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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.

LB11058 is a new synthetic cephalosporin with good affinity for staphylococcal penicillin-binding protein 2a (PBP2a). LB11058 was tested in vitro and in rats with experimental aortic endocarditis against three methicillin-resistant Staphylococcus aureus (MRSA) strains, one penicillinase-negative strain (strain COL), and two penicillinase-producing strains (COL-Bla+ and P8-Hom). The MICs of LB11058 for the organisms were 1 mg/liter. The MICs of vancomycin and ceftriaxone were 1 and >/=64 mg/liter, respectively. In population analysis profiles, none of the MRSA strains grew at >/=2 mg of LB11058/liter. Rats with endocarditis were treated for 5 days. LB11058 was highly bound to serum proteins in rats (>/=98%). However, binding was saturable above a threshold of 250 mg/liter. Therefore, continuous concentrations of 250 mg/liter in serum were infused to ensure a free fraction (>/=5 mg/liter) above the drug's MIC for the entire infusion period. Control treatments included simulation of human serum kinetics produced by intravenous vancomycin (1 g twice daily, free drug concentration above MIC, >/=90% of infusion period) or ceftriaxone (2 g/24 h, free drug concentrations above the MIC, 0% of infusion period). LB11058 successfully treated 10 of 10 (100%) and 13 of 14 (93%) of rats infected with COL-Bla+ and P8-Hom, respectively. This was comparable to vancomycin (sterilization of 8 of 12 [66%] and 6 of 8 [75%] rats, respectively). Ceftriaxone was inactive. Low concentrations of LB11058 (5 and 10 mg/liter, continuously infused) in serum were ineffective, as predicted by the pharmacodynamic parameters. At appropriate doses, LB11058 was highly effective both in vitro and in vivo. This finding supports the development of this beta-lactam with high PBP2a affinity for the treatment of MRSA infections.

Purpose: To evaluate the clinical relevance of cephalosporin (ceftriaxone/cefotaxime) resistance among patients with nonmeningeal systemic pneumococcal infection., Subjects and Methods: From January 1994 to October 2000, we prospectively studied 522 episodes of nonmeningeal systemic pneumococcal infections (448 pneumonias) in 499 adults who were treated according to hospital guidelines. In vitro antibiotic susceptibility, as the minimum inhibitory concentration (MIC), was determined by microdilution method. The MIC methods and breakpoints (cutoffs) were established by the National Committee for Clinical Laboratory Standards., Results: Of the 522 pneumococcal strains, 413 strains (79%) were susceptible to ceftriaxone/cefotaxime, MIC < or =0.5 microg/mL; 79 (15%) were intermediate, MIC = 1 microg/mL; and 30 (6%) were resistant, MIC = 2 microg/mL. After adjusting for several variables, including pneumococcal serogroups/serotypes, infections due to nonsusceptible (intermediate and resistant) pneumococcal strains were independently associated with prior antibiotic therapy, with an odds ratio of 5.9 (95% confidence interval: 2.6 to 13.6). Thirty-day mortality among the 185 patients who were treated with ceftriaxone (1 g/d) or cefotaxime (1.5 g every 8 hours) did not differ by cephalosporin susceptibility: 18% (26/148) among those with susceptible organisms, 13% (3/24) with intermediate organisms, and 15% (2/13) in resistant cases (P = 0.81)., Conclusion: Ceftriaxone or cefotaxime were effective in treating patients with nonmeningeal systemic pneumococcal infections caused by strains with MIC < or =2 microg/mL. These results support the newly established ceftriaxone/cefotaxime MIC breakpoints (cutoffs) for nonmeningeal pneumococcal infections.

