RESUMO
Background: Frequent use of antibiotics is thought to create selection pressure by clearing susceptible bacteria and allowing resistant bacteria to spread in a community. A cluster-randomized trial comparing 2 different frequencies of mass azithromycin distributions for trachoma provided a convenient experiment for determining the causal relationship between antibiotic consumption and antibiotic resistance. Methods: Twenty-four communities were randomized to either annual or biannual mass azithromycin distributions for trachoma. Randomization was stratified on health catchment area and trachoma prevalence. Swabs were processed for the genetic macrolide resistance determinants ermB and mefA/E in a masked fashion from a random sample of 120 preschool children before treatment and another 120 children after 2 years of mass antibiotics. Results: Macrolide resistance determinants were similar in the 12 annually and 12 biannually treated communities before treatment, with a median prevalence among preschool children of 20% (interquartile range [IQR], 10%-40%) in each group. By 24 months, macrolide resistance determinants were found more commonly in the biannually treated communities (median, 60% [IQR, 50%-80%]) than the annually treated communities (median, 40% [IQR, 20%-40%]; P < .001). Adjusting for baseline, the 24-month prevalence of macrolide resistance determinants in the biannual group was 29.4% higher than that of the annual group (95% confidence interval, 10.5%-56.7%). Conclusions: This randomized trial used direct genetic methods to confirm the causal relationship of community antibiotic consumption and antibiotic resistance. Communities randomized to less frequent use of antibiotics had a significantly lower prevalence of genetic antibiotic resistance determinants. Clinical Trials Registration: NCT00792922.
Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/genética , Macrolídeos/administração & dosagem , Nasofaringe/microbiologia , Seleção Genética , Tracoma/tratamento farmacológico , Administração Oral , Antibacterianos/uso terapêutico , Azitromicina/administração & dosagem , Azitromicina/uso terapêutico , Proteínas de Bactérias/genética , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Lactente , Recém-Nascido , Macrolídeos/uso terapêutico , Masculino , Administração Massiva de Medicamentos , Prevalência , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genéticaRESUMO
Prior studies have theorized that low chlamydial genetic diversity following mass azithromycin treatments for trachoma may create a population bottleneck that prevents the return of infection, but little empirical evidence exists to support this hypothesis. In this study, a single mass azithromycin distribution was administered to 21 communities in the Gurage Zone of Ethiopia in 2003. All children aged 1-5 years had conjunctival swabs performed before treatment and 2 and 6 months after treatment. All swabs positive for Chlamydia trachomatis at 2 months underwent typing of the gene encoding the major outer membrane protein (ompA) of C. trachomatis, as did the same number of swabs per community from the pretreatment and 6-month visits. Diversity of ompA types, expressed as the reciprocal of Simpson's index, was calculated for each community. In total, 15 ompA types belonging to the A and B genovars were identified. The mean diversity was 2.11 (95% confidence interval: 1.79, 2.43) before treatment and 2.16 (95% confidence interval: 1.76, 2.55) 2 months after treatment (P = 0.78, paired t test). Diversity of ompA was not associated with the prevalence of ocular chlamydia (P = 0.76) and did not predict subsequent changes in the prevalence of ocular chlamydia (P = 0.32). This study found no evidence to support the theory that ompA diversity is associated with transmission of ocular chlamydia.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Proteínas da Membrana Bacteriana Externa/genética , Chlamydia trachomatis/genética , Tracoma/microbiologia , Variação Genética , Humanos , Tracoma/tratamento farmacológicoRESUMO
BACKGROUND: Experimental studies have shown that the standard dose of riboflavin (R) or R + ultraviolet-A (UVA) as solo treatment are not able to exterminate Acanthamoeba cysts or even trophozoites. The purpose of this study is to determine whether the application of R + UVA can enhance the cysticidal effects of cationic antiseptic agents in vitro. METHODS: The log of either polyhexamethylene biguanide or chlorhexidine minimal cysticidal concentration in solutions containing riboflavin (concentrations 0.1, 0.05 and 0.025%) plus either Acanthamoeba castellanii cysts or Acanthamoeba polyphaga cysts was determined and compared in groups treated with UVA 30 mW/cm(2) for 30 min and in control groups (with no exposure to UVA). A permutation test was used to determine the P value associated with treatment. RESULTS: Regardless of the riboflavin concentration and UVA treatment condition, no trophozoites were seen in plates where the cysts were previously exposed to cationic antiseptic agent concentrations ≥200 µg/mL for Acanthamoeba castellanii samples and ≥100 µg/mL for A. polyphaga samples. There was no statistical evidence that R + UVA treatment was associated with minimal cysticidal concentration (P = 0.82). CONCLUSION: R + UVA in doses up to 10 times higher than recommended for corneal crosslinking does not enhance the cysticidal effect of either polyhexamethylene biguanide or chlorhexidine in vitro.
