Sustained antimicrobial activity of tigecycline against methicillin-resistant Staphylococcus aureus (MRSA) from United States Medical Centers from 2004 through 2008.

Tigecycline, a glycylcycline, has been approved by the United States Food and Drug Administration (USA-FDA) for the treatment of complicated skin and skin structure infections, intra-abdominal infections and community-acquired bacterial pneumonia. based on broth microdilution minimum inhibitory concentration (MIC) testing, tigecycline demonstrated sustained high activity (MIC(50/90), 0.12/0.25 mg/L) against a contemporary collection (10,242) of methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) collected from 32 USA hospitals over a 5-year period (2004-2008). Tigecycline MIC distribution did not vary significantly during the study period and only three isolates (0.03%) were non-susceptible at USA-FDA breakpoints. Vancomycin (MIC(90), 1 mg/L), trimethoprim/sulfamethoxazole (MIC( 90), <0.5 mg/L) and linezolid (MIC(90), 2 mg/L) were also very active. The results of this study indicate that tigecycline potency and spectrum against MRSA have not changed since its initial regulatory approval by the USA-FDA.

Influenza epidemiology and characterization of influenza viruses in patients seeking treatment for acute fever in Cambodia.

The epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in Cambodia. In December 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. Fever was defined as tympanic membrane temperature >38 degrees C. From December 2006 to December 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Of these patients, 1151 (27.2%) were positive for influenza. Cough (68.8% vs. 50.5%, P < 0.0001) and sore throat (55.0% vs. 41.9%, P < 0.0001) were more often associated with laboratory-confirmed influenza-infected patients compared to influenza-negative enrollees. A clear influenza season was evident between July and December with a peak during the rainy season. Influenza A and B viruses were identified in 768 (66.3%) and 388 (33.7%) of the influenza-positive population (n = 1153), respectively. In December 2008, passive surveillance identified infection of the avian influenza virus H5N1 in a 19-year-old farmer from Kandal province who subsequently recovered. From a subset of diagnostic samples submitted in 2007, 15 A(H1N1), seven A(H3N2) and seven B viruses were isolated. The predominant subtype tested was influenza A(H1N1), with the majority antigenically related to the A/Solomon Island/03/2006 vaccine strain. The influenza A(H3N2) isolates and influenza B viruses analysed were closely related to A/Brisbane/10/2007 or B/Ohio/01/2005 (B/Victoria/2/87-lineage) vaccine strains, respectively. Phylogenetic analysis of the HA1 region of the HA gene of influenza A(H1N1) viruses demonstrated that the Cambodian isolates belonged to clade 2C along with representative H1N1 viruses circulating in SE Asia at the time. These viruses remained sensitive to oseltamivir. In total, our data suggest that viral influenza infections contribute to nearly one-fifth of acute febrile illnesses and demonstrate the importance of influenza surveillance in Cambodia.

Case series study of traveler's diarrhea in U.S. military personnel at Incirlik Air Base, Turkey.

Military personnel with traveler's diarrhea (n=202) while deployed to Incirlik Air Base, Turkey, from June to September 2002 were evaluated for pathogen-specific immune responses. Serologic and fecal immunoglobulin A (IgA) titers to enterotoxigenic Escherichia coli antigens (CS6, CS3, and LT) were quite low. In contrast, subjects with Campylobacter infections had high serologic and fecal IgA responses.

Serological evidence of arboviral infection and self-reported febrile illness among U.S. troops deployed to Al Asad, Iraq.

Understanding the epidemiology of current health threats to deployed U.S. troops is important for medical assessment and planning. As part of a 2004 study among U.S. military personnel deployed to Al Asad Air Base, in the western Anbar Province of Iraq, over 500 subjects were enrolled, provided a blood specimen, and completed a questionnaire regarding history of febrile illness during this deployment (average approximately 4 months in country). This mid-deployment serum was compared to pre-deployment samples (collected approximately 3 months prior to deployment) and evaluated for seroconversion to a select panel of regional arboviral pathogens. At least one episode of febrile illness was reported in 84/504 (17%) of the troops surveyed. Seroconversion was documented in nine (2%) of deployed forces tested, with no association to febrile illness. Self-reported febrile illness was uncommon although often debilitating, and the risk of illness due to arbovirus infections was relatively low.

Antimicrobial susceptibility trends among Escherichia coli and Shigella spp. isolated from rural Egyptian paediatric populations with diarrhoea between 1995 and 2000.

