Dealing with waterborne disease in Canada: challenges in the delivery of safe drinking water.

Protecting the public from waterborne diseases is an environmental health responsibility that every government worldwide must deal with. Canada's recent experience with waterborne outbreaks has brought the effectiveness of its water-monitoring and treatment systems under scrutiny. This paper focuses on microbial waterborne diseases and the shortcomings of drinking-water systems, dividing them into source control, monitoring, treatment, and operation, epidemiologic, and risk communication issues. Whereas some of these issues are often addressed, others, such as risk communication issues, are less frequently included in drinking water-management plans. Lessons can be learned from the Canadian experience, as these issues are applicable worldwide and especially in the developed world.

Methanol exposure to car occupants from windshield washing fluid: a pilot study.

UNLABELLED: Automobile occupants might be exposed to considerable amounts of methanol from previously unreported source, namely via the inhalation of vapors of winter-grade, methanol-based, windshield washing fluid that drains to the intake air ducts of the car. Air samples were collected in passenger cars during simulated operating conditions and analyzed for methanol via headspace gas chromatography-mass spectrometry, electron impact, selected ion monitoring. The method was linear in the 2-2000 ppm range. Concentrations exceeding 1000 ppm were recorded. PRACTICAL IMPLICATIONS: Using a winter-grade, methanol-based, windshield washing fluid for windshield cleaning in a passenger car can result in a methanol concentration in the air of the passenger cabin in excess of 1000 ppm. In view of the widespread use of this product, more studies are necessary to elucidate, in depth, the concentrations of methanol vapors which could be encountered in various weather and driving conditions as well as the concomitant contributing influences of car design. These studies are necessary to properly assess the hazards associated with use of the fluid and possible mitigation approaches which might include substitution of methanol by less toxic formulations.

Sub-clinical infection and asymptomatic carriage of Cryptococcus gattii in dogs and cats during an outbreak of cryptococcosis.

Since 1999, Cryptococcus gattii has emerged as an important pathogen of humans and animals in British Columbia, Canada. Nasal swabs and serum samples were collected from dogs and cats residing within the Coastal Douglas Fir biogeoclimatic zone on Vancouver Island, where clinical cases have been reported. Deep and superficial nasal fungal cultures of 280 dogs and 94 cats identified four (4.3%) cats and three (1.1%) dogs with C. gattii serotype B in their nasal cavity. Serum samples collected from 266 dogs and 84 cats identified six (7.1%) cats and two (0.8%) dogs with a positive cryptococcal antigen titer. Overall cats were 4.4 times more likely than dogs to be positive on one or both tests. Identification of sub-clinical infection and nasal colonization is an important step in the characterization of the outbreak of clinical cryptococcosis on Vancouver Island.

Follow-up study of dogs and cats with asymptomatic Cryptococcus gattii infection or nasal colonization.

The pathogenesis of Cryptococcus spp. infection following nasal colonization is unclear. This article reports follow-up data on a cohort of seven cats and five dogs identified in a previous study as sub-clinically infected with Cryptococcus spp. or colonized by C. gattii. Two cats progressed to clinical disease within four to six months of initial detection of antigenemia and nasal cavity colonization. The ten other animals remained asymptomatic but many were repeatedly positive on cryptococcal antigen testing or nasal fungal culture suggesting protracted infection or colonization. The results indicate that asymptomatically infected animals may clear the organism, remain sub-clinically infected or progress to clinical disease. Factors influencing the transition from exposure to disease require further investigation.

A rare genotype of Cryptococcus gattii caused the cryptococcosis outbreak on Vancouver Island (British Columbia, Canada).

