In vitro susceptibility of 33 clinical case isolates of Xanthomonas maltophilia. Inconsistent correlation of agar dilution and of disk diffusion test results.

Xanthomonas maltophilia is an emerging nosocomial pathogen, possibly selected by a changing antimicrobial usage and patient population. In the present study, we tested the susceptibility of 33 recent clinical case isolates to 12 commonly employed antimicrobials. Trimethoprim-sulfamethoxazole (1:19 ratio) and doxycycline were uniformly the most active agents; ciprofloxacin and fleroxacin were slightly less active and, along with tetracycline and ceftazidime, more variable in their potency. Interestingly, the disk diffusion method routinely overstated the activity of ciprofloxacin (12% very major errors, 58% minor errors). The present in vitro data and the hitherto accumulated clinical experience suggest that in the absence of unequivocal clinical efficacy of ciprofloxacin against this increasingly recognized nosocomial pathogen, the decision to use ciprofloxacin or any other fluoroquinolone against these pathogens should rely preferentially on the dilution susceptibility test method results. In contrast, the present study confirms the excellent predictive value of trimethoprim-sulfamethoxazole, tetracycline, and fleroxacin disks as well as the higher (9% minor errors) inhibitory activity of these drugs. Hence, pending the elaboration of clinical efficacy data of alternative antimicrobial agents against X. maltophilia infections, trimethoprim-sulfamethoxazole remains a sound therapeutic choice.

Interlaboratory variations of fluoroquinolone susceptibility testing. An international study to validate the quality of microbiology results reported during the fleroxacin clinical trials.

Fleroxacin, a newer fluoroquinolone, has been investigated extensively in worldwide clinical trials by laboratories using a variety of in vitro susceptibility testing methods. These methods differ in their technical details, leading to applied interpretive criteria that can also differ from nation to nation and from method to method. This retrospective three-phase investigation was designed to assess the disk diffusion and minimum inhibitory concentration (MIC) result variations produced by European laboratories participating in fleroxacin clinical trials as compared with the results of a reference laboratory performing National Committee for Clinical Laboratory Standards (NCCLS) tests. In "phase I," 105 clinical trial strains (1988-1989) from six European investigators were processed by the reference laboratory. In comparison of participant and reference laboratory zone diameters, absolute qualitative agreement was 88.7% for the approved NCCLS interpretive criteria and 94.8% for the criteria used in the fleroxacin urinary tract infection clinical trials. Only three false-susceptible results (3.1%) were reported by the investigators. In the remaining phases of this study (unknown challenge strains and contemporary clinical isolates), the investigator laboratory zone diameters and MICs were within limits of acceptable test variation, that is, +/- 4 mm by disk diffusion and +/- 1 log2 dilution step by the MIC method. For laboratories using the German (DIN) and French (SFM) methods, however, a trend toward larger zones was observed. The greatest variation between participant and NCCLS results was produced when fastidious isolates such as Haemophilus influenzae (significantly smaller zone diameters) were tested. In general, the European fleroxacin clinical trial laboratory results (organism identification and susceptibility tests) could be considered comparable to data produced with NCCLS reference methods, indicating that clinical trial results from wider sources could be used for drug registry by the US Food and Drug Administration (FDA) or by other national agencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefetamet pivoxil in the treatment of uncomplicated gonorrhea.

We studied the efficacy and safety of cefetamet pivoxil (CAT), an oral aminothiazolyl cephalosporin, in a series of open, comparative multicenter studies in 207 women (four study centers) with uncomplicated gonorrhea, and summarized and pooled the results with those of earlier open dose-finding trials (360 men; six study centers). We compared single-dose treatment regimen of CAT--over the range of 400-1500 mg--with spectinomycin, thiamphenicol, ampicillin, or amoxicillin plus probenecid. The overall cure rates were 100% in 88 women treated with 1500 mg CAT and in 137 men treated with 1200 or 1500 mg CAT, 98% (114 of 116 men) in those treated with 800 or 1000 mg CAT, and 93% (42 of 45 men) in those treated with 400 or 500 mg CAT; the composite cure rate of the comparators was 97%. The tolerability of CAT (n = 428) compared favorably (1.8% adverse events) with that of the standard drugs (n = 139) (4.3% adverse events). Single-dose treatment with 1500 mg CAT is effective and safe in adults with uncomplicated gonorrhea.

