Communitywide cryptosporidiosis outbreak associated with a surface water-supplied municipal water system--Baker City, Oregon, 2013.

Cryptosporidium, a parasite known to cause large drinking and recreational water outbreaks, is tolerant of chlorine concentrations used for drinking water treatment. Human laboratory-based surveillance for enteric pathogens detected a cryptosporidiosis outbreak in Baker City, Oregon during July 2013 associated with municipal drinking water. Objectives of the investigation were to confirm the outbreak source and assess outbreak extent. The watershed was inspected and city water was tested for contamination. To determine the community attack rate, a standardized questionnaire was administered to randomly sampled households. Weighted attack rates and confidence intervals (CIs) were calculated. Water samples tested positive for Cryptosporidium species; a Cryptosporidium parvum subtype common in cattle was detected in human stool specimens. Cattle were observed grazing along watershed borders; cattle faeces were observed within watershed barriers. The city water treatment facility chlorinated, but did not filter, water. The community attack rate was 28·3% (95% CI 22·1-33·6), sickening an estimated 2780 persons. Watershed contamination by cattle probably caused this outbreak; water treatments effective against Cryptosporidium were not in place. This outbreak highlights vulnerability of drinking water systems to pathogen contamination and underscores the need for communities to invest in system improvements to maintain multiple barriers to drinking water contamination.

Epidemiological and genetic characteristics of norovirus outbreaks in long-term care facilities, 2003-2006.

To identify the epidemiological and genetic characteristics of norovirus (NoV) outbreaks and estimate the impact of NoV infections in an older population, we analysed epidemiological and laboratory data collected using standardized methods from long-term care facilities (LTCFs) during 2003-2006. Faecal specimens were tested for NoV by real-time reverse transcriptase-polymerase chain reaction. NoV strains were genotyped by sequencing. Of the 234 acute gastroenteritis (AGE) outbreaks reported, 163 (70%) were caused by NoV. The annual attack rate of outbreak-associated NoV infection in LTCF residents was 4%, with a case-hospitalization rate of 3·1% and a case-fatality rate of 0·5%. GII.4 strains accounted for 84% of NoV outbreaks. Median duration of illness was longer for GII.4 infections than non-GII.4 infections (33 vs. 24 h, P<0·001). Emerging GII.4 strains (Hunter/2004, Minerva/2006b, Terneuzen/2006a) gradually replaced the previously dominant strain (Farmington Hills/2002) during 2004-2006. NoV GII.4 strains are now associated with the majority of AGE outbreaks in LTCFs and prolonged illness in Oregon.

Bond lengths in free molecules of buckminsterfullerene, c60, from gas-phase electron diffraction.

Electron diffraction patterns of the fullerene C(60) in the gaseous state have been obtained by volatilizing it from a newly designed oven-nozzle at 730 degrees C. The many peaks of the experimental radial distribution curve calculated from the scattered intensity are completely consistent with icosahedral symmetry for the free molecule. On the basis of this symmetry assumption, least-squares refinement of a model incorporating all possible interatomic distances led to the values r(g)(C(1)-C(2)) = 1.458(6) angstroms (A) for the thermal average bond length within the five-member ring (that is, for the bond fusing five- and six-member rings) and r(g)(C(1)-C(6)) = 1.401(10) A for that connecting five-member rings (the bond fusing six-member rings). The weighted average of the two bond lengths and the difference between them are the values 1.439(2) A and 0.057(6) A, respectively. The diameter of the icosahedral sphere is 7.113(10) A. The uncertainties in parentheses are estimated 2sigma values.

Discordant tuberculin skin and interferon-gamma tests during contact investigations: a dilemma for tuberculosis controllers.

Current recommendations conflict over the appropriate use of interferon-gamma whole blood assays to screen for tuberculosis (TB) infection in contact investigations. We report here on a worksite TB contact investigation in which tuberculin skin test (TST) and QuantiFERON-TB Gold (QFT-G) were both used to identify infection among 61 co-workers. Of the 27 (44%) who had a TST > or =15 mm, 11 (41%) had negative QFT-G, raising concerns that QFT-G may not be sufficiently sensitive when used alone in contact investigations. The questionable performance of QFT-G in this setting is not unexpected, as the negative predictive value of a test decreases with increasing prevalence.

Inhibition of the phosphatidylinositol-specific phospholipase C from Bacillus cereus by a monoclonal antibody binding to a region with sequence similarity to eukaryotic phospholipases.

