The type 1 pili regulator gene fimX and pathogenicity island PAI-X as molecular markers of uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) fall within a larger group of isolates producing extraintestinal disease. UPEC express type 1 pili as a critical virulence determinant mediating adherence to and invasion into urinary tract tissues. Type 1 pili expression is under regulation by a family of site-specific recombinases, including FimX, which is encoded from a genomic island called PAI-X for pathogenicity island of FimX. Using a new multiplex PCR, fimX and the additional PAI-X genes were found to be highly associated with UPEC (144/173 = 83.2 %), and more prevalent in UPEC of lower urinary tract origin (105/120 = 87.5 %) than upper urinary tract origin (39/53 = 74 %; P<0.05) or commensal isolates (28/78 = 36 %; P≤0.0001). The Fim-like recombinase gene fimX is the only family member that has a significant association with UPEC compared to commensal isolates. Our results indicate PAI-X genes, including the type 1 pili regulator gene fimX, are highly prevalent among UPEC isolates and have a strong positive correlation with genomic virulence factors, suggesting a potential role for PAI-X in the extraintestinal pathogenic E. coli lifestyle.

Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are common among women and frequently recur. Depletion of vaginal lactobacilli is associated with UTI risk, which suggests that repletion may be beneficial. We conducted a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (Lactin-V; Osel) for prevention of recurrent UTI in premenopausal women. METHODS: One hundred young women with a history of recurrent UTI received antimicrobials for acute UTI and then were randomized to receive either Lactin-V or placebo daily for 5 d, then once weekly for 10 weeks. Participants were followed up at 1 week and 10 weeks after intervention and for UTIs; urine samples for culture and vaginal swabs for real-time quantitative 16S ribosomal RNA gene polymerase chain reaction for L. crispatus were collected. RESULTS: Recurrent UTI occurred in 7/48 15% of women receiving Lactin-V compared with 13/48 27% of women receiving placebo (relative risk [RR], .5; 95% confidence interval, .2-1.2). High-level vaginal colonization with L. crispatus (≥10(6) 16S RNA gene copies per swab) throughout follow-up was associated with a significant reduction in recurrent UTI only for Lactin-V (RR for Lactin-V, .07; RR for placebo, 1.1; P < .01). CONCLUSIONS: Lactin-V after treatment for cystitis is associated with a reduction in recurrent UTI. Larger efficacy trials of this novel preventive method for recurrent UTI are warranted. CLINICAL TRIALS REGISTRATION. NCT00305227.

Quantitative metabolomics reveals an epigenetic blueprint for iron acquisition in uropathogenic Escherichia coli.

Bacterial pathogens are frequently distinguished by the presence of acquired genes associated with iron acquisition. The presence of specific siderophore receptor genes, however, does not reliably predict activity of the complex protein assemblies involved in synthesis and transport of these secondary metabolites. Here, we have developed a novel quantitative metabolomic approach based on stable isotope dilution to compare the complement of siderophores produced by Escherichia coli strains associated with intestinal colonization or urinary tract disease. Because uropathogenic E. coli are believed to reside in the gut microbiome prior to infection, we compared siderophore production between urinary and rectal isolates within individual patients with recurrent UTI. While all strains produced enterobactin, strong preferential expression of the siderophores yersiniabactin and salmochelin was observed among urinary strains. Conventional PCR genotyping of siderophore receptors was often insensitive to these differences. A linearized enterobactin siderophore was also identified as a product of strains with an active salmochelin gene cluster. These findings argue that qualitative and quantitative epi-genetic optimization occurs in the E. coli secondary metabolome among human uropathogens. Because the virulence-associated biosynthetic pathways are distinct from those associated with rectal colonization, these results suggest strategies for virulence-targeted therapies.

Endometrial histopathology in patients with laparoscopic proven salpingitis and HIV-1 infection.