Legionella bozemanii, an elusive agent of fatal cavitary pneumonia.

A 67-year-old patient died of Legionella bozemanii pneumonia with negative urinary antigen and negative serology. Cystic lesions in pneumonia of unknown origin should lead to the differential diagnosis of L. bozemanii infections.

In vitro activity of fleroxacin against aerobic gram-positive bacteria including Corynebacterium jeikeium.

Fleroxacin (Ro 23-6240, AM-833), a new fluoro-4-quinolone, was tested in vitro against 273 gram-positive clinical isolates. Norfloxacin, a quinolone mostly used in urinary tract infections, was included as a standard. Overall, in vitro activities of fleroxacin and norfloxacin were superposable, but interestingly, fleroxacin was two- to fourfold more active against Staphylococcus aureus, and 1 mg/l of fleroxacin inhibited all 5 multiply resistant Corynebacterium jeikeium tested. While both quinolones were similarly active weight by weight, fleroxacin with its more favorable pharmacokinetic properties harbors the added promise of clinical usefulness in systemic infections against susceptible isolates.

Effect of method, medium, pH and inoculum on the in-vitro antibacterial activities of fleroxacin and norfloxacin.

The comparative in-vitro activities of fleroxacin and norfloxacin were determined by standard agar dilution and broth micro-dilution methods in four different culture media, varying the pH of the medium (pH 5 to pH 8) and the inoculum size. Four inoculum densities equivalent to approximately 10(3), 10(4), 10(5) and 10(6) colony forming units per well or spot were prepared for each of five reference test strains (Escherichia coli ATCC 25922, E. coli ATCC 35218, Staphylococcus aureus ATCC 25923, S. aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853). The antibacterial activity of fleroxacin was similar overall to that of norfloxacin and rather uniform. The influence of the test conditions was moderate. However, the activity of both quinolones was uniformly lower at pH 5 in urine and against a high inoculum of 10(6) cfu/spot or well of S. aureus.

Fatal Legionella pneumophila pneumonia: treatment failure despite early sequential oral-parenteral amoxicillin-clavulanic acid therapy.

A 68-year-old male, having just returned from a two-week holiday on the Island of Ischia, developed unilateral pneumonia for which he was treated with oral amoxicillin-clavulanic acid and hospitalized within three days when the disease worsened and spread to both lungs. Despite parenteral amoxicillin-clavulanic acid (up to 2.2 g i.v. t.i.d.) the pneumonia spread rapidly over the next three days. Sputum cultures returned post mortem yielded Legionella pneumophila serogroup 1 and urine tests revealed the presence of Legionella antigen. Disk diffusion susceptibility testing on BCYE of the causative pathogen revealed zone diameters of inhibition of the clinical isolate exceeding 50 mm, indicating high susceptibility to this antibiotic combination. The therapeutic failure of amoxicillin-clavulanic acid should stimulate further reports and studies on the efficacy against legionellosis of this drug and similar beta-lactam inhibitor combinations as well as other beta-lactamase-stable beta-lactams.

Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study. Part II: Bacteriological results.

The in vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study. The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin. Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin against Streptococcus agalactiae. The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid. The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination against Neisseria meningitidis and Streptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations against Haemophilus influenzae type b.

Fleroxacin: in-vitro activity worldwide against 20,807 clinical isolates and comparison to ciprofloxacin and norfloxacin.

By June 1987 worldwide investigators from 37 centres in 12 countries had completed epidemiological susceptibility testing studies comparing the in-vitro activity of fleroxacin with that of ciprofloxacin, norfloxacin and other antibacterials. In this paper the results of these studies, expressed primarily as MIC90S, are reviewed and analysed for centre to centre variability. Twenty thousand eight hundred and seven strains were evaluable for comparative analysis. All three quinolones exhibited high in-vitro activity against Enterobacteriaceae (MIC90 less than or equal to 0.125-2 mg/l), other common aerobic Gram-negative bacilli or coccobacilli (MIC90 less than or equal to 0.125-1 mg/l) and staphylococci, including selected resistant isolates (MIC90 less than or equal to 0.5-4 mg/l), and moderate to weak activity against streptococci and anaerobes (MIC90 = 1- greater than or equal to 8 mg/l). The activity of fleroxacin and norfloxacin was quite similar, but was usually inferior to that of ciprofloxacin. Comparison of data from the various investigating centres showed divergent results for many bacterial species, the MIC90S for the same quinolone varying by two to four dilution steps or more from centre to centre.