Bacterial phosphatidylinositol-specific phospholipases C (PI-PLC) display similar substrate specificity as their eukaryotic counterparts involved in signal transduction of insulin and Ca2(+)-mobilizing hormones, and are used in the study of the novel glycosylphosphatidylinositol-protein anchors (GPI-anchors). For the investigation of structure-function aspects of the PI-PLC secreted from Bacillus cereus cells, a panel of murine monoclonal antibodies was generated and shown to be specific for the PI-PLC polypeptide in enzyme-linked immunosorbent assays and Western blots. Two of the monoclonals inhibited reactions catalyzed by the bacterial enzyme in vitro: hydrolysis of phosphatidylinositol and the release of bovine erythrocyte acetylcholinesterase from its GPI-anchor. At saturating concentrations of inhibitory antibody only a few percent of the enzyme activity remained. The epitope recognized by one of the inhibitory antibodies, A72-24, was mapped by proteolytic digestion, protein sequencing, and Western blotting of the generated fragments. The data indicate that at least part of the epitope resides within an 8 kDa-stretch of the bacterial PI-PLC (Gln-45 - Lys-122). Essentially the same segment of the bacterial polypeptide has previously been shown to display limited amino acid sequence similarity with several eukaryotic PI-specific phospholipases C (Kuppe, A., Evans, L.M., McMillen, D.A. and Griffith, O.H. (1989) J. Bacteriol. 171, 6077-6083). The results reported here suggest that the conserved peptide of these enzymes may contain functionally important residues.

Eosinophilia-myalgia syndrome. Natural history in a population-based cohort.

BACKGROUND: To determine the natural history of eosinophilia-myalgia syndrome, we followed up all patients with eosinophilia-myalgia syndrome reported to the Oregon Health Division, Portland, during the recent epidemic caused by contaminated tryptophan. METHODS: Patients were interviewed by telephone from 1 to 5 months after illness onset and again at least 12 months after onset. Symptoms (type, onset, and duration), overall disability, treatment, and tryptophan lot and dose were assessed for each patient. RESULTS: Information was obtained for 55 (96%) of 57 case-patients: 53 patients completed interviews and two patients had died. For the 53 patients who were interviewed, symptoms with onset more commonly during the first 3 months of illness included severe myalgias, fatigue, generalized weakness, edema, and rash. Symptoms with later onset included paresthesias, muscle cramps, extremity weakness, and alopecia. At 12 months, 41 patients (77%) continued to report fatigue, 36 (68%) weakness, and 34 (64%) myalgias; 26 patients (49%) had difficulty climbing stairs, 23 (43%) had difficulty getting up from a chair, and 15 (28%) had difficulty holding a cup. Higher doses of tryptophan were correlated with more severe disability, both initially (rs = .33) and at follow-up (rs = .42). Although most patients reported improvement in symptoms at 12 months, only 14 (26%) patients reported that they were able to perform all normal daily activities. CONCLUSIONS: Most patients with eosinophilia-myalgia syndrome in this population-based cohort are still symptomatic 1 year after onset, primarily with the complaints reported early in the illness. The association between degree of disability and daily tryptophan dose suggests that ingestion of varying amounts of contaminant may be responsible, in part, for the severity of symptoms experienced by individual patients.

Where's the beef? The role of cross-contamination in 4 chain restaurant-associated outbreaks of Escherichia coli O157:H7 in the Pacific Northwest.

BACKGROUND: From March through August 1993, outbreaks of Escherichia coli O157:H7 occurred at 4 separate Oregon and Washington steak and salad bar restaurants affiliated with a single national chain. OBJECTIVE: To determine the cause of outbreaks of E coli O157:H7 at 4 chain restaurants. METHODS: Independent case-control studies were performed for each outbreak. Available E coli O157:H7 isolates were subtyped by pulse-field gel electrophoresis and by phage typing. RESULTS: Infection was not associated with beef consumption at any of the restaurants. Implicated foods varied by restaurant but all were items served at the salad bar. Among the salad bar items, no single item was implicated in all outbreaks, and no single item seemed to explain most of the cases at any individual restaurant. Molecular subtyping of bacterial isolates indicated that the first 2 outbreaks, which occurred concurrently, were caused by the same strain, the third outbreak was caused by a unique strain, and the fourth was multiclonal. CONCLUSIONS: Independent events of cross-contamination from beef within the restaurant kitchens, where meats and multiple salad bar items were prepared, were the likely cause of these outbreaks. Meat can be a source of E coli O157:H7 infection even if it is later cooked properly, underscoring the need for meticulous food handling at all stages of preparation.