Cryptococcus gattii causes life-threatening infection of the pulmonary and central nervous systems in hosts with normal immunity and traditionally has been considered to be restricted geographically to tropical and subtropical climates. The recent outbreak of C. gattii in the temperate climate of Vancouver Island, BC, Canada, led to a collaborative investigation. The objectives of the current study were to ascertain the environmental source of the outbreak infections, survey the molecular types of the outbreak and environmental cryptococcal isolates, and determine the extent of genetic diversity among the isolates. PCR-fingerprinting and amplified fragment length polymorphism (AFLP) were used to examine the genotypes, and mating assays were performed to determine the mating type of the isolates. All outbreak and environmental isolates belonged to C. gattii. Concordant results were obtained by using PCR-fingerprinting and AFLP analysis. The vast majority of clinical and veterinary infections were caused by isolates of the molecular type VGII/AFLP6, but two were caused by molecular type VGI/AFLP4. All environmental isolates belonged to molecular type VGII/AFLP6. Two or three subtypes were observed within VGII/AFLP6 among outbreak and environmental isolates. All mating-competent isolates were of the alpha-mating type. The emergence of this usually tropical pathogen on Vancouver Island highlights the changing distribution of this genotype and emphasizes the importance of an ongoing collaborative effort to monitor the global epidemiology of this yeast.

A field comparison of four samplers for enumerating fungal aerosols I. Sampling characteristics.

UNLABELLED: This study compared the performance of four bioaerosol samplers, the Reuter Centrifugal Air Sampler, the Andersen N6 single stage, the Surface Air System 90, and the Air-o-Cell, in measurements for airborne fungal propagules collected in 75 public building sites without prior knowledge of water damage or mold problems in British Columbia, Canada. The samplers had differences in detection limits, reproducibility, and overall yield. However, high and significant correlations between samplers (indoor samples: Pearson r = 0.60-0.85, P < 0.001) suggest that relative performances between samplers were reasonably consistent. These results indicate that fungal airborne concentration data are dependent on the methods used for assessment, and introduce additional variability in exposure assessment studies. PRACTICAL IMPLICATIONS: In the absence of a standard protocol for sampling bioaerosols, the interpretation of aerosol data reported in indoor air quality studies is entirely dependent on an appreciation of the sampling characteristics of commonly used instrumentation. Although a number of comparative studies have been undertaken in the laboratory, only a few studies have made reported comparison data under field conditions. This study compared three culturable sampling devices, the Andersen N6, SAS 90, and RCS, and one particulate sampling device, the Air-o-Cell, in offices and public areas in a variety of buildings, under conditions of forced air or natural ventilation. The concentrations of fungal aerosols collected during simultaneous sample collection were highly correlated, yet varied by orders of magnitude. The performance of these devices must be carefully considered before a standard protocol can be promulgated.

A field comparison of four fungal aerosol sampling instruments: inter-sampler calibrations and caveats.

UNLABELLED: Four bioaerosol samplers (Reuter Centrifugal, Andersen N6 Single Stage, Surface Air System Super 90, and Air-o-Cell) were used to take c. 300 side-by-side measurements at 75 public building sites. Regression models were developed to examine the relationships between each method pair. The models demonstrate that measurements from these instruments are not directly comparable, requiring inter-instrument calibration. Sampling location (indoor vs. outdoor) was a confounder in all the pairwise comparisons between samplers. In addition, the slopes of the relationships between all method pairs except one differed in indoor vs. outdoor locations. These results emphasize that direct comparisons between methods should not be undergone without prior calibration. Where measurement circumstances are similar to those of this study, the regression models might serve as a basis to convert measurements made with one instrument to those made with another. However, the robustness and generalizability of the models in different measurement settings needs to be assessed. PRACTICAL IMPLICATIONS: Many different bioaerosol sampling devices are in common use for indoor air quality studies. If data from research studies are to be compared, an approximation of the relationships between the equipment would be useful. A comparison of three culturable sampling devices (Andersen N6, SAS 90, RCS) and one particulate sampling device (Air-o-Cell) collecting simultaneous samples under field conditions showed high linear correlations between methods. However, while direct comparisons between sampling data were not possible, the regression models reported here explained 60-85% of the variance in fungal concentrations, and underscored the importance of the effect of environment on measurement.

Point-of-sale glass bottle recycling: indoor airborne exposures and symptoms among employees.