Comparative in-vitro activity of fleroxacin and other 6-fluoroquinolones against mycobacteria.

The susceptibility of 11 clinical isolates of Mycobacterium tuberculosis, 3 M. kansasii, 3 M. xenopi, 2 M. scrofulaceum, 2 M. marinum, 2 M. malmoense to fleroxacin, ciprofloxacin, norfloxacin, rifampicin, isoniazid, ethambutol, and streptomycin was determined by the standard proportion method (Middlebrook 7H10 agar). All M. tuberculosis, M. kansasii, M. xenopi, M. scrofulaceum, M. marinum, and M, malmoense isolates including those resistant to conventional antimycobacterials were inhibited by 0.5 mg/l of fleroxacin and ciprofloxacin, the lowest tested concentration. Fleroxacin and ciprofloxacin along with ofloxacin, pefloxacin, ansamycin, clofazimine and cycloserine were also tested against 14 isolates of the M. avium complex. Nine of 14 strains (64%) of the M. avium complex were found susceptible to 4 mg/l of fleroxacin and a similar percentage to the other quinolones. On the basis of its in-vitro potency and its favourable pharmacokinetic properties fleroxacin appears to be sufficiently active to warrant further experimental trials against difficult to treat mycobacteria.

In vitro activity of carumonam (Ro 17-2301; AMA-1080) versus enteropathogenic and nonfermentative gram-negative rods and Legionella pneumophila.

The in vitro activity of carumonam (Ro 17-2301; AMA-1080) was tested against 355 single-patient isolates, by and large enteropathogenic or nonfermentative rods. The new monobactam was inhibitory and bactericidal against the majority of diarrhea-causing members of the family Enterobacteriaceae at concentrations of less than and equal to 8 micrograms/ml. Although known to be active against Pseudomonas aeruginosa, it generally did not exhibit clinically useful activity against other nonfermenters or against Legionella pneumophila, thus confirming its narrow spectrum of activity.

Cefetamet pivoxil: bacteriostatic and bactericidal activity of the free acid against 355 gram-negative rods.

The in vitro activity of the free acid of cefetamet pivoxil (Ro 15-8075) was tested against 355 clinical isolates, namely enteropathogenic bacteria, glucose non-fermentative gram-negative rods (excluding Pseudomonas aeruginosa) and Legionella pneumophila. Ceftriaxone was included in the study as reference compound. Although the free acid of the orally active cephalosporin was generally weaker than ceftriaxone, it inhibited 88.2% and 94.5% of Enterobacteriaceae and Vibrionaceae at a concentration of 4 mg/l and 8 mg/l or less, respectively. Campylobacter jejuni proved resistant to both compounds. The activity of the new compound against glucose non-fermentative gram-negative rods was generally insufficient to be of promise for broad clinical use. Although the compound was at least twofold more active than ceftriaxone against Pseudomonas acidovorans, Pseudomonas alcaligenes and Pseudomonas cepacia, the former was at least two dilution steps less active than the latter against 14 species of the other less common glucose non-fermentative organisms.

[Epidemiology of legionnaires' disease in Switzerland in 1988]. / Epidemiologie der Legionärskrankheit in der Schweiz im Jahre 1988.

Both sporadic cases and outbreaks of legionnaire's disease have been reported. To date, no outbreaks have occurred but several case reports have been published in Switzerland. The newly organized surveillance system of notifiable diseases, introduced in 1987, makes it possible for the first time to analyze reported sporadic cases more precisely. In 1988, the laboratories reported a total of 32 cases with cultural or serologic proof of legionellosis. In 75% of cases patients were aged over 40 years, 78% occurred among males. The majority of them were known to be smokers. In 9 cases an underlying predisposing condition was known: hairy cell leukemia (3 cases), immune hemolytic anemia (1), type 2 diabetes (2), chronic lung disease (1), heart failure (1). The case fatality was 9%. A possible source of exposure, such as air-conditioned rooms or evaporative condensers, was reported in 4 cases.