Trends and risk factors for HIV-1 seropositivity among outpatient children, Kinshasa, Zaire.

To investigate recent trends in pediatric HIV-1 infection and the early impact of a blood screening program begun in one hospital in 1987 in Kinshasa, Zaire, we evaluated 1110 consecutive children seen in the pediatric emergency ward of the city's largest hospital in November 1988. The HIV-1 seroprevalence was 5.0%, not significantly higher than the rate of 3.8% found in 1986 (P = 0.2). The seropositivity rate was bimodally distributed; children less than 6 months of age had a higher rate (12.6%) than children 6-11 months old (1.9%; OR = 7.6; P less than 0.0001) and children 1-13 years old (4.1%; OR = 3.4; P less than 0.0001). Seropositive children greater than or equal to 1 year of age were more likely than seronegative children to be anemic and to have signs of malnutrition. A previous blood transfusion was associated with HIV-1 seropositivity among children greater than or equal to 1 year of age (OR = 5.4, P less than 0.0005), but not among younger children. Fifty-two per cent of seropositive children greater than or equal to 1 year of age received a transfusion (etiological fraction = 42%). The association with seropositivity was higher for those who had received a transfusion before 1987 than for those who had received a transfusion since 1987 (OR = 4.8, P = 0.01). These findings suggest a relatively stable, high pediatric HIV-1 seroprevalence in Kinshasa and a decreased but continued risk of transfusions. Expansion of currently limited blood transfusion screening programs, and the development of new strategies for limiting transfusions and preventing severe anemia, are needed.

PIP: To investigate recent trends in pediatric HIV-1 infection and the early impact of a blood screening program begun in 1 hospital in Kinshasa, Zaire, the authors evaluated 1110 consecutive children seen in the pediatric emergency ward of the city's largest hospital in November 1988. The HIV-1 seroprevalence was 5.0%, not significantly higher than the 3.8% rate found in 1986 (p=0.2). The seropositivity rate was bimodally distributed; children 6 months of age had a higher rate (12.6%) than children 6-11 months old (1.9%; OR+7.6; p0.0001) and children 1-13 years old (4.1%; OR+3.4; p0.0001). Seropositive children or= 1 year of age were more likely than seronegative children to be anemic and to have signs of malnutrition. A previous blood transfusion was associated with HIV-1 seropositivity among children or= 1 year of age (OR=5.4, p0.0005), but not among younger children. 52% of seropositive children or= 1 year of age had received a transfusion (etiological fraction=42%). The association with seropositivity was higher for those who had received a transfusion before 1987 than for those who received 1 since that time (OR=4.8, p=0.01). These findings suggest a relatively stable, high pediatric HIV-1 seroprevalence in Kinshasa and a decreased but continuous risk of transfusions. Expansion of currently limited blood transfusion screening programs and the development of new strategies for limiting transfusions and anemia prevention are necessary.

Early phorbol ester induced release of cell surface fibronectin: direct observation by photoelectron microscopy.

One of the early effects of the phorbol ester tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) on cultured normal fibroblasts is the release of fibronectin into the culture medium. Immunophotoelectron microscopy was used to follow the loss of fibronectin from the upper cell surface of normal human foreskin fibroblasts exposed to TPA. Fibronectin labeled with silver-enhanced colloidal gold-antibody conjugates appears in photoelectron images as streak- and network-like patterns of bright dots against the less photoemissive uncoated cell surface. Labeled fibronectin present beneath the culture is not detected due to the surface-specificity of this technique. Ten to 30 min of exposure to 100 ng/ml TPA in culture medium results in a readily visible decrease in upper cell surface fibronectin. In these experiments, 60 min of exposure to TPA releases nearly all upper cell surface fibronectin, leaving only occasional short streaks of label. In contrast, extracellular matrix fibronectin between cells is apparently more resistant to release and can still be seen in photoelectron images even when the upper cell surface appears to be fibronectin-free. This immunophotoelectron study shows the distribution of fibronectin on fibroblasts at high resolution and demonstrates that the initial fibronectin release resulting from TPA exposure is at the expense of preexisting cell-surface fibronectin. These results also illustrate the application of photoelectron microscopy as a useful technique in cell biology.