Antimicrobial susceptibility testing was performed on 3,627 isolates of Escherichia coli and 180 isolates of Shigella spp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance for E. coli and Shigella spp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin-sulbactam, 57.2% and 42.5% for trimethoprim-sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenic E. coli (NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenic E. coli (ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin-sulbactam and tetracycline among all E. coli isolates. Increasing rates of resistance were observed for trimethoprim-sulphamethoxazole in ETEC isolates and Shigella spp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates of E. coli and Shigella spp. from children in rural Egypt.

Tea consumption and risk of cancer of the colon and rectum.

The association between tea consumption and risk of colon and rectal cancers was investigated in a population-based case-control study conducted in Iowa (United States). Colon (n = 685) and rectal (n = 655) cancer cases age 40-85 yr were identified through the Iowa Surveillance, Epidemiology, and End Results (SEER) Cancer Registry (86% response rate); controls (n = 2,434) were frequency matched by sex and 5-yr age group (80% response rate). The usual adult consumption of tea (hot and iced), along with other information including dietary data, was self-reported using a mailed questionnaire. Total tea consumption (cups/day) was categorized as none (reference category), low (< 3.1), medium (3.1-5.0), and high (> 5.0), with cut points for tea consumers based on the 75th and 90th percentiles of use among controls. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals. There was no association between total tea consumption and colon cancer (ORs = 1.0, 1.1, 1.3, and 0.7) or rectal cancer (ORs = 1.0, 0.9, 1.4, and 1.0) after adjustment for age, sex, education, physical activity, smoking history, and intake of coffee, fiber, and fruits and vegetables. Results were similar when hot tea and iced tea were evaluated individually. Further adjustment for other colorectal cancer risk factors did not alter these results. There was no association with proximal or distal colon cancer. There was also no interaction between tea consumption and any of the dietary variables or total fluid on risk of colon or rectal cancer, with the exception of a suggestive positive association between an increasing frequency of tea consumption and colon cancer risk among current smokers (multivariate ORs = 1.0, 1.4, 2.0, and 1.8; P for trend = 0.1), but not among never smokers (multivariate ORs = 1.0, 1.0, 1.1, and 0.4; P for trend = 0.3). These data do not support an overall association, either positive or negative, between tea consumption and risk of colon or rectal cancer in this Mid-western US population.

Lifestyle and anthropometric risk factors for prostate cancer in a cohort of Iowa men.

PURPOSE: Several lines of evidence suggest that prostate cancer has a hormonal etiology. We evaluated factors known to modulate the endocrine system, including alcohol and tobacco use, physical activity, and obesity as risk factors for prostate cancer. METHODS: Cancer-free controls who participated in a population-based case-control study from 1986-1989 (81% response rate) were followed through 1995 for cancer incidence by linkage to the Iowa Cancer Registry; 101 incident prostate cancers were identified. RESULTS: Compared with non-users of alcohol, men who consumed <22 grams alcohol per week (relative risk [RR] = 1.1; 95% Confidence Interval [CI] 0.6-2.1), 22-96 grams alcohol per week (RR = 2.6; 95% CI 1.4-4. 6) and >96 grams alcohol per week (RR = 3.1; 95% CI 1.5-6.3) were at increased risk of prostate cancer after adjustment for age, family history of prostate cancer, body mass index, total energy, and intake of carbohydrate, linoleic acid, lycopene, retinol, and red meat (p for trend < 0.0001). The respective RRs were similar when assessing type of alcohol consumed (beer, wine or liquor) or when well-differentiated, localized tumors were excluded. Body mass index was only weakly and positively associated with prostate cancer after adjustment for age, but this association strengthened after multivariate adjustment and exclusion of well-differentiated, localized tumors. For the latter tumors, men with a BMI of 24.1-26.6 kg/m(2) and >26.6 kg/m(2) were at elevated risk compared to men with a BMI <24.1 kg/m(2). Tobacco use (cigarettes, cigar/pipe, chewing tobacco and snuff use), height, weight, and both leisure and occupational physical activity were not associated with risk of prostate cancer in this cohort. CONCLUSIONS: These data suggest that in white men obesity is a risk factor for more clinically significant prostate cancer and confirm limited previous reports showing that alcohol consumption is positively associated with prostate cancer and that this risk is not limited to any specific type of alcohol.