STUDY OBJECTIVE: To identify sensitive and specific histological criteria for endometritis in women with laparoscopically-confirmed acute salpingitis. METHODS: Women, age 18-40 years of age presenting with complaints of lower abdominal pain ≤2 weeks and no antibiotics use in past two weeks, were enrolled. They underwent clinical examination, screening for HIV; other sexually transmitted infections plus endometrial biopsy sampling for histopathology. Diagnostic laparoscopy confirmed the diagnosis of acute salpingitis. Controls were women undergoing tubal ligation and HIV-1 infected women asymptomatic for genital tract infection. RESULTS: Of 125 women with laparoscopically-confirmed salpingitis, 38% were HIV-1 seropositive. Nineteen HIV-1 negative controls were recruited. For the diagnosis of endometritis, ≥1 plasma cells (PC) and ≥3 polymorphonuclear lymphocytes (PMN) per HPF in the endometrium had a sensitivity of 74% for HIV-1-seropositive, 63% for HIV-1-seronegative women with a specificity of 75% and positive predictive value of 85% regardless of HIV-1-infection for predicting moderate to severe salpingitis. For HIV-1-seronegative women with mild salpingitis, ≥1 PC and ≥3 PMN had a sensitivity of 16% and a PPV of 57%. CONCLUSION: Endometrial histology, did not perform well as a surrogate marker for moderate to severe salpingitis, and failed as a surrogate marker for mild salpingitis.

Phylogenetic analysis of Chlamydia trachomatis Tarp and correlation with clinical phenotype.

Chlamydia trachomatis is the leading cause of infectious blindness worldwide and is the most commonly reported pathogen causing sexually transmitted infections. Tarp (translocated actin recruiting phosphoprotein), a type III secreted effector that mediates actin nucleation, is central to C. trachomatis infection. The phylogenetic analysis of tarP from reference strains as well as ocular, genital, and lymphogranuloma venereum (LGV) clinical isolates demonstrated an evolutionary relationship with disease phenotype, with LGV and ocular isolates branched into clades that were separate from the urogenital isolates. The sequence analysis of Tarp indicated a high degree of variability and identified trends within clinical groupings. Tarps from LGV strains contained the highest number of tyrosine-rich repeat regions (up to nine) and the fewest (two) predicted actin binding domains. The converse was noted for Tarp proteins from ocular isolates that contained up to four actin binding domains and as few as one tyrosine-rich repeat region. The results suggest that Tarp is among the few known genes to play a role in C. trachomatis adaptations to specific niches within the host.

Genome sequencing of recent clinical Chlamydia trachomatis strains identifies loci associated with tissue tropism and regions of apparent recombination.

The human pathogen Chlamydia trachomatis exists as multiple serovariants that have distinct organotropisms for different tissue sites. Culture and epidemiologic data have demonstrated that serovar G is more prevalent, while serovar E is less prevalent, for rectal isolates from men having sex with men (MSM). The relative prevalence of these serovars is the opposite for isolates from female cervical infections. In contrast, the prevalence of serovar J isolates is approximately the same at the different tissue sites, and these isolates are the only C-class strains that are routinely cultured from MSM populations. These correlations led us to hypothesize that polymorphisms in open reading frame (ORF) sequences correlate with the different tissue tropisms of these serovars. To explore this possibility, we sequenced and compared the genomes of clinical anorectal and cervical isolates belonging to serovars E, G, and J and compared these genomes with each other, as well as with a set of previously sequenced genomes. We then used PCR- and restriction digestion-based genotyping assays performed with a large collection of recent clinical isolates to show that polymorphisms in ORFs CT144, CT154, and CT326 were highly associated with rectal tropism in serovar G isolates and that polymorphisms in CT869 and CT870 were associated with tissue tropism across all serovars tested. The genome sequences collected were also used to identify regions of likely recombination in recent clinical strains. This work demonstrated that whole-genome sequencing along with comparative genomics is an effective approach for discovering variable loci in Chlamydia spp. that are associated with clinical presentation.

Family history and risk of recurrent cystitis and pyelonephritis in women.

PURPOSE: Recurrent urinary tract infections and pyelonephritis have risk factors suggesting genetic sources. Family history variables indicative of genetic risk merit further investigation. We evaluated the risk of recurrent cystitis and pyelonephritis in women with and those without a family history of urinary tract infection. MATERIALS AND METHODS: We conducted a population based case-control study of 1,261 women 18 to 49 years old enrolled in a Northwest health plan. Participants were cases identified from plan databases with documented recurrent cystitis (431) or pyelonephritis (400). Shared controls (430) were similar age women with no urinary tract infection history. We evaluated the history of urinary tract infection and pyelonephritis in first-degree female relatives (mother, sister[s], daughter[s]) and other covariates, ascertained through questionnaires and computerized databases. RESULTS: Of the cases 70.9% with recurrent cystitis and 75.2% with pyelonephritis, and of the controls 42.4% reported a urinary tract infection history in 1 or more female relative (p <0.001 for each case group vs controls). In both case groups odds ratios were significantly increased for women reporting a urinary tract infection history in their mother, sister(s) or daughter(s). Risk increased with a greater number of affected relatives. In women with 1 vs 2 or more relatives the ORs for recurrent cystitis were 3.1 (95% CI 2.1, 4.7) and 5.0 (3.1, 8.1), and the ORs for pyelonephritis were 3.3 (2.2, 5.0) and 5.5 (3.4, 9.0), respectively. CONCLUSIONS: In these community dwelling women a urinary tract infection history in female relatives was strongly and consistently associated with urinary tract infection recurrence and pyelonephritis. Risk estimates increased with stronger family history indices, suggesting a genetic component for increased susceptibility to these infections.

