Novel giardicidal compounds bearing proton pump inhibitor scaffold proceeding through triosephosphate isomerase inactivation.

Giardiasis is a worldwide parasitic disease that affects mainly children and immunosuppressed people. Side effects and the emergence of resistance over current used drugs make imperative looking for new antiparasitics through discovering of new biological targets and designing of novel drugs. Recently, it has determined that gastric proton-pump inhibitors (PPI) have anti-giardiasic activity. The glycolytic enzyme, triosephosphate isomerase (GlTIM), is one of its potential targets. Therefore, we employed the scaffold of PPI to design new compounds aimed to increase their antigiardial capacity by inactivating GlTIM. Here we demonstrated that two novel PPI-derivatives (BHO2 and BHO3), have better anti-giardiasic activity than omeprazole in concentrations around 120-130 µM, without cytotoxic effect on mammal cell cultures. The derivatives inactivated GlTIM through the chemical modification of Cys222 promoting local structural changes in the enzyme. Furthermore, derivatives forms adducts linked to Cys residues through a C-S bond. We demonstrated that PPI can be used as scaffolds to design better antiparasitic molecules; we also are proposing a molecular mechanism of reaction for these novel derivatives.

[Antimicrobial resistance characteristics of clinical isolates of Streptococcus pyogenes]. / Características de la resistencia antimicrobiana de una colección clínica de Streptococcus pyogenes.

OBJECTIVE: To determine the antibiotic susceptibility of recent isolates of Streptococcus pyogenes and to evaluate the prevalence of macrolide-resistant phenotypes. MATERIAL AND METHODS: In 1999, we conducted a cross-sectional study at Mexico Children's Hospital "Federico Gomez", to analyze one hundred strains of S. pyogenes isolated from 1992 to 1998, in children with uncomplicated pharyngotonsillitis. Strains were frozen at the bacteriology lab until they were analyzed. Strains were tested for susceptibility against some beta-lactams, macrolides and clindamycin. Double-disk testing was carried out to evaluate erythromycin-resistant phenotypes. Data are presented using central tendency measures. RESULTS: All tested strains were not resistant to beta-lactams and clindamycin; 16% of the strains were resistant to macrolides and all of them belonged to phenotype M. CONCLUSIONS: Susceptibility testing is recommended to identify possible changes in antibiotic resistance to streptococci.

Clinical outcome of invasive infections in children caused by highly penicillin-resistant Streptococcus pneumoniae compared with infections caused by penicillin-susceptible strains.

BACKGROUND: In this report based on data from the Institutional Surveillance System during 1994-1998, we document the continuing emergence of drug-resistant Streptococcus pneumoniae strains at the Hospital Infantil de Mexico Federico Gómez in Mexico City. METHODS: We evaluate the clinical course of 49 invasive pneumococcal infection outside the central nervous system (CNS) by a number of factors including the site, severity, and place where the infection was acquired, the underlying health of the patient, and the adequacy of antimicrobial therapy. RESULTS: An underlying illness was present in 21 of 49 (43%) patients, 37 (75%) patients had taken previous antimicrobial therapy, and 25% of the infections were nosocomially acquired. Overall, 25 of 49 (51%) of the pneumococcal strains tested were pencillin-resistant; strains with the highest resistance to penicillin were also resistant to cephalosporins. Twenty-two percent of all strains were considered to be multidrug-resistant. Eleven of 25 penicillin-resistant strains were identified as multidrug-resistant, i.e., to erythromycin, TMP/SMX, and chloramphenicol. Ten serotypes accounted for 88% of the isolates, the most frequent serotypes being 23F, 14, 19V, 6A, and 6B. The overall case-fatality rate was 37% (18 of 49), with most deaths occurring within 3-5 days after antibiotic therapy was initiated. There was no difference in the case fatality rate between children with penicillin-nonsusceptible and penicillin-susceptible pneumococcal infections; instead; case-fatality rate correlated with severity of illness on admission and presence of underlying disease. CONCLUSIONS: Characterizing groups at risk for invasive pneumococcal disease could aid in the development of preventive programs and increase the benefits from wide use of future conjugated vaccines.