In vitro activities of Ro 40-6890 against 164 predominantly intestinal members of the families Enterobacteriaceae and Vibrionaceae.

The in vitro activities of Ro 40-6890, the active metabolite of a novel orally absorbable cephalosporin ester, Ro 41-3399, against 164 nonfastidious aerobic gram-negative rods of predominantly intestinal origin from patients with diarrhea were evaluated by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards. Ro 40-6890 was inhibitory (MIC for 90% of isolates [MIC90], 0.12 micrograms/ml) against the majority of intestinal members of the families Enterobacteriaceae and Vibrionaceae (Vibrio spp., Aeromonas spp., and Plesiomonas shigelloides). The potency of Ro 40-6890 was very similar to that of cefotaxime (MIC90, 0.12 micrograms/ml) and distinctly higher than those of cefadroxil (MIC90, > or = 128 micrograms/ml) and amoxicillin-clavulanic acid (MIC90, 32 micrograms/ml-2 micrograms/ml).

[Rubella epidemiology in military recruit schools]. / Rötelnepidemiologie in Rekrutenschulen.

In 1986, at the start of their training, 6877 male recruits were screened for the presence of anti-rubella IgG antibodies. 595 (9%) were seronegative. Of the latter group, 475 (80%) were retested in the week prior to discharge. During their four months of training, 113 (24%) exhibited seroconversion which proved acquisition of a rubella virus infection during the period of service. A clinical diagnosis of rubella was established in 15 (13%) of the persons with seroconversion. Catarrhal symptoms were present in half of those infected, whereas 41 (36%) did not report sick, suggesting a subclinical course of infection. Rubella is hardly a problem for the military in Switzerland. However, outbreaks such as the ones reported may have implications for the epidemiology of rubella in the general population, and hence should be taken into account in the planning of programs attempting to eliminate rubella virus infections.

Fleroxacin (Ro 23-6240): activity in vitro against 355 enteropathogenic and non-fermentative gram-negative bacilli and Legionella pneumophila.

The antibacterial activity of fleroxacin (Ro 23-6240, AM-833), a new 6-fluoroquinolone, was determined against 149 strains of enteropathogenic bacteria (17 species) and 191 strains (28 species) of glucose non-fermentative Gram-negative rods (excluding Pseudomonas aeruginosa), and against 15 strains of Legionella pneumophila. The cumulative susceptibility of these groups of bacteria to Ro 23-6240 at the 2 mg/l level were 99.2%, 80.1 and 100% of tested strains, respectively.

In vitro antibacterial properties of cefetamet and in vivo activity of its orally absorbable ester derivative, cefetamet pivoxil.

The in vitro activity of cefetamet, the microbiologically active metabolite of the orally administered prodrug cefetamet pivoxil, was compared with that of cephalexin, cefaclor, cefuroxime and amoxicillin. Cefetamet was highly active against Enterobacteriaceae, Neisseria spp., Vibrio spp., Haemophilus influenzae and streptococci other than enterococci. Cefetamet inhibited cefaclor-resistant species such as Proteus vulgaris, Providencia stuartii, Providencia rettgeri and Serratia marcescens. Staphylococci, Pseudomonas aeruginosa and cephalosporinase-overproducing strains of Enterobacter cloacae were resistant to cefetamet. The superior activity of cefetamet compared with older oral beta-lactam antibiotics against a large number of gram-negative pathogens correlated with enhanced stability towards beta-lactamases. In accordance with the in vitro findings, cefetamet pivoxil showed good activity in experimental infections in the mouse and rat, suggesting satisfactory bioavailability in these animals after oral administration.

In vitro activity of cefteram against predominantly enteropathogenic and glucose nonfermentative gram-negatives.

Cefteram (T-2525), the free acid of the orally active cephalosporin ester cefteram pivoxil, was tested in vitro against 355 gram-negative clinical isolates of enteropathogenic and nonfermentative species. The compound was several times more active (w/w) against isolates belonging to the enteropathogenic Enterobacteriaceae and Vibrionaceae than against those belonging to the nonfermentative rods (excluding Pseudomonas aeruginosa).