AIMS: To assess the impact of newly introduced point-of-sale glass bottle recycling on indoor air quality and employee health. METHODS: Airborne exposures and both chronic and acute respiratory and somatic symptoms were surveyed among 226 employees at 36 randomly selected liquor stores with bottle recycling and in-house glass breaking. Each store was visited twice; between visits glass breaking was discontinued for one month in half the stores (selected at random), although bottles were still collected and stored on site. Rates of chronic symptoms were compared to an external, unexposed control population. RESULTS: Geometric mean exposure levels were 0.18 mg/m3 for inhalable particulate matter and 3.6 EU/m3 for endotoxin (270 personal samples); 1064 CFU/m3 for viable fungi (648 area samples). Fungal levels were associated with visibly mouldy bottles being broken, outdoor fungal counts, and uncovered glass bins. Exposures were not altered by the intervention of shutting down glass breaking machinery. Compared to controls, employees reported more work related chronic chest tightness and chronic nasal symptoms. Acute chest symptoms were associated with breaking visibly mouldy bottles, but not with measured fungal counts. Inhalable particulate matter levels >0.2 mg/m3 were associated with acute upper airway irritation. Somatic symptoms were associated with measures of psychosocial job strain. CONCLUSION: Results suggest that this type of recycling programme may generate fungal exposures sufficient to elicit upper airway and chest symptoms.

Application of a modified bioassay for monitoring serum teicoplanin and vancomycin in febrile neutropenic patients.

Teicoplanin is a glycopeptide antibiotic with a mode of action and spectrum of activity similar to those of vancomycin. Its efficacy and tolerability as empiric therapy and its pharmacokinetic properties in neutropenic patients are being studied in a double-blinded, randomized trial in comparison with those of vancomycin. We report here a modified agar diffusion bioassay which is suitable for monitoring levels of either teicoplanin or vancomycin in serum during combination therapy with beta-lactams, aminoglycosides, and amphotericin B. Serum samples spiked with either teicoplanin or vancomycin gave reproducible results (mean coefficient of variation, 8.8%) regardless of the presence of tobramycin, amikacin, piperacillin, ceftazidime, amphotericin B, or their combinations. Among 25 patients who received teicoplanin at a dosing schedule of 6 mg/kg every 24 h intravenously, steady state was reached after 14.2 +/- 4.0 days, and 1-h peak and trough concentrations of teicoplanin in serum at steady state were 40.8 +/- 15.0 and 12.5 +/- 3.2 mg/liter, respectively. In contrast, among 25 patients who received vancomycin at a dosing schedule of 15 mg/kg every 12 h intravenously, steady state was reached by 24 h, and the 1-h peak and trough concentrations in serum were 37.5 +/- 15.6 and 8.3 +/- 3.8 mg/liter, respectively. The elimination half-lives for teicoplanin estimated by two separate approaches agreed closely with each other: 80.5 +/- 21.5 h by an accumulation model (M. Gilbaldi and D. Perrier, Pharmacokinetics, 2nd ed., p. 121, 1982) and 87.3 +/- 19.3 h as predicted from the degree of renal function (M. Rowland, Clin. Pharmacokinetic 18:184-209, 1990). These values were 14- to 15-fold higher than that for vancomycin (5.6 +/- 1.8 h). Since considerable variability was noted in the pharmacokinetic parameters for both teicoplanin and vancomycin among the individual patients, our data further emphasized the need for frequent monitoring of these drugs during empiric therapy of the febrile neutropenic patient.

Colony immunoblot assay for the detection of staphylococcal toxic shock syndrome toxin 1 (TSST-1) with anti-TSST-1 F(ab')2 fragments.