Syntheses and anticholinesterase activity of tetrahydrobenzazepine carbamates.

The synthesis of a series of alkylcarbamates of 1,5-methano-2,3,4,5-tetrahydro-1H-2-benzazepin-7-ol is reported. Many of these compounds are potent acetylcholinesterase (AChE) inhibitors. The in vitro AChE inhibition, cholinergic effects, acute toxicity, and elevation of brain acetylcholine levels in vivo of this series of compounds are described. A representative compound, 1d (5.6 mg/kg, po), was able to reverse hemicolinium-3-induced amnesia in the mouse passive avoidance assay.

Syntheses, resolution, and structure-activity relationships of potent acetylcholinesterase inhibitors: 8-carbaphysostigmine analogues.

The synthesis of a series of 1,2,3,3a,8,8a-hexahydroindeno[2,1-b]pyrrole 5-alkylcarbamates and their resolution are reported. These compounds are structurally related to physostigmine with substitution of a methylene group in place of the NMe group at position 8 of physostigmine. Many of these 8-carbaphysostigmine analogues are more potent acetylcholinesterase inhibitors in vitro and less toxic in vivo than physostigmine. The (-)-enantiomer (e.g., 1d and 1g) possessing the same absolute configuration at C3a and C8a as that of physostigmine, is about 6 to 12-fold more potent at inhibiting acetylcholinesterase than the corresponding (+)-enantiomer (e.g., 1e and 1h).

Pitfalls of immunogold labeling: analysis by light microscopy, transmission electron microscopy, and photoelectron microscopy.

The immunogold method is widely used to localize, identify, and distinguish cellular antigens. There are, however, some pitfalls that can lead to nonspecific binding, particularly in cytoskeletal studies with gold probes prepared from small gold particles. We present a list of suggestions for minimizing nonspecific binding, with particular attention to two problems identified in this study. First, we find that the method used to prepare the colloidal gold particles affects the degree of nonspecific binding. Second, the standard BSA-stabilized small gold probes evidently possess exposed regions that bind to the proteins of cytoskeletal preparations. This was investigated in whole-mount cytoskeletal preparations of cultured cells by use of light microscopy, transmission electron microscopy, and photoelectron microscopy of silver-enhanced specimens. Gold probes were made from approximately 5-nm particles generated by reduction of HAuCl4 with three different reducing agents: white phosphorus, sodium borohydride, and citrate-tannic acid. All three preparations stabilized in the conventional way showed significant levels of nonspecific binding, which was highest with citrate-tannic acid. This problem was largely solved with all three types of probes by including fish gelatin in the probe buffer, by substituting fish gelatin for the BSA stabilizer used to prepare the probes, or by pre-adsorption methods. Application of these techniques resulted in clear immunogold labeling patterns with minimal nonspecific background.

Silver-enhanced colloidal gold as a cell surface marker for photoelectron microscopy.

Colloidal gold labeling in conjunction with silver enhancement was investigated as a labeling technique for photoelectron microscopy (PEM). PEM uses UV-stimulated electron emission to image uncoated cell surfaces, and markers for cell surfaces need to be sufficiently photoemissive to be clearly visible against this background. Label contrast provided by 6 nm or 20 nm colloidal gold markers alone was compared to that provided by 6 nm markers after silver enhancement, using both direct and indirect labeling methods for fibronectin on human fibroblast cell surfaces. In all cases, details of the fibrillar fibronectin labeling distribution which were barely discernible before silver enhancement became highly visible against the cellular surface features. Two factors evidently contribute to the pronounced increase in label contrast with silver enhancement: (1) Increased particle size, which was documented by transmission electron microscopy, and (2) increased photoemission resulting from a silver coating on the enhanced gold markers, compared with the protein coating on the unenhanced gold markers. These data demonstrate that silver enhancement of colloidal gold labeling patterns in PEM images is a highly effective method for localization of specific sites on cell surfaces.

Outbreak of erythromycin-resistant staphylococcal conjunctivitis in a newborn nursery.