Tea consumption and risk of bladder and kidney cancers in a population-based case-control study.

Recent epidemiologic studies have suggested that tea may be protective against cancers of the urinary tract. The authors examined the association between usual adult tea consumption and risk of bladder and kidney cancers in a population-based case-control study that included 1,452 bladder cancer cases, 406 kidney cancer cases, and 2,434 controls. For bladder cancer, the age- and sex-adjusted odds ratios (OR) (95% confidence intervals (CI)) referent to nonusers of tea were 0.9 (0.7, 1.1) for <1.0 cup/day, 1.0 (0.8, 1.2) for 1.0-2.6 cups/day, and 0.9 (0.7, 1.1) for >2.6 cups/day (cutpoints for users based on the tertile distribution among controls). When more extreme cutpoints were used, persons who consumed >5 cups/day (>90th percentile) had a suggestive decreased risk (OR = 0.7; 95% CI 0.5, 1.0), but there was no evidence of a dose-response relation. In analyses stratified by median total beverage intake (2.6 liters/day), there was an inverse association with tea use among persons who consumed less than the median (OR = 0.5; 95% CI 0.3, 0.8) but no association for persons who consumed at or above the median. In contrast, for kidney cancer, there was no association with tea use. Adjustment for site-specific risk factors did not alter these results. This study offers only minimal support for an inverse association between tea consumption and bladder or kidney cancer risk.

Pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae in a respiratory chemoprophylaxis intervention study using azithromycin.

OBJECTIVES: A prospective assessment of the pharyngeal colonization prevalence rates for Streptococcus pyogenes and Streptococcus pneumoniae before and after an azithromycin chemoprophylaxis intervention clinical trial in a cohort of US Marine Corps trainees. In addition, the minimum inhibitory concentrations (MICs) for all streptococcal isolates, for azithromycin, penicillin, erythromycin and cefotaxime are reported. METHODS: Between November 1994 and March 1995, 1108 asymptomatic male US Marine Corps trainees, located in Southern California, were randomly assigned to one of three intervention groups: (1) weekly oral azithromycin, 500 mg (n = 362); (2) 1.2 MU benzathine penicillin G, intramuscularly once (n = 374); or (3) no chemoprophylaxis (n = 372). Subjects provided both a pre- and post-training pharyngeal culture and microbial analysis was conducted to determine the colonization status of each study subject. RESULTS: The pretraining colonization prevalence was 1.2% for S. pneumoniae and 2.4% for S. pyogenes. There was no statistical difference in pretraining prevalence between the three treatment groups for either organism. Post-training pharyngeal cultures revealed an overall prevalence of 1.1% with no difference between treatment arms. However, the overall post-training prevalence of S. pyogenes colonization increased to 4.8%, with the azithromycin group having significant evidence of protection (0.7%) in comparison with the no-treatment group (8.2%). The Etest method demonstrated no significant difference in the MIC50, MIC90, and MIC ranges between pre- and post-training isolates for any of the tested drugs. CONCLUSION: The use of azithromycin as a chemoprophylactic agent to reduce the colonization and subsequent infection of streptococcal respiratory disease among healthy adult male military recruits may be beneficial.

A cohort study of farming and risk of prostate cancer in Iowa.

Although farming has been linked to prostate cancer mortality, few investigations have addressed its association with prostate cancer incidence. We followed a population-based cohort of 1,177 cancer-free men for up to 9 years and identified 81 incident prostate cancers. Men whose usual occupation was farmer were at an increased risk of prostate cancer after adjustment for age, smoking, alcohol, and dietary factors (RR = 1.7; 95% CI = 1.0-2.7). Exclusion of well-differentiated, localized tumors slightly strengthened the association (RR = 2.0; 95% CI = 1.1-3.6). Risk was confined to older (age 70+ years) farmers (RR = 2.2; 95% CI = 1.1-4.3); we found no evidence of an effect among younger farmers (RR = 1.0; 95% CI = 0.4-2.1).

Family history and prostate cancer risk in a population-based cohort of Iowa men.