Toxic shock syndrome toxin 1 (TSST-1), an exoprotein of Staphylococcus aureus, is strongly implicated in the pathogenesis of TSS. Detection of TSST-1, however, is often hindered in immunoassays because of the cosecretion of protein A, a genetic trait which appears to be coordinately expressed with other exoproteins in S. aureus. We developed a colony immunoblot assay for rapid screening of TSST-1-producing S. aureus using TSST-1-specific rabbit F(ab')2 fragments. The sensitivity and specificity of this method were compared with those of a quantitative noncompetitive enzyme-linked immunosorbent assay (ELISA) for 34 S. aureus isolates (17 TSS-associated and 17 non-TSS-associated isolates). Cosecreted protein A in culture supernatants was evaluated by a quantitative competitive ELISA. The results clearly indicated the superiority of F(ab')2 fragments in eliminating nonspecific reactivity of protein A in the colony immunoblot assay. The sensitivity of the immunoblot with TSST-1-specific F(ab')2 was similar to that with whole immunoglobulin G (94 versus 82%, respectively; P = 0.601, Fisher's exact test), but the specificity was markedly improved (94 versus 59%, respectively; P = 0.039). Among TSST-1-negative isolates (as determined by ELISA), strains which gave false-positive results in the immunoglobulin G immunoblot assay produced higher amounts of protein A than strains which gave true-negative results (P = 0.08, Mann-Whitney rank sum test, one tailed). Among strains positive for TSST-1, the level of TSST-1 detected in culture supernatants correlated inversely with the amount of protein A secreted (rs = -0.64; P less than 0.01, Spearman rank correlation). These findings validate the utility of a rapid screening method for the detection of TSST-1-producing S. aureus and support the concept of coordinate secretion of exoproteins in S. aureus.

Cross-resistance of Pseudomonas aeruginosa to ciprofloxacin, extended-spectrum beta-lactams, and aminoglycosides and susceptibility to antibiotic combinations.

The susceptibilities of 270 clinical isolates of Pseudomonas aeruginosa from diverse sources (82 burn patients, 76 cystic fibrosis [CF] patients, and 112 other sources) to ciprofloxacin and three other quinolones, nine extended-spectrum beta-lactams, and three aminoglycosides were determined by an agar dilution method in cation-supplemented Mueller-Hinton medium. Ciprofloxacin, ceftazidime, imipenem, and aztreonam were the most active. MICs for burn isolates were consistently higher than those for other isolates for most antibiotics, whereas those for CF strains were consistently lower. Multidrug resistance to aminoglycosides and beta-lactams occurred in 21% of the burn isolates, 2.6% of the CF isolates, and 8.9% of the other isolates. Ninety percent of these strains remained susceptible to ciprofloxacin. Seven percent of the isolates were resistant to ciprofloxacin (MIC, greater than or equal to 2 micrograms/ml). Concurrent resistance to ciprofloxacin and beta-lactams or aminoglycosides was rare (1.8 to 4%). Analysis by Spearman rank correlation revealed a high degree of correlation of MICs among antibiotics within the same class, except for imipenem. An inoculum effect was observed for all antibiotics between 10(6) and 10(4) CFU (P less than 0.05), with those for piperacillin and cefoperazone being the most pronounced (16-fold and 8-fold differences, respectively), and was least apparent for the quinolones, aminoglycosides, imipenem, and aztreonam (twofold differences). Selected strains for which there were high MICs of ciprofloxacin (greater than or equal to 1 micrograms/ml) were tested against ciprofloxacin in combination with other agents in a checkerboard agar dilution assay. Synergistic (summated fractional inhibitory concentration, /= 4) was observed in only one instance (with gentamicin).

Purification and purity assessment of toxic shock syndrome toxin 1.