[Clinico-microbiological characteristics of meningitis caused by penicillin-resistant Streptococcus pneumoniae]]. / Características clínico-microbiológicas de la meningitis por Streptococcus pneumoniae resistente a la penicilina.

OBJECTIVE: To evaluate the susceptibility to antibiotics of Streptococcus pneumoniae isolated from cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment and outcome among children infected with strains either susceptible or resistant to penicillin and cephalosporin. MATERIAL AND METHODS: A total of 38 children with pneumococcal meningitis were prospectively enrolled in the Institutional Surveillance Program for Pneumococcal Infections during 1994-1998. Clinical and laboratory data were collected by chart review. RESULTS: Of the 38 children, 24 (63%) were less than 2 years of age, 11 (28.9%) had drug-resistant S. pneumoniae, 18.4% had intermediate resistance, 10.5% high level resistance and 2.6% also showed high level resistance to cefotaxime. The only associated factors (by Fisher's exact test) associated to resistance were: previous use of antibiotics (p = 0.2), underlying disease (p < 0.001). Course of illness and clinical course were similar for children infected with penicillin or cefotaxime susceptible, vs. non-susceptible strains. CONCLUSIONS: Current levels of S. pneumoniae resistance to penicillin and cephalosporin are not associated to an increase in mortality in children with meningitis.

Prevalence, incidence, and determinants of syphilis in female commercial sex workers in Mexico City.

GOAL: To determine the prevalence and the incidence of serologic markers for syphilis, and the characteristics associated with the risk of infection in female commercial sex workers in Mexico City. To identify female commercial sex workers at greater risk of infection with syphilis. STUDY DESIGN: The authors performed a cross-sectional study of 3,100 female commercial sex workers who sought human immunodeficiency virus testing at a National Council on AIDS clinic between January 1992 and April 1993. The authors collected information about socioeconomic and demographic characteristics, history of sexually transmitted diseases, sexual practices, and preventive measures against such diseases. All of the women provided a blood sample for identification of infection markers and in a subgroup of 1,802 women, repeat samples were obtained to estimate the rate of seroconversion to syphilis. RESULTS: Prevalence of syphilis was 8.2%, with an incidence of 2.4 per 100 person years. A positive linear relation between age and time working in commercial sex and prevalence of infection markers was observed. Women with less education, born in states other than Mexico City, and who worked on the street had significantly greater risks of infection with syphilis. CONCLUSIONS: Frequency of infection by both estimators is relatively low in the women studied. Characteristics related with periods of exposure such as age and time working in commercial sex, as well as socioeconomic and demographic characteristics, such as place of birth, education, and type of work site, were significantly related to the frequency of infection.

PIP: The goal of this study was to determine the prevalence and the incidence of serologic markers for syphilis and the characteristics associated with the risk of infection in female commercial sex workers (CSWs) in Mexico City. It also sought to identify female CSWs at greater risk of infection with syphilis. The authors performed a cross-sectional study of 3100 female CSWs who sought human immunodeficiency virus testing at a National Council on AIDS clinic between January 1992 and April 1993. The authors collected information about socioeconomic and demographic characteristics, history of sexually transmitted diseases, sexual practices, and preventive measures against such diseases. All of the women provided a blood sample for identification of infection markers, and in a subgroup of 1802 women repeat samples were obtained to estimate the rate of seroconversion to syphilis. Prevalence of syphilis was 8.2%, with an incidence of 2.4/100 person-years. A positive linear relation between age and time working in commercial sex and prevalence of infection markers was observed. Women with less education, born in states other than Mexico City, and who worked on the street had significantly greater risks of infection with syphilis. Frequency of infection by both estimators is relatively low in the women studied. Characteristics related to periods of exposure such as age and time working in commercial sex, as well as socioeconomic and demographic characteristics, such as place of birth, education, and type of work site, were significantly related to the frequency of infection.