Identification of concomitant infection with Chlamydia trachomatis IncA-negative mutant and wild-type strains by genomic, transcriptional, and biological characterizations.

Clinical isolates of Chlamydia trachomatis that lack IncA on their inclusion membrane form nonfusogenic inclusions and have been associated with milder, subclinical infections in patients. The molecular events associated with the generation of IncA-negative strains and their roles in chlamydial sexually transmitted infections are not clear. We explored the biology of the IncA-negative strains by analyzing their genomic structure, transcription, and growth characteristics in vitro and in vivo in comparison with IncA-positive C. trachomatis strains. Three clinical samples were identified that contained a mixture of IncA-positive and -negative same-serovar C. trachomatis populations, and two more such pairs were found in serial isolates from persistently infected individuals. Genomic sequence analysis of individual strains from each of two serovar-matched pairs showed that these pairs were very similar genetically. In contrast, the genome sequence of an unmatched IncA-negative strain contained over 5,000 nucleotide polymorphisms relative to the genome sequence of a serovar-matched but otherwise unlinked strain. Transcriptional analysis, in vitro culture kinetics, and animal modeling demonstrated that IncA-negative strains isolated in the presence of a serovar-matched wild-type strain are phenotypically more similar to the wild-type strain than are IncA-negative strains isolated in the absence of a serovar-matched wild-type strain. These studies support a model suggesting that a change from an IncA-positive strain to the previously described IncA-negative phenotype may involve multiple steps, the first of which involves a translational inactivation of incA, associated with subsequent unidentified steps that lead to the observed decrease in transcript level, differences in growth rate, and differences in mouse infectivity.

Prevalence and risk factor analysis of trimethoprim-sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli infection among emergency department patients with pyelonephritis.

BACKGROUND: High rates of resistance to trimethoprim-sulfamethoxazole (TMP-SMX) among uropathogenic Escherichia coli are recognized, and concerns exist about emerging fluoroquinolone resistance. METHODS: Adults presenting to 11 US emergency departments with (1) flank pain and/or costovertebral tenderness, (2) temperature >38 degrees C, and (3) a presumptive diagnosis of pyelonephritis were enrolled; patients for whom 1 uropathogen grew on culture were analyzed. Epidemiologic and clinical data were collected at the time of care. The prevalence of E. coli in vitro antibiotic resistance and risk factors associated with TMP-SMX-resistant E. coli infection were determined. RESULTS: Among 403 women with uncomplicated pyelonephritis caused by E. coli, the mean site rate of E. coli resistance to TMP-SMX was 24% (range, 13%-45%). Mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 1% and 3%, respectively. Only TMP-SMX exposure within 2 days before presentation and Hispanic ethnicity were associated with E. coli resistance to TMP-SMX (compared with resistance rates of approximately 20% among women lacking these risk factors); antibiotic exposure within 3-60 days before presentation, health care setting exposure within 30 days before presentation, history of urinary tract infections, and age >55 years were not associated with E. coli resistance to TMP-SMX. Among 207 patients with complicated pyelonephritis, mean site rates of E. coli resistance to ciprofloxacin and levofloxacin were 5% and 6%, respectively. CONCLUSIONS: These results suggest that the prevalence of TMP-SMX-resistant infection among patients with uncomplicated pyelonephritis is > or =20% in many areas of the United States, and risk stratification cannot identify patients at low risk of infection. Rates of fluoroquinolone-resistant E. coli infection appear to be low among patients with uncomplicated pyelonephritis but higher among those with complicated infections. Fluoroquinolones should remain to be the preferred empirical treatment for women with uncomplicated pyelonephritis.

Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection.