A family history of prostate cancer has been associated with prostate cancer risk in most prior studies, and more limited data suggest that a family history of breast cancer may also be important; however, there are no data from a population-based cohort study of prostate cancer incidence that adjusts for major confounders. We conducted follow-up through 1995 on 1557 men, ages 40-86 years, who were randomly selected (81% response rate) as cancer-free controls for a population-based case-control study conducted in Iowa from 1987-1989. Family history of cancer in parents and siblings was obtained using a mailed questionnaire. Incident cancers and deaths were ascertained through linkages to state and national databases; 101 incident cases of prostate cancer were identified. At baseline, 4.6% of the cohort reported a family history of prostate cancer in a brother or father, and this was positively associated with prostate cancer risk after adjustment for age [relative risk (RR) = 3.2; 95% confidence interval (CI), 1.8-5.7] or after multivariate adjustment for age, alcohol, and dietary factors (RR = 3.7; 95% CI, 1.9-7.2). Risk was greater if a brother had prostate cancer (RR = 4.5; 95% CI, 2.1-9.7) than if a father had prostate cancer (RR = 2.3; 95% CI, 1.0-5.3). Also at baseline, 9.6% of the cohort had a family history of breast and/or ovarian cancer in a mother or sister, and this was positively associated with prostate cancer risk (age-adjusted RR = 1.7; 95% CI, 1.0-3.0; multivariate RR = 1.7; 95% CI, 0.9-3.2). Men with a family history of both prostate and breast/ovarian cancer were also at increased risk of prostate cancer (RR = 5.8; 95% CI, 2.4-14). There was no association with a family history of colon cancer. Exclusion of well-differentiated, localized tumors did not alter these findings. These data from an incidence study confirm that a family history of prostate cancer is a strong prostate cancer risk factor after adjustment for dietary and other risk factors, and suggest that selection and recall bias have not had an important influence on most case-control study results. These data also support the idea that a family history of breast cancer may also be a prostate cancer risk factor.

Asymptomatic sexually transmitted disease prevalence in four military populations: application of DNA amplification assays for Chlamydia and gonorrhea screening.

The prevalence of asymptomatic chlamydial and gonococcal infections in male and female military populations was determined using urine-based ligase chain reaction DNA amplification assays (DAAs). Cross-sectional surveys in four military settings revealed an overall prevalence of asymptomatic chlamydial infection of 4.2% (56/1338). This included 3.4% (21/618) of Western Pacific shipboard US Marine Corps enlisted men; 5.2% (21/406) of male marines shore-based in Okinawa, Japan; 2.7% (5/183) of female enlisted US Navy subtender personnel in dry dock; and 6.9% (9/131) of shore-based female naval personnel in San Diego. No gonococcal infections were detected. All subjects were treated within 2 weeks of screening; none of them had progressed to symptomatic disease. General population-based screening for asymptomatic sexually transmitted diseases, and in particular chlamydial infection, can be successfully implemented using urine-based DAA tests. Benefits are maximized in a population in which compliance for follow-up therapy is high.

Weekly oral azithromycin as prophylaxis for agents causing acute respiratory disease.

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.

Evaluation of pertussis in U.S. Marine Corps trainees.

One hundred twenty male U.S. Marine Corps trainees with histories of at least 7 days of cough underwent evaluation for Bordetella pertussis infection by culture, B. pertussis-specific polymerase chain reaction (PCR) analysis, and serology. Antibody levels in preexposure, acute-phase, and convalescent-phase serum samples were measured in a microagglutination assay and in enzyme linked immunosorbent assays (ELISAs) for IgG and IgA antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3. Culture and PCR analysis revealed that none of the patients were positive for B. pertussis; however, 20 of 120 trainees had serological evidence of B. pertussis infection. Of these cases, one was confirmed by a rise in the level of antibody to pertussis toxin, and six were classified as probable by increases in levels of antibodies measured by two or more assays. Of the 20 individuals with serological evidence of infection, 16 had rises in levels of antibodies to fimbriae or agglutinating antibodies. The utility of ELISA for detecting antibodies to fimbriae and the microagglutination assay for diagnosing pertussis in adults should be evaluated by application to larger and more diverse study populations. These results indicate that pertussis should be considered in the diagnosis of coughing illness in military populations.

Mycoplasma pneumoniae: a frequent cause of pneumonia among U.S. Marines in southern California.