The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant Staphylococcus aureus (MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant S. aureus strain COL transformed with the penicillinase-encoding plasmid pI524 (COL Bla+) and homogeneously methicillin-resistant, penicillinase-producing isolate P8-Hom, selected by serial exposure of parent strain P8 to methicillin. The MICs of BAL9141 for these organisms (2 mg/liter) were low, and BAL9141was bactericidal in time-kill curve studies after 24 h of exposure to either two, four, or eight times the MIC. Rats with experimental endocarditis were treated in a three-arm study with a continuous infusion of BAL5788 (formerly Ro 65-5788), a carbamate prodrug of BAL9141, or with amoxicillin-clavulanate or vancomycin. The rats were administered BAL9141 to obtain steady-state target levels of 20, 10, and 5 mg of per liter or were administered either 1.2 g of amoxicillin-clavulanate (ratio 5:1) every 6 h or 1 g of vancomycin every 12 h at changing flow rates to simulate the pharmacokinetics produced in humans by intermittent intravenous treatment. Treatment was started 12 h after bacterial challenge and lasted for 3 days. BAL9141 was successful in the treatment of experimental endocarditis due to either MRSA isolate COL Bla+ or MRSA isolate P8-Hom at the three targeted steady-state concentrations and sterilized >90% of cardiac vegetations (P < 0.005 versus controls; P < 0.05 versus amoxicillin-clavulanate and vancomycin treatment groups). These promising in vivo results with BAL9141 correlated with the high affinity of the drug for PBP 2a and its stability to penicillinase hydrolysis observed in vitro.

Ro 63-9141 is a new member of the pyrrolidinone-3-ylidenemethyl cephem series of cephalosporins. Its antibacterial spectrum was evaluated against significant gram-positive and gram-negative pathogens in comparison with those of reference drugs, including cefotaxime, cefepime, meropenem, and ciprofloxacin. Ro 63-9141 showed high antibacterial in vitro activity against gram-positive bacteria except ampicillin-resistant enterococci, particularly vancomycin-resistant strains of Enterococcus faecium. Its MIC at which 90% of the isolates tested were inhibited (MIC(90)) for methicillin-resistant Staphylococcus aureus (MRSA) was 4 microg/ml. Ro 63-9141 was bactericidal against MRSA. Development of resistance to the new compound in MRSA was not observed. Ro 63-9141 was more potent than cefotaxime against penicillin-resistant Streptococcus pneumoniae (MIC(90) = 2 microg/ml). It was active against ceftazidime-susceptible strains of Pseudomonas aeruginosa and against Enterobacteriaceae except Proteus vulgaris and some isolates producing extended-spectrum beta-lactamases. The basis for the antibacterial spectrum of Ro 63-9141 lies in its affinity to essential penicillin-binding proteins, including PBP 2' of MRSA, and its stability towards beta-lactamases. The in vivo findings were in accordance with the in vitro susceptibilities of the pathogens. These data suggest the potential utility of Ro 63-9141 for the therapy of infections caused by susceptible pathogens, including MRSA. Since insufficient solubility of Ro 63-9141 itself precludes parenteral administration in humans, a water-soluble prodrug, Ro 65-5788, is considered for development.

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.

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)

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).

Ro 41-3399 is a novel orally active ester of Ro 40-6890, an aminothiazolyl cephalosporin with potent in vitro activities against commonly encountered aerobic gram-positive bacteria (streptococci and methicillin-susceptible staphylococci) and gram-negative bacteria (members of the family Enterobacteriaceae, haemophili, meningococci, and gonococci). In terms of the MICs determined by the methods recommended by the National Committee for Clinical Laboratory Standards, for 50 and 90% of gram-positive organisms, the water-soluble free carboxylic acid Ro 40-6890 proved to be at least as active as or two- to fourfold more active than cefpodoxime, cefuroxime, cefaclor, amoxicillin, amoxicillin-clavulanic acid, and ceftriaxone; against aerobic gram-negative organisms, Ro 40-6890 was usually two- to fourfold more active than cefpodoxime, the next most potent of the oral drugs under comparison, but remained usually two- to fourfold weaker than ceftriaxone. Ro 40-6890 showed a high affinity for the essential penicillin-binding proteins of susceptible bacteria and was resistant to hydrolysis by a broad array of beta-lactamases. Ro 41-3399 bopentil was well absorbed in mice when administered by oral gavage and proved effective in several experimental bacterial infections. Further studies with Ro 41-3399 and Ro 40-6890 are in progress.

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.

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.