Toxic shock syndrome toxin 1 (TSST-1) was partially purified from culture supernatants by SP-Sephadex C-25 ion-exchange chromatography and subsequent Sephadex G-75 gel filtration. This protein had an apparent molecular weight of 24,000 and an isoelectric point of 7.0. The NH2-amino acid sequence for the first 40 residues agreed completely with that predicted from the known TSST-1 genome. Ouchterlony immunodiffusion with monospecific rabbit antisera demonstrated a single line of identity with reference TSST-1 as well as with three preparations obtained from other investigators. When the purity of the different TSST-1 preparations was examined by Coomassie blue or silver staining after SDS-PAGE, only the major band at molecular weight 24,000 was apparent. However, multiple additional bands were seen in all preparations when visualized either by double staining with Coomassie blue stain followed by silver stain or by immunoblot using pooled human serum. Further purification of our preparation by reverse-phase high-performance liquid chromatography eliminated some, but not all, extraneous antigens. A final purification step by preparative SDS-PAGE resulted in an eluted protein that yielded only the 24-kDa TSST-1 band and a 48-kDa dimer by immunoblot. This material was endotoxin free (sensitivity limit, 10 pg/mL) and retained biologic activity for induction of cachectin and production of interleukin 1 by human monocytes. These data emphasize the need for stringent methods of assessment of purity in TSST-1 preparations.

Sequential assessment of vaginal microflora in healthy women randomly assigned to tampon or napkin use.

The effect of tampon usage on the vaginal microflora of 35 healthy women was determined following their random allocation to either tampon or napkin use for three consecutive menstrual cycles. Sequential and semiquantitative vaginal cultures were obtained on days 3 +/- 2, 15 +/- 2, and 25 +/- 2 of the menstrual cycle (day 1, first day of menses) before and after randomization. Before randomization, the rate of isolation and median counts of facultative lactobacilli were significantly higher (P less than .05) and that of eubacteria was significantly lower (P = .026) among regular tampon users than among exclusive napkin users. After randomization, only median counts of coagulase-negative staphylococci were significantly increased (P = .025) during tampon use compared with the rates for the same women during napkin use. These shifts in vaginal microflora occurred only in samples obtained during menstruation and not in those obtained at other sampling times. The data presented here support the notion that the use of tampons may result in alterations in the autochthonous vaginal microflora. It remains to be determined if these ecologic shifts in the vaginal microflora may adversely affect resistance to colonization by potential pathogens in the lower female genital tract.

Serologic responses to toxic shock syndrome (TSS) toxin-1 in menstrual and nonmenstrual TSS.

Toxic shock syndrome toxin-1 (TSST-1) is implicated as the major exotoxin associated with menstrual toxic shock syndrome. The role of TSST-1 in nonmenstrual TSS is less certain. We examined serum IgG responses to TSST-1 in 16 nonmenstrual (9 female, 7 male) and 14 menstrual TSS patients, and in 87 women and 66 men as age-matched healthy controls, using an enzyme-linked immunosorbent assay (ELISA). Relative ELISA titers were expressed as percent activity of a mid level serum standard tested concurrently. Based on 95% confidence estimates for predicting a negative titer (20.6 +/- 8.2%) using sera in which TSST-1 specific IgG was demonstrated to be absent by western blot, 24% of control women and 9% of control men lacked TSST-1 specific IgG in the random survey (p less than 0.05, Fisher's exact test). Relative titers in acute sera of menstrual TSS women (26.2 +/- 5.2%, mean +/- S.E.), but not nonmenstrual TSS women (71.8 +/- 18.6%), were significantly lower than those of control women (78.9 +/- 7.3%, p less than 0.01, Mann-Whitney test). Acute titers from male TSS patients (37.0 +/- 15.6%) were also significantly lower than those in control men (114.6 +/- 11.0% (p less than 0.05). Antibody titers from menstrual TSS women and TSS men remained low during convalescence. Nevertheless, seroconversion to TSST-1 was demonstrated by western blot in 7 of 10 patients in whom TSST-1 positive S. aureus was isolated, but in neither of two patients without toxigenic S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)

Synergistic interactions of ciprofloxacin and extended-spectrum beta-lactams or aminoglycosides against multiply drug-resistant Pseudomonas maltophilia.