We investigated an outbreak of erythromycin-resistant Staphylococcus aureus conjunctivitis in a hospital newborn nursery that used erythromycin eye ointment to prevent ophthalmia neonatorum. Cases occurred in 2 clusters; 20 (14%) of 146 infants in the nursery developed conjunctivitis from July through October, 1987; and 5 (7%) of 69 infants in the nursery developed conjunctivitis during April and May, 1988. A case-control study of the first cluster demonstrated that culture-confirmed cases were more likely than controls to have received prophylactic erythromycin eye ointment or their initial bath from one nurse (odds ratio, 9.0; P = 0.01) or to have been delivered by one physician (odds ratio, 12.7; P = 0.03). The nurse was the only staff person to have a nasopharyngeal culture which yielded erythromycin-resistant S. aureus. Control measures, instituted in October, 1987, included using silver nitrate drops instead of erythromycin eye ointment for prophylaxis; however, in January, 1988, the hospital resumed use of erythromycin eye ointment. No additional cases were identified until mid-April, 1988, when the second cluster of cases occurred. At that time the hospital reinstituted the use of silver nitrate and no additional cases were identified. This investigation illustrates the potential for conjunctival infection with an antimicrobial-resistant pathogen when antimicrobials are used to prevent ophthalmia neonatorum.

Tobacco smoke as a risk factor for meningococcal disease.

BACKGROUND: Since 1992 the US Pacific Northwest has experienced a substantial increase in the incidence of serogroup B meningococcal disease. The current meningococcal polysaccharide vaccine is poorly immunogenic in young children and does not protect against N. meningitidis serogroup B. Defining alternative approaches to the prevention and control of meningococcal disease is of considerable public health importance. METHODS: We performed a case-control study comparing 129 patients in Oregon and southwest Washington with 274 age- and area-matched controls. We used conditional logistic regression analysis to determine which exposures remained associated with disease after adjusting for other risk factors and confounders and calculated the proportion of disease attributable to modifiable exposures. RESULTS: After adjustment for all other significant exposures identified, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children < 18 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI) 1.6 to 8.9)], with 37% (CI 15 to 65) of all cases in this age group potentially attributable to maternal smoking. Adult patients were more likely than controls to have a chronic underlying illness (OR 10.8, CI 2.7 to 43.3), passive tobacco smoke exposure (OR 2.5, CI 0.9 to 6.9) and to smoke tobacco (OR 2.4, CI 0.9 to 6.6). Dose-response effects were seen for passive smoke exposure and risk of disease in all age groups. CONCLUSION: Tobacco smoke exposure independently increases the risk of developing meningococcal disease.

Evaluation of a statewide bicycle helmet law via multiple measures of helmet use.

OBJECTIVES: To evaluate an Oregon law requiring bicyclists younger than 16 year to wear a helmet and to compare methods of measuring helmet use. DESIGN: Four prelaw and postlaw statewide helmet use surveys: (1) statewide observations, (2) middle school observations, (3) classroom self-report surveys, and (4) a statewide adult telephone survey. SETTING: Oregon. SUBJECTS: Statewide observations, 3313 child bicyclists at 13 sites; middle school observations, 995 child bicyclists at 33 randomly selected middle schools; classroom self-report surveys, fourth, sixth, and eighth graders in 448 classrooms (ie, 8955 students) before the law was effected and 456 classrooms (ie, 9811 students) after the law was effected in 66 randomly selected schools; and statewide telephone survey, 1219 randomly called parents of 1437 children younger than 16 years. MAIN OUTCOME MEASURES: Prelaw and postlaw helmet use and ownership and knowledge and opinion about the law. RESULTS: Observed helmet use among youth was 24.5% before the law was effected and 49.3% after the law was effected. School-observed use increased from 20.4% to 56.1%. Classroom survey self-reported "always" use of helmets increased from 14.7% to 39.4%; reported use on the day of the survey increased from 25.8% to 76.0%. Telephone survey-reported "always" helmet use increased from 36.8% to 65.7%. Younger children and girls were more likely to use helmets. Most students (ie, 87.8%) and parents (ie, 95.4%) knew about the law; however, only 42.6% of children thought the law was a good idea. CONCLUSIONS: We conclude that (1) the law increased helmet use; (2) although use estimates differ, all helmet surveys showed similar degrees of prelaw and postlaw change; and (3) half of child bicyclists are still not wearing helmets, indicating a need for additional promotion of helmet wearing. Laws seem to be an effective way to increase helmet use.

Plasmodium falciparum-associated anemia in children at a large urban hospital in Zaire.