The detection of travel-associated legionellosis can be extremely difficult; hence, an extensive case investigation is recommended in pneumonia-striken travellers and tourists, who are particularly at risk of acquiring the disease. On the Island of Ischia (Isola d'Ischia, Naples, Italy) a total of six cases of Legionnaires' disease occurred from 1986 to 1990. All patients (one man and two women from Germany, one Austrian woman, one Swiss man, and one Italian woman) had taken thermal baths and stayed in local hotels; they all experienced severe pneumonia, and three of them died. These cases were associated with hotels, and the hot-water supply was presumed to have transmitted the infection. Remedial procedures were applied to the hot-water plumbing of the hotels according to the WHO recommendations and were proved to be effective. The occurrences described in this paper stress the importance of rapid and accurate reporting of diagnosed cases to the country where the infection was probably acquired, in order to ensure early detection of endemic foci and emerging clusters of legionellosis.

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.

Fleroxacin and cefetamet were evaluated in vitro against 38 infrequently encountered species (250 strains) of the family Enterobacteriaceae and compared with four established compounds. For all the strains tested, the fleroxacin MIC was less than or equal to 0.5 mg/liter, and for 98% of strains the cefetamet MIC was less than or equal to 8 mg/liter; even though the two new compounds did not quite reach the activities (on a weight-by-weight basis) of ciprofloxacin and ceftriaxone, respectively, they nonetheless clearly surpassed trimethoprim-sulfamethaxazole and amoxicillin-clavulanic acid. The very potent new oral compounds tested in this study appear to be promising for the treatment of clinically relevant infections due to uncommon species of Enterobacteriaceae.

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.

In a prospective Swiss multicenter study, 119 children (aged three weeks to 15.5 years) with acute bacterial meningitis were treated with single daily doses of ceftriaxone (100 mg/kg on days one and two and 60 mg/kg thereafter). All patients were randomly assigned to either short course (four, six, seven days) or full course (eight, 12, 14 days) therapy depending on whether they had contracted meningococcal, Haemophilus influenzae type b or pneumococcal meningitis. Bacteriological cure was obtained in 92 children who fully completed the study and in all the 20 culture-positive of the 27 children secondarily excluded from the study for failure to meet all bacteriological and initial safety criteria for continuation in protocol (secondary exclusions). Complete clinical recovery was noted in 105 of 119 patients (88%) and was as frequent in the short course (91%) as in the full course (89%), and as in the secondary exclusion (81%) group. All patients survived. At follow-up examination three to six months after hospital discharge only seven infants and seven children (11.8%), mostly those with poor presentation on admission (p = 0.0012), showed residual neurological sequelae. Side effects of antibiotic therapy were minor but more frequent, albeit not statistically significant (p = 0.065), in children receiving the full course therapy. The results of this study suggest that short course treatment of acute bacterial meningitis in children with single daily ceftriaxone monotherapy is as efficacious as full course therapy and at least as well tolerated.

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.

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).

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.

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.

Wangiella dermatitidis, a normally saprophytic dematiaceous fungus, has rarely been reported as a cause of disease in humans. A review of the worldwide literature yielded eight validly documented cases of W. dermatitidis infections. Reported herein is a subcutaneous knee infection due to W. dermatitidis in a diabetic man with impaired T-cell function and cutaneous anergy. Repeated cultures of the lesion were positive for W. dermatitidis despite therapy with amphotericin B. It is believed that this represents the first well-documented case of infection due to W. dermatitidis in North America, although the fungus has previously been isolated from nature in several states. The current state of knowledge of this organism, based on previously reported cases and isolations from nature, are discussed. No curative medical therapy is known for this infection, but surgical excision seems to be the treatment of choice for circumscribed W. dermatitidis infections.

We report a case of asphyxia due to laryngeal obstruction by an esophageal polyp with subsequent cerebral anoxia and death. We review the clinical manifestations and pathological aspects of benign esophageal tumors, with emphasis on the importance of an early diagnosis if a patient has repeated sensations of a regurgitated pharyngeal mass.

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.

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.

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.

The circumstances, clinical symptoms, and outcome of a case of human rabies are reported. The disease was conveyed by a housecat. Since the report gave no cause for concern, antirabies vaccination was not considered to be necessary. After a delay of 157 days prodromi appeared and the patient was finally hospitalized 3 days later displaying signs of the encephalitic stage. After 2 days, the patient went into the paralytic stage; death occurred 3 days later due to refractory circulatory and respiratory failure. In endemic rabies areas such as Switzerland, human rabies may, as demonstrated by our case report, always sporadically occur. Rabies should be considered in cases of encephalitis or encephalitis-like syndromes.

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.

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.

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.