[Prevalence of antitreponemal antibodies in 3,098 female prostitutes in Mexico City]. / Prevalencia de anticuerpos antitreponémicos en 3098 mujeres dedicadas a la prostitución en la ciudad de México.

This paper describes a serological survey applied to 3098 female commercial sex workers, in order to determine the prevalence of syphilis. The women attend regularly an AIDS orientation center sponsored by CONASIDA in Mexico City. The laboratory tests included the rapid plasma reagin assay (presumptive analysis) and the fluorescent treponemal antibody-absorption technique (confirmatory test). No primary syphilis cases were detected and the prevalence of latent asymptomatic syphilis was 8.2% (255/3098). The sensitivity and specificity of the presumptive test compared to the confirmatory test were 74% and 98% respectively, and the positive predictive value was 77% and the negative predictive value 98%. All seropositive women received the standard penicillin treatment for syphilis. Considerations of importance are offered regarding interpretation and usefulness of this kind of research.

[The resistance and serotyping of 83 strains of Streptococcus pneumoniae isolated from asymptomatic carriers and ill children]. / Resistencia y serotipificación de 83 cepas de Streptococcus pneumoniae aisladas de niños portadores asintomáticos y enfermos.

Eight-three isolates of Streptococcus pneumoniae obtained from children hospitalized with several infections in Mexico City and Cuernavaca, and from healthy children attending a day-care center in Cuernavaca, from January to September 1992, were screened for antimicrobial resistance patterns by in vitro susceptibility testing against antimicrobial agents of potential use in the treatment of diseases caused by S. pneumoniae (39 infected patients and 44 from healthy children). 21.6% of strains were resistant to penicillin, 52% of the strains were multiresistant without a commun pattern. Children attending a day-care center had a higher rate of S. pneumoniae strains resistant to one or more antimicrobial than hospitalized children. Serotypes or serogroups 6, 23F, 14 and 19 were most prevalent. There are evidence that strain 23F has an intercontinental link, this strain is associated with disseminated diseases and multiresistance to antimicrobials. The results indicate that changes can occur in the susceptibility of S. pneumoniae and that selective susceptibility testing and epidemiologic studies in hospitalized patients and children in day-care centers are necessary.

[Human papillomavirus infection in women with and without abnormal cervical cytology]. / Infección por el virus del papiloma humano en mujeres con y sin citología cervical anormal.

This study sought to define the prevalence rates of human papillomavirus (HPV) infection and cytologic abnormalities in 3,257 sexually active females 13 to 45 years of age, undergoing routine cervical cytologic screening in the outpatient clinic of an urban hospital. One hundred and fifty patients (4.6%) showed cytologic evidence of cervical human papillomavirus infection (abnormal Pap). We selected a control group (n = 150) with negative cervical cytologic smears. Cells collected were analysed for HPV-DNA by PCR amplification method with probes for HPV types 6.11, 16.18 and 33. The HPV-DNA was detected in 21/300 (7.0%). The prevalence of cervical HPV-DNA types among women with negative cytology was 5.3% (8/150) and 8.6% (13/150) among women with abnormal Pap. The risk of HPV infection seems to be related with age at first intercourse, younger age and number of sexual partners. We did not find relation with the use of oral contraceptives smoking and history of prior sexually transmitted disease.

[Prevalence of antibodies against cytomegalovirus in women of reproductive age]. / Prevalencia de anticuerpos contra citomegalovirus en mujeres en edad reproductiva.