Assuntos
Acanthamoeba/efeitos dos fármacos , Desinfetantes/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Raios Ultravioleta , Acanthamoeba/fisiologia , Acanthamoeba/efeitos da radiação , Biguanidas/farmacologia , Clorexidina/farmacologia , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade ParasitáriaRESUMO
BACKGROUND: A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains. METHODS: Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing. RESULTS: Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045). CONCLUSIONS: Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Genes Bacterianos , Humanos , Lactente , Recém-Nascido , Masculino , Tipagem de Sequências Multilocus , Cavidade Nasal/microbiologia , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
BACKGROUND: To determine the relationship between type three secretion genotype and fluoroquinolone resistance for P. aeruginosa strains isolated from microbial keratitis during the Steroids for Corneal Ulcers Trial (SCUT) and for two laboratory strains, PA103 and PAO1. METHODS: Confirmed P. aeruginosa isolates from the SCUT were divided into exoU(+) or exoU(-). The exoU(+) strains contained the gene encoding ExoU, a powerful phospholipase toxin delivered into host cells by the type three secretion system. Isolates were then assessed for susceptibility to fluoroquinolone, cephalosporin, and aminoglycoside antibiotics using disk diffusion assays. Etest was used to determine the MIC of moxifloxacin and other fluoroquinolones. Laboratory isolates in which the exoU gene was added or deleted were also tested. RESULTS: A significantly higher proportion of exoU(+) strains were resistant to ciprofloxacin (p = 0.001), gatifloxacin (p = 0.003), and ofloxacin (p = 0.002) compared to exoU(-) isolates. There was no significant difference between exoU(+) or exoU(-) negative isolates with respect to susceptibility to other antibiotics except gentamicin. Infections involving resistant exoU(+) strains trended towards worse clinical outcome. Deletion or acquisition of exoU in laboratory isolates did not affect fluoroquinolone susceptibility. CONCLUSIONS: Fluoroquinolone susceptibility of P. aeruginosa isolated from the SCUT is consistent with previous studies showing elevated resistance involving exoU encoding (cytotoxic) strains, and suggest worse clinical outcome from infections involving resistant isolates. Determination of exoU expression in clinical isolates of P. aeruginosa may be helpful in directing clinical management of patients with microbial keratitis.
Assuntos
Córnea/microbiologia , Úlcera da Córnea/microbiologia , Farmacorresistência Bacteriana , Infecções Oculares Bacterianas/microbiologia , Fluoroquinolonas/uso terapêutico , Glucocorticoides/uso terapêutico , Pseudomonas aeruginosa/patogenicidade , Idoso , Córnea/patologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/patologia , DNA Bacteriano/genética , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/patologia , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prognóstico , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Acuidade VisualRESUMO
PURPOSE: Outcomes of Acanthamoeba keratitis are often worse in India than in the United States. The goal of this study was to determine whether antiamoebic susceptibility patterns were different when comparing Acanthamoeba isolates from India with those of the United States. METHODS: Acanthamoeba isolates were obtained from corneal scrapings of 43 patients with infectious keratitis seen at the Francis I. Proctor Foundation (N = 23) and Aravind Eye Hospital (N = 20) from 2008 through 2012 and plated on growth media. A previously described minimum cysticidal concentration (MCC) assay was performed by a single laboratory technician to assess susceptibility to 5 antiamoebic agents for all isolates. Testing was conducted in triplicate, with the median MCC chosen for analyses. RESULTS: The MCC (µg/mL) of polyhexamethylene biguanide was 6.25 [IQR 5.47-12.5] for Aravind isolates and 6.25 [IQR 6.25-9.375] for Proctor isolates ( P = 0.75), corresponding values were 6.25 [IQR 3.125-6.25] and 3.125 [IQR 3.125-9.375] for chlorhexidine ( P = 0.81), 2500 [IQR 2500-5000] and 5000 [IQR 1250-20,000] for voriconazole ( P = 0.25), 15.6 [IQR 15.6-39.0625] and 15.6 [IQR 15.6-31.25] for hexamidine ( P = 0.92), and 15.6 [IQR 7.81-15.6] and 15.6 [IQR 7.81-31.25] for propamidine ( P = 0.42). CONCLUSIONS: This study found no statistically significant differences in antiamoebic susceptibility of Indian versus US samples from Acanthamoeba keratitis clinical isolates. These findings suggest that differences in antiamoebic susceptibility are likely not responsible for differential outcomes in Acanthamoeba keratitis between the 2 locations.