BACKGROUND: Many sex partners of persons with gonorrhea or chlamydial infections are not treated, which leads to frequent reinfections and further transmission. METHODS: We randomly assigned women and heterosexual men with gonorrhea or chlamydial infection to have their partners receive expedited treatment or standard referral. Patients in the expedited-treatment group were offered medication to give to their sex partners, or if they preferred, study staff members contacted partners and provided them with medication without a clinical examination. Patients assigned to standard partner referral were advised to refer their partners for treatment and were offered assistance notifying partners. The primary outcome was persistent or recurrent gonorrhea or chlamydial infection in patients 3 to 19 weeks after treatment. RESULTS: Persistent or recurrent gonorrhea or chlamydial infection occurred in 121 of 931 patients (13 percent) assigned to standard partner referral and 92 of 929 (10 percent) assigned to expedited treatment of sexual partners (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98). Expedited treatment was more effective than standard referral of partners in reducing persistent or recurrent infection among patients with gonorrhea (3 percent vs. 11 percent, P=0.01) than in those with chlamydial infection (11 percent vs. 13 percent, P=0.17) (P=0.05 for the comparison of treatment effects) and remained independently associated with a reduced risk of persistent or recurrent infection after adjustment for other predictors of infection at follow-up (relative risk, 0.75; 95 percent confidence interval, 0.57 to 0.97). Patients assigned to expedited treatment of sexual partners were significantly more likely than those assigned to standard referral of partners to report that all of their partners were treated and significantly less likely to report having sex with an untreated partner. CONCLUSIONS: Expedited treatment of sex partners reduces the rates of persistent or recurrent gonorrhea or chlamydial infection.

Rifalazil retains activity against rifampin-resistant mutants of Chlamydia pneumoniae.

Rifampin-resistant mutants of the obligate intracellular pathogen Chlamydia pneumoniae were isolated and characterized, including strains that contained multiple mutations in the rpoB gene encoding the rifampin binding site. The highest MIC of rifampin against a mutant strain exceeded 100 microg/ml, whereas the highest MIC of rifalazil was 0.125 microg/ml. Derivatives of rifalazil (new chemical entities; NCEs) showed from 2 approximately 4 fold lower MICs, as well as 2 approximately 8 fold lower bactericidal concentrations against both wild type and mutant strains when compared with rifalazil. These results suggest that rifalazil and NCEs are appropriate therapeutic agents for the treatment of C. pneumoniae infections from the point of view of potency and resistance development.

Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women.

BACKGROUND: There is a paucity of data on the efficacy of nitrofurantoin for the treatment of acute uncomplicated cystitis in regimens shorter than 7 days. Evidence-based use of this drug is increasingly important as trimethoprim-sulfamethoxazole resistance among uropathogens increases. METHODS: To assess the efficacy of nitrofurantoin vs trimethoprim-sulfamethoxazole, 338 women aged 18 to 45 years with acute uncomplicated cystitis were randomized to open-label treatment with either trimethoprim-sulfamethoxazole, 1 double-strength tablet twice daily for 3 days, or nitrofurantoin, 100 mg twice daily for 5 days. Clinical cure 30 days after therapy was the main outcome measure. Secondary outcomes included clinical and microbiological cure rates 5 to 9 days after therapy and, for trimethoprim-sulfamethoxazole-treated women, clinical cure stratified by the trimethoprim-sulfamethoxazole susceptibility of the uropathogen. RESULTS: Clinical cure was achieved in 79% of the trimethoprim-sulfamethoxazole group and in 84% of the nitrofurantoin group, for a difference of -5% (95% confidence interval, -13% to 4%). Clinical and microbiological cure rates at the first follow-up visit were also equivalent between the 2 groups. In the trimethoprim-sulfamethoxazole arm, 7 of 17 women (41%) with a trimethoprim-sulfamethoxazole-nonsusceptible isolate had a clinical cure compared with 84% of women with a trimethoprim-sulfamethoxazole-susceptible isolate (P < .001). CONCLUSION: A 5-day course of nitrofurantoin is equivalent clinically and microbiologically to a 3-day course of trimethoprim-sulfamethoxazole and should be considered an effective fluoroquinolone-sparing alternative for the treatment of acute cystitis in women.

Population-based epidemiologic analysis of acute pyelonephritis.