In order to know the prevalence of antibodies to cytomegalovirus in healthy women, we conducted a seroimmunological survey among 1,885 women, ages 13 to 44 years old, living in a suburban area of Cuernavaca City. Overall, 91.6 per cent of women were seropositive and 8.4 per cent seronegative. The prevalence was not significantly different among women of different ages. Nine out of 10 persons already had antibodies at age 14. One out of ten 15-20 years old women represent the maximum risk of primary infection and, at the same time they represent the population with greatest possibilities of getting pregnant. We found a strong relationship of low education, low income, promiscuity, house without public services and early onset of sexual activity with the presence of antibodies to cytomegalovirus. The risk of exposure to primary infection decreases as these epidemiological markers improve.

[Presence of human Herpes simplex virus-2 (HSV-2) in women attending a clinic for cervico-uterine cancer control]. / Presencia del virus herpes simple-2 (HSV-2) en mujeres que asisten a una clínica de control de cáncer cervicouterino.

For this prospective study, 284 women were recruited who attended a cancer detection (Papanicolaou testing) program and appeared to be healthy. The objective was to obtain cervicovaginal samples from this group and culture them on human foreskin fibroblasts to isolate and identify Herpes simplex virus by immunofluorescence with monoclonal antibodies. A total of 12 women (4.2%) were positive for the virus; upon comparison of various sociodemographic factors in positive and negative culture patients, it was possible to establish certain associations as follows: The presence of Herpes simplex virus type 2 was related to age, start of sexual life, number of sex partners, lower education and minimum income. Other markers observed in infected women were mucopurulent cervicitis, typical and non-typical confluent ulcerations and minor disruptions of the epithelium. The knowledge of this subclinical or somewhat asymptomatic Herpes prevalence should be considered to prevent further spread among couples and also to avoid the risk of reactivation in pregnant women.

In vitro activity of several antimicrobial agents against genital mycoplasmas.

The increasing resistance of genital mycoplasmas to tetracyclines is a serious problem, since this group of antibiotics is one of the few that is effective against virtually all species of mycoplasmas. Tetracyclines are also used to treat many sexually transmitted diseases. In this study, we assessed the susceptibility of Mycoplasma hominis and Ureaplasma urealyticum to macrolides, tetracyclines, spectinomycin, and trospectomycin by the agar dilution method. For M hominis, trospectomycin was the most active agent. Spectinomycin, tetracycline, and doxycycline had comparable mycoplasmatic activity, and the macrolides were ineffective. Against U urealyticum, spectinomycin and trospectomycin were the most active drugs, and were at least twofold more active than the macrolides and tetracyclines.

[Prevalence of cervicovaginal infections caused by Chlamydia trachomatis among female population of the city of Cuernavaca, Morelos]. / Prevalencia de infección cervicovaginal por Chlamydia trachomatis en población femenina de la ciudad de Cuernavaca, Morelos.

The chlamydiae are a genetically diverse group of bacteria with a unique intracellular development cycle. The spectrum of clinical manifestations of Chlamydia trachomatis infections in the female includes cervicitis, acute urethral syndrome, pelvic inflammatory disease, salpingitis and the risk of exposure of infants born through an infected birth canal who may develop inclusion conjunctivitis and/or pneumonia. In order to determine the prevalence of cervicovaginal infections caused by C. trachomatis in female population in Cuernavaca, Morelos, we studied 2,407 sexually active women from a suburban area. Genital specimens were collected from each woman and cultured in McCoy cell monolayers. Detection of the bacteria was done by staining with fluorescein-conjugated monoclonal antibodies (Syva Microtrak, Palo Alto CA). 97 of them were culture-positive for C. trachomatis, with and overall prevalence of 4.02 per cent. The most important clinical symptom observed in 47 of the infected patients was an increased or altered vaginal discharge.

[Infection in pregnancy as a causal factor in premature membrane rupture and preterm labor]. / Infección durante el embarazo como factor causal de ruptura prematura de membranas y de parto pretérmino.

This article discusses recent evidence pointing to an infectious etiology of premature rupture of the membranes and preterm labor. We conclude that antepartum infection is strongly related to preterm labor, premature rupture of the membranes and perinatal morbidity and mortality.