From August 1993 through April 1994, U.S. Marines (98% male, median age 20 years) who were hospitalized with radiographically confirmed pneumonia were prospectively studied for evidence of acute Mycoplasma pneumoniae infection. Overall, 32 (36.4%) of the 88 patients with paired sera had evidence of acute infection by an elevated immunoglobulin M titer (22.7%), a 4-fold rise in immunoglobulin G titer (9.1%), a positive polymerase chain reaction result (11.1%), and/or a positive culture (5.8%). No specific symptoms or clinical findings were strong predictors of M. pneumoniae infection. Among patients with evidence of acute M. pneumoniae infection, admitting clinicians chose other pathogens as more likely etiologic agents 46.4% of the time, and over the course of the hospitalization, 10% of patients failed to receive appropriate antibiotics. These data indicate that M. pneumoniae may cause a high proportion of pneumonias among military personnel and should be considered in empiric treatment and prophylaxis.

In vitro antimicrobial activity and MIC quality control guidelines of RPR 106972 (RPR 112808/RPR106950): a novel orally administered streptogramin combination. The Quality Control Study Group.

RPR 106972 is a novel oral streptogramin combination with reported therapeutic potency against Gram-positive and certain respiratory tract pathogens. MICs for RPR 106972, quinupristin/dalfopristin, and seven comparison drugs were determined by the reference methods against 337 strains selected to define spectrum and potency. RPR 106972 demonstrated antimicrobial activity against oxacillin-susceptible and -resistant Staphylococcus aureus (MIC ranges of 0.12 to 2 micrograms/ml and 0.5 to 2 micrograms/ml, respectively), and coagulase-negative staphylococci were also inhibited by RPR 106972 (MIC90, < or = 0.5 microgram/ml) and quinupristin/dalfopristin (MIC90, < or = 0.25 microgram/ml). Against all streptococcal strains tested (including penicillin-resistant pneumococcus), RPR 106972 was highly active with MIC results at < or = 1 microgram/ml. RPR 106972 inhibited Corynebacterium jeikeium (MIC90, 0.5 microgram/ml). Moraxella catarrhalis (MIC90, 0.25 microgram/ml), and some Haemophilus influenzae (MIC50, 2 micrograms/ml). RPR 106972 and quinupristin/dalfopristin demonstrated little activity against Enterococcus faecalis (MIC90s, 4 to 32 micrograms/ml) as compared to Enterococcus faecium (MIC90s, 0.5 to 1 microgram/ml) and other Enterococcus ssp. (MIC90s, 1 microgram/ml). Studies to establish MIC quality-control guidelines indicated the following ranges: for E. faecalis ATCC 29212, 0.5 to 4 micrograms/ml; for S. aureus ATCC 29213, 0.25 to 1 microgram/ml; and for Streptococcus pneumoniae ATCC 49619, 0.06 to 0.5 microgram/ml. The results of this study indicate that the in vitro activity of RPR 106972 against Gram-positive bacteria and selected Gram-negative respiratory organisms is promising and warrants additional studies of pharmacokinetics, and in vivo infection model dynamics.

Evaluation of in vitro spectra of activity of azithromycin, clarithromycin, and erythromycin tested against strains of Neisseria gonorrhoeae by reference agar dilution, disk diffusion, and Etest methods.

The macrolide-azilide susceptibility testing (agar dilution, disk diffusion, Etest) criteria for 105 Neisseria gonorrhoeae strains were evaluated. In addition, the potencies of azithromycin, clarithromycin, and erythromycin were studied. The most active macrolide-azilide agent was azithromycin (MIC at which 90% of the isolates are inhibited [MIC90], 0.5 microgram/ml) compared with clarithromycin (MIC90, 1.5 to 2 micrograms/ml) and erythromycin (MIC90, 2 to 4 micrograms/ml). The Etest (AB Biodisk, Solna, Sweden) was observed to produce MIC results very similar to those of the reference agar dilution test (GC agar base), with 100% of the results within 1 log2 dilution step of the reference MICs. The disk diffusion test zone diameters for all three drugs correlated at an acceptable level (r = -0.81 to -0.92) with the reference agar dilution MICs. Interpretive criteria for susceptibility were proposed for azithromycin at a MIC of < or = 2 micrograms/ml and a disk diffusion test zone of > or = 25 mm. No category for resistance was proposed because of the paucity of strains for which MICs were > 2 micrograms/ml. These tentative criteria should be further validated by correlations with clinical trial data for gonococcal strains (as they emerge) that have azithromycin MICs above the proposed susceptible category range.

Antigonococcal activity of 11 drugs used for therapy or prophylaxis of malaria.

