in empiric treatment of uncomplicated Salmonella enteritis in a comparative, double-blind trial. Patients were randomized to receive ciprofloxacin (500 mg), TMP-SMZ (160/800 mg), or placebo orally twice daily for 5 days. There were 65 evaluatable patients with acute, uncomplicated, culture-confirmed Salmonella enteritis. Duration of diarrhea, abdominal pain, or vomiting and time to defervescence were not significantly different for patients treated with ciprofloxacin, TMP-SMZ, or placebo; there also were no significant differences with respect to full resolution of symptoms for ciprofloxacin versus placebo (point estimate, 0.2 days; 95% confidence interval [CI], -0.5 to 0.9 days) or for TMP-SMZ versus placebo (point estimate, 0.2 days; 95% CI, -1.0 to 0.6 days). The rate of clearance of salmonellae from stools was not significantly different among the groups.

[Penicillin-resistant pneumococci and the empirical use of penicillins in the treatment of community-acquired acute pneumonia]. / Neumococos resistentes a penicilina y uso empírico de penicilinas en el tratamiento de la neumonía aguda extrahospitalaria.

The prevalence of penicillin-resistant pneumococci in our environment has raised questions about the effectiveness of penicillin as empiric treatment for community-acquired pneumonia cases. We followed prospectively all patients with community-acquired pneumonia from February 1989 through January 1990. We also reviewed retrospectively the treatment and evolution of all patients with confirmed pneumococcal pneumonia diagnosed between January 1988 and January 1990. A total of 115 patients with probable pneumococcal pneumonia were prospectively followed-up. Seventy-nine were treated with penicillin (benzyl- and aminopenicillin), and the remaining patients with macrolides, cephalosporin drugs or both. Five patients died (4%). There is no significant differences between mortality in penicillin-treated patients (2 cases) when compared to patients with other treatments (3 cases). Twenty-three patients have confirmed pneumococcal pneumonia. Among them, 8 (24%) had penicillin-resistant pneumococci (5 strains with MIC: 0.12-1 microgram/ml; 3 strains with MIC: 2 micrograms/ml). No differences were recorded regarding demographic data, predisposing conditions, underlying diseases, severity of pneumonia or the outcome of treatment between penicillin and non-penicillin treatment groups. Also, no differences were seen in clinical response and mortality when patients with pneumonia due to penicillin-resistant pneumococci treated with penicillin were compared to the ones treated with other drugs. In two patients, initially treated with erythromycin, progression of the pneumonia was recorded. Erythromycin resistant pneumococci (MIC greater than 8 micrograms/ml) were recovered from transthoracic needle biopsy. Both patients recovered well when beta-lactam antibiotics were prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)

Single-dose antibiotic prophylaxis in patients at high risk for infection in biliary surgery: a prospective and randomized study comparing cefonicid with mezlocillin.

The usefulness of antibiotic prophylaxis in biliary surgery is well established. When antibiotic prophylaxis is not used, wound infection rates after biliary surgery range from 10% to 25%. With antibiotic prophylaxis, the rates can be reduced to less than 5%. Three questions are still controversial: Do all patients undergoing biliary surgery require antibiotic prophylaxis? What is the ideal antibiotic for use in biliary surgery? What should be the duration of antibiotic prophylaxis? In this study we prospectively evaluated the efficacy of a single dose of antibiotic prophylaxis in biliary surgery, administered to patients at high risk for infection, in a trial comparing cefonicid (a cephalosporin with a long half-life) with mezlocillin (a broad-spectrum ureidopenicillin).

Efficacy of orally administered penicillin V for prophylaxis of experimentally induced streptococcal endocarditis.

Four oral penicillin V regimens were compared for the ability to prevent Streptococcus sanguis infection of experimentally induced valvular heart lesions in rabbits. Challenge doses of 10(4), 10(6), and 10(8) CFU of a penicillin-susceptible strain of S. sanguis were used in this study. Measured by recovery of test organisms from endocardial lesions, the lowest-concentration inoculum was infective for 53% of the recipients; the higher-concentration inocula were infective for all recipients. A single-oral-dose penicillin V regimen (36 mg/kg of body weight) prevented endocarditis when rabbits were challenged with 10(4) CFU, but protection diminished with increasing inoculum concentrations. In contrast, addition of a second penicillin V dose (18 mg/kg of body weight) administered with a 7-h interval between doses achieved fully effective prophylaxis against even the highest inoculum tested (10(8) CFU). A repeated set of experiments in which half the dose of penicillin V was administered showed significantly reduced protection against S. sanguis endocarditis.