BACKGROUND: Acute pyelonephritis is a potentially severe disease for which there are few population-based studies. We performed a population-based analysis of trends in the incidence, microbial etiology, antimicrobial resistance, and antimicrobial therapy of outpatient and inpatient pyelonephritis. METHODS: A total of 4887 enrollees of Group Health Cooperative, based in Seattle, Washington, who received an International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis of acute pyelonephritis from 1997 through 2001 were identified using computerized records. Diagnoses were linked to urine culture and antibiotic prescription data. Case patients (n=3236) included subjects who had received an inpatient or culture-confirmed outpatient diagnosis of acute pyelonephritis. RESULTS: Among the female population, annual rates of outpatient and inpatient pyelonephritis were 12-13 cases per 10,000 population and 3-4 cases per 10,000 population, respectively; among the male population, the rates were 2-3 cases per 10,000 population and 1-2 cases per 10,000 population, respectively. Rates were relatively stable from year to year. Incidence was highest among young women, followed by infants and the elderly population. The ratio of outpatient to inpatient cases was highest among young women (ranging from 5 : 1 to 6 : 1). Escherichia coli caused 80% of cases of acute pyelonephritis in women and 70% of cases in men and was less dominant in older age groups. Among E. coli strains, the rate of ciprofloxacin resistance increased from 0.2% of isolates to 1.5% of isolates (P=.03), and the rate of trimethoprim-sulfamethoxazole resistance decreased from 25% of isolates to 13% of isolates (P<.01) from 1997 to 2001. Among outpatient cases, the rate of fluoroquinolone use increased from 35% to 61%, whereas the rate of trimethoprim-sulfamethoxazole use decreased from 53% to 32% over the 5-year period (P<.01). CONCLUSIONS: This comprehensive, population-based analysis adds to our limited knowledge of the epidemiology of acute pyelonephritis, especially among outpatients, in whom the majority of cases now occur.

Detection of intracellular bacterial communities in human urinary tract infection.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI. METHODS AND FINDINGS: We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria. CONCLUSIONS: The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.

Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates.

We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.

Clonal isolation of chlamydia-infected cells using flow cytometry.

This manuscript describes a new technique for the microbiological cloning of chlamydia-infected cells using a fluorescence activated cell sorter (FACS). The approach exploits chlamydial acquisition of the fluorescent, Golgi-specific, stain 6-((N-7-(-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-hexanoyl)sphingosine (C6-NBD-cer). This fluorescent lipid is delivered from the Golgi apparatus to the chlamydial inclusion membrane and then to the developmental forms within the inclusion in living, infected cells. Labeling with C6-NBD-cer results in easily identifiable chlamydial inclusions that can then be analyzed and sorted by FACS. This technique was used successfully to sort individual chlamydia-infected cells into individual wells of a culture dish and, in this experimental system, resulted in the isolation of cloned chlamydial isolates. FACS-based sorting was used to isolate clonal populations of prototype strains from Chlamydia trachomatis, C. caviae and C. suis. Recent clinical isolates were also successfully cloned using FACS. The procedure is simple and rapid, with single cloning cycles being completed 24 h post-culture of a sample. It is anticipated that FACS-based sorting of live chlamydia-infected cells will be a significant technical tool for the isolation of clonal populations of any chlamydial strain.

Phase I trial of a Lactobacillus crispatus vaginal suppository for prevention of recurrent urinary tract infection in women.

OBJECTIVES: We performed a phase I trial to assess the safety and tolerance of a Lactobacillus vaginal suppository for prevention of recurrent UTI. METHODS: Premenopausal women with a history of recurrent UTI were randomized to use L. crispatus CTV-05 or placebo vaginal suppositories daily for five days. RESULTS: 30 women were randomized (15 to L. crispatus CTV-05). No severe adverse events occurred. Mild to moderate vaginal discharge and genital irritation were reported by women in both study arms. Seven women randomized to L. crispatus CTV-05 developed pyuria without associated symptoms. Most women had high concentrations of vaginal H202-producing lactobacilli before randomization. L. crispatus, L. jensenii, and L. gasseri were the most common Lactobacillus species identified, with stable prevalence over time. CONCLUSIONS: L. crispatus CTV-05 can be given as a vaginal suppository with minimal sideeffects to healthy women with a history of recurrent UTI. Mild inflammation of the urinary tract was noted in some women.