Chloroquine-resistant Plasmodium falciparum malaria and human virus (HIV) infection through blood transfusions used to treat malaria-associated anemia are causes of increasing morbidity and mortality among children in Africa. To evaluate the role of malaria and other risk factors for pediatric anemia, we conducted a study of children brought to the emergency ward of a large urban hospital in Kinshasa, Zaire. A total of 748 children ages six through 59 months were enrolled; 318 (43%) children were anemic (hematocrit < 33%), including 74 (10%) who were severely anemic (hematocrit < 20%). Plasmodium falciparum parasites were detected in 166 children (22%); hematocrits for these children (mean 25.8%) were significantly lower than for aparasitemic children (mean 33.7%; P < 10(-6)). Fever with splenomegaly (odds ratio [OR] = 6.5, P = 0.02), parasitemia (OR = 3.5, P < 0.001), lower socioeconomic status (OR = 2.0, P = 0.004), and malnutrition (OR = 1.8, P = 0.06) were independently associated with anemia in a multivariate model. Recent antimalarial therapy was also associated with a lower hematocrit, suggesting that chloroquine may have aggravated the anemia. A reassessment of the effectiveness of strategies to diagnose and treat malaria and malnutrition is necessary to decrease the high prevalence of anemia and the resultant high rate of blood transfusions in areas endemic for malaria and HIV.

HIV seroprevalence in emergency department patients: Portland, Oregon, 1988-1991.

OBJECTIVES: In Portland, OR: 1) to determine the changes in HIV seroprevalence for ED patients from 1988 to 1991, 2) to define the characteristics of the HIV-positive ED patient, 3) to determine the hepatitis B seroprevalence of HIV-seropositive ED patients, and 4) to demonstrate the feasibility of an ED population-based surveillance investigation. METHODS: A prospective, multiyear observational, cross-sectional, multicenter, population-based seroprevalence study was performed using seven urban hospital EDs. Serologic testing for HIV and hepatitis B was performed on excess blood obtained from ED patients. Four sampling periods were used at each hospital at 14-month intervals starting June 1988 and ending December 1991. The blood specimens were obtained concurrently at all the participating hospitals. RESULTS: Of 1,681 patients, 17 (1.0%) were HIV-positive. The HIV seroprevalence rate was relatively stable over time: 0.5% (2/444) in 1988, 1.7% (7/396) in 1989, 1% (3/296) in 1990, and 0.9% (5/545) in 1991. Most (94%) HIV patients were men, 100% were white, 81% were > or = 30 years old. Most (59%) of the HIV-positive patients also were positive for hepatitis B core antibody. Many (76%) of the HIV-positive patients were known to be positive by the emergency health care worker. CONCLUSION: HIV seroprevalence among the ED patients in Portland, OR, was generally stable from 1988 to 1991. Many HIV-positive patients also were hepatitis B-positive, thus representing a double occupational infectious disease risk to ED personnel. A significant minority (24%) of the HIV-positive patients were not known to be HIV-positive by the ED personnel. Universal precautions and hepatitis B immunization are paramount for reducing the risk of infectious disease due to exposure to body fluids.

Biological applications of photoelectron imaging: a practical perspective.

Photoelectron imaging is finding a promising niche in the study of biological specimens. The features of photoelectron imaging that contribute to its uniqueness for this application are described. Image formation and the major contrast mechanisms of photoelectron microscopy, material contrast and topographical contrast are reviewed and illustrated with examples of photoelectron images of cultured cells and of DNA. General considerations in sample choice and preparation are also presented. Strategies for photoelectron labeling are discussed including the use of immunogold labeling, silver enhancement and cesium-based photocathodes.

(6R,8S)-(2-benzimidazolyl)hydroxymethylpenicillanic acids as potent antibacterial agents and beta-lactamase inhibitors.

(6R,8S)-(2-Benzimidazolyl)hydroxymethylpenicillanic acids (1a-1x) are potent antibacterial agents and beta-lactamase inhibitors against Gram-positive bacteria and Haemophilus influenzae. The corresponding (6R,8R)-isomers (2a-2x), the 6,6-spiro benzimidazole-penam alcohol (3), (7R,9S)-(2-benzimidazolyl)hydroxymethylcephalosporanic acid (4), and 6 beta-(2-benzimidazolyl)aminopenicillanic acid (5) are much less active as antibacterials or beta-lactamase inhibitors. The syntheses and structure-activity relationships of these compounds are discussed. Antibacterial activity and beta-lactamase inhibition data are presented.