The susceptibility of 28 clinical isolates of Pseudomonas maltophilia to 16 antimicrobial agents was determined in vitro by a standard agar dilution method with inoculum sizes of 10(4) and 10(6) CFU. All isolates exhibited multiple drug resistance. Nine isolates were selected for studies of combinations of ciprofloxacin with seven antipseudomonal beta-lactams and three aminoglycosides by a checkerboard agar dilution technique. Synergistic or additive combinations of ciprofloxacin in clinically achievable concentrations were most frequent with mezlocillin (89%), followed by cefoperazone (67%), piperacillin (56%), cefsulodin (56%), and ceftazidime (33%), and were infrequent with aztreonam (11%), the aminoglycosides (0 to 14%), or imipenem (0%). Antagonism was not observed in any combination. These data suggest that combinations of ciprofloxacin with these agents may be useful for some nosocomial multiply drug-resistant P. maltophilia infections.

Synergistic interactions of ciprofloxacin and extended spectrum beta-lactams or aminoglycosides against Acinetobacter calcoaceticus ss. anitratus.

The susceptibility of 54 clinical isolates of Acinetobacter calcoaceticus ss. anitratus to 16 antimicrobial agents was determined in vitro with inoculum of 10(4) and 10(6) cfu by a standard agar dilution method. The most active agents were imipenem, SCH 34343, ciprofloxacin, difloxacin (A-56619), and A-56620. Only imipenem and Abbott quinolones (A-56619 and A-56620) remained active when tested with the heavier inoculum. Except for ticarcillin and ceftazidime, which showed only moderate activity, the extended-spectrum penicillins and cephalosporins, as well as aztreonam and aminoglycosides, were inactive against these highly resistant strains. Nine isolates were selected for combination studies of ciprofloxacin with seven beta-lactams and three aminoglycosides using a checkerboard agar dilution technique. Synergistic or additive interactions at clinically achievable concentrations were more common with amikacin (eight isolates), tobramycin (seven), ceftazidime (six), cefoperazone (six), and aztreonam (six), than with other agents, including mezlocillin (four), piperacillin (three), gentamicin (two), and cefsulodin (two). Antagonism was rare, only occurring with mezlocillin in a single strain. These data suggest that combinations of ciprofloxacin with these agents may be useful for some nosocomial multidrug resistant A. calcoaceticus ss. anitratus infections.

Detection and quantitation of toxic shock syndrome toxin 1 in vitro and in vivo by noncompetitive enzyme-linked immunosorbent assay.

Toxic shock syndrome toxin 1 (TSST-1), an exotoxin produced by many Staphylococcus aureus strains, is implicated as the prime causal agent of toxic shock syndrome (TSS). A sensitive and specific noncompetitive enzyme-linked immunosorbent assay (ELISA) capable of detecting TSST-1 at concentrations from 0.5 to 16 ng/ml was developed. This assay did not detect other staphylococcal enterotoxins including A, B, C1, C2, C3, D, and E. Possible interactions with protein A were readily eliminated by pretreatment of test samples with 10% normal rabbit serum. The assay was adapted for rapid screening of TSST-1 production by S. aureus isolates in culture supernatants in vitro and for detection of TSST-1 in vaginal washings of TSS patients and healthy controls in vivo. All 35 S. aureus isolates confirmed to be TSST positive by Ouchterlony immunodiffusion and 59 of 60 isolates confirmed to be TSST-1 negative gave concordant results by ELISA. Interestingly, toxigenic S. aureus strains isolated from TSS patients quantitatively produced significantly more TSST-1 in vitro compared with toxigenic control strains (P less than 0.05, Mann-Whitney rank sum test). TSST-1 could be detected by ELISA in three of four vaginal washings collected within 3 days of hospitalization from three women with acute menstrual TSS, compared with 0 of 17 washings from nine TSS patients hospitalized longer than 3 days (P = 0.003, Fisher's exact test) and 1 of 15 washings from 14 healthy control women (P = 0.016). This noncompetitive ELISA should be particularly useful for rapid screening of TSST-1 production by S. aureus isolates, for the purification and biochemical characterization of TSST-1, and for human and animal studies of the pathogenesis of TSS.

Comparison of susceptibility of gentamicin-resistant and -susceptible "Acinetobacter anitratus" to 15 alternative antibiotics.