Population-based genetic epidemiologic analysis of Chlamydia trachomatis serotypes and lack of association between ompA polymorphisms and clinical phenotypes.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases worldwide. Urogenital strains are classified into serotypes and genotypes based on the major outer membrane protein and its gene, ompA, respectively. Studies of the association of serotypes with clinical signs and symptoms have produced conflicting results while no studies have evaluated associations with ompA polymorphisms. We designed a population-based cross-sectional study of 344 men and women with urogenital chlamydial infections (excluding co-pathogen infections) presenting to clinics serving five U.S. cities from 1995 to 1997. Signs, symptoms and sequelae of chlamydial infection (mucopurulent cervicitis, vaginal or urethral discharge; dysuria; lower abdominal pain; abnormal vaginal bleeding; and pelvic inflammatory disease) were analyzed for associations with serotype and ompA polymorphisms. One hundred and fifty-three (44.5%) of 344 patients had symptoms consistent with urogenital chlamydial infection. Gender, reason for visit and city were significant independent predictors of symptom status. Men were 2.2 times more likely than women to report any symptoms (P=0.03) and 2.8 times more likely to report a urethral discharge than women were to report a vaginal discharge in adjusted analyses (P=0.007). Differences in serotype or ompA were not predictive except for an association between serotype F and pelvic inflammatory disease (P=0.046); however, the number of these cases was small. While there was no clinically prognostic value associated with serotype or ompA polymorphism for urogenital chlamydial infections except for serotype F, future studies might utilize multilocus genomic typing to identify chlamydial strains associated with clinical phenotypes.

Effect of human immunodeficiency virus-1 infection on treatment outcome of acute salpingitis.

OBJECTIVE: To examine the effect of human immunodeficiency virus (HIV)-1 infection on treatment outcome of laparoscopically verified acute salpingitis. METHODS: Women aged 18-40 years with laparoscopically verified acute salpingitis received antibiotic therapy that included cefotetan 2 g intravenously and doxycycline 100 mg orally every 12 hours and laparoscopically guided drainage of tuboovarian abscesses of 4 cm or more. Clinical investigators blinded to HIV-1 serostatus used predetermined clinical criteria, including calculation of a clinical severity score and a standard treatment protocol to assess response to therapy. RESULTS: Of the 140 women with laparoscopically confirmed acute salpingitis, 61 (44%) women had mild, 38 (27%) had moderate, and 41 (29%) had severe disease (ie, pyosalpinx, tuboovarian abscesses, or both). Fifty-three (38%) were HIV-1-infected. Severe disease was more common in HIV-1-infected in comparison with HIV-1-uninfected women (20 [38%] compared with 21 [24%], P = .02). Defined as time of hospital discharge or 75% or more reduction in baseline clinical severity score, HIV-1-infected women with severe (6 days [4-16] compared with 5 days [3-9], P = .09) but not those with either mild (4 days [2-6] compared with 4 days [2-6] P = .4) or moderate salpingitis (4 days [3-7] compared with 4 days [3-6] P = .32) tended to take longer to meet criteria for clinical improvement. The need for intravenous clindamycin or additional surgery was not different in HIV-1-infected and uninfected cases (15 [28%] compared with 18 [21%], P = .3). CONCLUSION: Although HIV-1 infection may prolong hospitalization in women with severe salpingitis, all women hospitalized with acute salpingitis responded promptly to antibiotic therapy and surgical drainage regardless of HIV-1 infection status. LEVEL OF EVIDENCE: II-2.

Theodore E. Woodward Award: host-pathogen interactions in community-acquired urinary tract infections.

Community-acquired urinary tract infections continue to be a significant source of morbidity and health care costs. In addition, community-acquired urinary tract infections are an excellent model for studying the interaction of the infecting bacteria and the human host. This review focuses upon five recent areas of progress in understanding host-parasite interactions in urinary tract infection. First, uropathogenic E. coli have been recognized as a specific pathogenic group of organisms characterized by the presence of pathogenecity islands, horizontally-acquired genes encoding various pathogenic phenotypes, including fimbria, other adhesins, lipopolysaccharide, the polysaccharide capsule, various toxins and hemolysins, and siderophores. Second, recent studies indicate that the epithelium plays an active role in the innate host defense against urinary infection, including secretion of chemokines and cytokines, apoptosis of epithelial cells and exfoliation of bacteria-laden epithelial cells. Third, studies in animal models indicate that uropathogenic E. coli invade epithelial cells, forming intracellular communities of organisms and eventually biofilms. These intracellular organisms may persist and form a reservoir from which recurrent infection may develop. Finally, observations suggest that some women may be genetically predisposed to recurrent urinary tract infection and the genes predisposing to recurrent infection are being sought. These new discoveries have improved our understanding of the pathogenesis of these infections and will eventually lead to improved interventions for prevention and therapy.