[The prevention of urinary infection during pregnancy in patients with asymptomatic bacteriuria]. / Prevención de la infección urinaria durante la gestación en pacientes con bacteriuria asintomática.

A prospective study was carried out in which quantitative clean-voided urine cultures, were obtained at the first clinic visit from 986 consecutive pregnant women, followed to delivery to assess the maternal and pediatric finding associated with maternal asymptomatic bacteriuria. Patients to be evaluated were divided in two groups: Treatment group (TG) with 42/46 patients that were treated with nitrofurantoin 100 mg a day during 10 days, and control group (CG) with 45/46 patients that were not treated. Patients who failed were given a second course of nitrofurantoin. The patients who remained infected were given further treatment (cephalexin). Primary treatment was successful in 85%, 10% more with the second course and 5% were failure treatment. There was a highly significant difference in the incidence of symptomatic bacteriuria (pyelonephritis), premature deliver, prematurity and other perinatal events in patients with persistent infection. Eradication of asymptomatic bacteriuria reduced the risk of pre-term deliveries and lower infant birth weights for gestational age.

[Acute cystourethritis during pregnancy]. / Cistouretritis aguda durante la gestación.

A prospective study was carried out in 103/863 obstetric patients with cystitis characterized by urinary urgency and frequency, dysuria, pyuria and suprapubic discomfort in the absence of systemic symptoms such as fever and costovertebral angle tenderness. The association of symptomatic lower urinary tract infection with low-count bacteriuria (10(2)-10(5) UFC/mL of urine) was present in all the patients. The incidence of cystourethritis was about 12%, most of the infections occurred at the first trimester. To learn whether a multiple-dose of nitrofurantoin or ampicillin is safe and effective therapy for acute uncomplicated urinary tract infections, 103 symptomatic pregnant women were randomly grouped to receive oral nitrofurantoin (100 mg t.i.d.) or ampicillin (500 mg t.i.d.) for five days. Seventeen patient were excluded since they did not return for follow-up. Escherichia coli was isolated in 67% of infections. Overall cure varied from 87% to 89%, without any great differences between the regimens. Nine patients had asymptomatic bacteriuria in the course of pregnancy, four developed acute pyelonephritis and one of them had abnormal intravenous pyelogram.

[Detection of endocervical chlamydia infections by comparing the Papanicolaou staining test and direct immunofluorescence]. / Detección de infección endocervical por clamidia comparando la tinción de Papanicolaou con inmunofluorescencia directa.

The association of infection with Chlamydia trachomatis and cytologic changes on Papanicolaou smear was examined in 453 sexually active postmenarcal female subjects attending the cytology service for routine Papanicolaou smear. We described inflammatory and epithelial cell patterns that permit the detection of group of women with and without cervicitis at high risk for cervical chlamydial infection. We confirmed the infection by direct immunofluorescence using monoclonal antibodies. Ninety-five of 453 women had cervicitis (20.9%) chlamydial inclusions were noted by Papanicolaou in 26 patients with cervicitis and in 61 without cervicitis. Direct stain with fluorescein-conjugated monoclonal antibodies demonstrated elementary bodies of C. trachomatis in 42/453 women, 24 had cervicitis and 18 without cervicitis. One of two patients with cervical smears with chlamydial inclusions as "changes suggestive of chlamydial infection" by Papanicolaou was confirmed by inmmunofluorescence. We calculated the efficay of the Papanicolaou smear as a diagnostic technique: the sensitivity was 0.27, the specificity was 0.80, the predictive value of o positive test was 0.29. In order to compare the efficiency with immunofluorescence the sensitivity was 0.25, specificity 0.94 and the positive predictive value was 0.57. Using the epithelial changes interpreted as inflammatory, we had the highest sensitivity with both tests, 0.76 to Papanicolaou and 0.90 to immunofluorescence, specificity is near 100% for both tests, cytology tended to be more efficient in identifying women without infection than in identifying those with infection.