Fifty-four clinical isolates of "Acinetobacter anitratus" separated cleanly into gentamicin-susceptible (16 strains) and gentamicin-resistant (38 strains) subpopulations. When tested with a 10(4)-CFU inoculum, gentamicin resistance was associated with a greater than fourfold increase in the MICs of norfloxacin, ciprofloxacin, A-56620, tobramycin, and amikacin for 50% of the strains. Antimicrobial agents with MICs for 90% of gentamicin-resistant strains in the susceptible range were ciprofloxacin, A-56619, A-56620, imipenem, SCH-34343, ceftazidime, aztreonam, carbenicillin, ticarcillin, and piperacillin. These agents may be useful alternative drugs for treating infections caused by aminoglycoside-susceptible and -resistant "A. anitratus."

Vaginal colonization with Escherichia coli in healthy women. Determination of relative risks by quantitative culture and multivariate statistical analysis.

The rate of vaginal colonization with Escherichia coli in 495 healthy women was 12% in a prospective study with use of selective media and semiquantitative culture techniques. Computer-assisted multivariate analysis revealed that vaginal E. coli was significantly associated with the menstrual phase of the cycle, prior use of antibiotics, use of diaphragm or cervical cap for contraception, history of previous urinary tract infection, and coisolation of Staphylococcus aureus that was positive for the toxic shock syndrome toxin-1 (p less than 0.05, multiple stepwise logistic regression analysis). No significant association was observed with tampon use or brand, other contraceptive methods, sexual activity, genital symptoms, recent vaginal infection, or other personal habits. Quantitative cultures obtained sequentially throughout the menstrual cycle in 12 unselected women confirmed higher E. coli counts in menstrual or midcycle samples compared to paired premenstrual specimens (p less than 0.05, Wilcoxon paired rank sign test). These data emphasize the hormonal and other host determinants in vaginal colonization by E. coli and may explain the high rate of vaginal E. coli (64%), in addition to toxicogenic S. aureus, in acute toxic shock syndrome and the higher incidence of urinary tract infection in women with diaphragm or cervical cap for contraception compared to other contraceptive methods.

In vitro susceptibility of Clostridium difficile to new beta-lactam and quinolone antibiotics.

The in vitro susceptibilities of 34 to 73 clinical isolates of Clostridium difficile to 24 antimicrobial agents, including 18 beta-lactams, 4 fluoroquinolones, clindamycin, and metronidazole were examined. Metronidazole was the most active (MIC for 90% of the isolates [MIC90], 0.5 microgram/ml), followed by the carbapenems (Sch 34343, 4 micrograms/ml; imipenem, 8 micrograms/ml) and the antipseudomonas penicillins (piperacillin, 8 micrograms/ml; ticarcillin, 32 micrograms/ml; carbenicillin, 32 micrograms/ml). A monobactam (aztreonam) and most cephalosporins were either highly inactive (cefoxitin, cefuroxime, cefotiam, cefsulodin, ceftizoxime, cefbuperazone, and cefotaxime), with an MIC90 of greater than or equal to 128 micrograms/ml, or moderately inactive (ceftriaxone, cefmenoxime, cefoperazone, ceftazidime, and moxalactam), with an MIC90 of greater than or equal to 32 micrograms/ml. Clindamycin (MIC90, 32 micrograms/ml) and the fluoroquinolones (ciprofloxacin, 8 micrograms/ml; A-56619, 8 micrograms/ml; A-56620, 8 micrograms/ml; norfloxacin, 32 micrograms/ml) were only variably active. These in vitro data per se may not necessarily predict the relative risks for C. difficile-associated diarrhea or colitis during therapy with these agents. However, these data, in concert with knowledge of drug bioavailability in feces and the broad-spectrum antimicrobial activity on the resident bowel flora, may provide additional insight into the mechanisms and predictability of this complication with these agents. Careful monitoring for the emergence of C. difficile and fecal cytotoxin and for diarrhea during therapy with these agents is clearly indicated.