Antibacterial agents are often used in malarial endemic areas for antimalarial prophylaxis (such as doxycycline and clindamycin). Gonococcal infections may coexist in the same geographic area, thus becoming suppressed by compounds directed toward malarial parasites. We tested 11 drugs with activity for Plasmodium species against 105 Neisseria gonorrhoeae strains. Traditional or investigational antimalarials such as arteflene (Ro 42-1611), chloroquine, primaquine, pyrimethamine, quinacrine, and quinine were observed to be inactive. Fansidar (sulfadoxine-pyrimethamine) and mefloquine possess marginal action in a minority of gonococcus strains (< 10%). Doxycycline [minimum inhibitory concentration inhibiting 90% of tested strains (MIC 90) 2 micrograms/ml] and azithromycin (MIC 90, 0.5 microgram/ml) among the antibacterials were very active, indicating a dual role as antimalarial and antigonococcal agents. Thus, the gonorrhea and sexually transmitted disease epidemiologic data from geographic regions where doxycycline or newer macrolides may be used for malarial prophylaxis or therapy could be significantly altered.

Evaluation of the standardized disk diffusion and agar dilution antibiotic susceptibility test methods by using strains of Neisseria gonorrhoeae from the United States and Southeast Asia.

Presently, most Neisseria gonorrhoeae testing is based on beta-lactamase tests and agar dilution with common therapeutic agents. The National Committee for Clinical Laboratory Standards (NCCLS) recently described a disk diffusion test that produced results similar to the reference agar dilution method for the antibiotic susceptibility of N. gonorrhoeae. We obtained 71 gonococcal isolates from active-duty males aboard a United States Navy vessel while deployed in the Western Pacific during 1989. In addition, 47 isolates of N. gonorrhoeae were obtained from sexually transmitted disease clinics within the branch clinic operations of the Naval Hospital, San Diego (SD), and tested. Antibiotic susceptibility tests by using the NCCLS agar dilution and disk diffusion techniques were compared. Among the Southeast Asia (SEA) isolates, 47% were beta-lactamase producers compared with 10.5% of the SD isolates. The mean MICs (SEA/SD) in micrograms per milliliter for both groups were as follows: penicillin, 88/15; tetracycline, 2.2/0.95; erythromycin, 1.2/0.49; ceftriaxone, 0.016/0.012; cefotaxime, 0.034/0.03; cefuroxime, 0.44/0.17; cefoxitin, 1.3/0.97; spectinomycin, 150/131; ciprofloxacin, 0.07/0.034; norfloxacin, 0.77/0.29; lomefloxacin, 0.15/0.0.056; and ofloxacin, 0.07/0.036. The established NCCLS interpretive criteria for both susceptibility methods appear applicable to domestic gonococcal strains. However, modifications may be necessary for the more antimicrobial agent-resistant SEA isolates on the basis of the clinical success and cure rates following the indicated single-dose regimens for the geographic region.

Site-directed mutagenesis to probe protein folding: evidence that the formation and aggregation of a bovine growth hormone folding intermediate are dissociable processes.

Bovine growth hormone (bGH) forms a stable folding intermediate that aggregates at elevated concentrations (greater than 10 microM). Thermodynamic and kinetic studies have shown that the formation of this bGH folding intermediate and its aggregation are separate processes, implying that selective modifications of bGH can lead to their independent modulation. In addition, a bGH region that includes amino acid residues 109-133 appears to be directly involved in this aggregation process. Human growth hormone (hGH), which is unable to aggregate via this mechanism, differs from the bovine primary sequence at eight positions within this protein region. We have characterized the folding of a bGH analogue that contains the hGH sequence between amino acid residues 109-133 (8H-bGH) at low and high concentrations. The equilibrium folding characteristics of bGH and 8H-bGH are similar when monitored at low protein concentrations (less than or equal to 2 microM). The wild-type and analogue proteins have equivalent denaturation midpoints when equilibrium unfolding is monitored by the use of far-UV circular dichroism, second-derivative UV, or fluorescence. In addition, the enhanced fluorescence that is associated with the formation of the bGH monomeric folding intermediate (Havel, H. A., et al. (1988) Biochim. Biophys. Acta 955, 154-163) is observed for 8H-bGH under similar conditions. In contrast, partial denaturation of 8H-bGH at higher concentrations (greater than 2 microM) leads to significantly less aggregation than is observed for bGH. This result is obtained from near-UV CD spectroscopy, kinetic folding, size-exclusion chromatography, and dynamic light-scattering data.(ABSTRACT TRUNCATED AT 250 WORDS)