Assuntos
Ceratite por Acanthamoeba , Acanthamoeba , Humanos , Ceratite por Acanthamoeba/tratamento farmacológico , Clorexidina/farmacologia , Voriconazol/farmacologia , CaliforniaRESUMO
BACKGROUND: For bacterial infections, the susceptibility to antibiotics in vitro has been associated with clinical outcomes in vivo, although the importance of minimum inhibitory concentration (MIC) has been debated. In this study, we analyzed the association of MIC on clinical outcomes in bacterial corneal ulcers, while controlling for organism and severity of disease at presentation. METHODS: Data were collected as part of a National Eye Institute-funded, randomized, controlled trial (the Steroids for Corneal Ulcers Trial [SCUT]). All cases enrolled in SCUT had a culture-positive bacterial corneal ulcer and received moxifloxacin. The MIC to moxifloxacin was measured by E test. Outcomes included best spectacle-corrected visual acuity, infiltrate/scar size, time to re-epithelialization, and corneal perforation. RESULTS: Five hundred patients with corneal ulcers were enrolled in the trial, and 480 were included in this analysis. The most commonly isolated organisms were Streptococcus pneumoniae and Pseudomonas aeruginosa. A 2-fold increase in MIC was associated with an approximately 0.02 logMAR decrease in visual acuity at 3 weeks, approximately 1 letter of vision loss on a Snellen chart (0.019 logMAR; 95% confidence interval [CI], .0040-.033; P = .01). A 2-fold increase in MIC was associated with an approximately 0.04-mm larger infiltrate/scar size at 3 weeks (0.036 mm; 95% CI, .010-.061; P = .006). After controlling for organism, a higher MIC was associated with slower time to re-epithelialization (hazards ratio, 0.92; 95% CI, .86-.97; P = .005). CONCLUSIONS: In bacterial keratitis, a higher MIC to the treating antibiotic is significantly associated with worse clinical outcomes, with approximately 1 line of vision loss per 32-fold increase in MIC. CLINICAL TRIALS REGISTRATION: NCT00324168.
Assuntos
Antibacterianos/uso terapêutico , Compostos Aza/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Quinolinas/uso terapêutico , Antibacterianos/farmacologia , Compostos Aza/farmacologia , Bactérias/classificação , Bactérias/isolamento & purificação , Fluoroquinolonas , Humanos , Testes de Sensibilidade Microbiana , Moxifloxacina , Quinolinas/farmacologia , Resultado do TratamentoAssuntos
DNA de Protozoário/genética , DNA Viral/genética , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Virais/diagnóstico , Metagenômica/métodos , Análise de Sequência de DNA , Uveíte/diagnóstico , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/genética , Infecções Oculares Parasitárias/genética , Infecções Oculares Virais/genética , Herpes Simples/diagnóstico , Herpes Simples/genética , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/genética , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Humanos , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Simplexvirus/genética , Simplexvirus/isolamento & purificação , Toxoplasma/genética , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/genética , Uveíte/parasitologia , Uveíte/virologia , Corpo Vítreo/parasitologia , Corpo Vítreo/virologiaRESUMO
BACKGROUND: The chlamydial major outer membrane protein, encoded by the ompA gene, is a primary target for chlamydial vaccine research. However, human studies of ompA-specific immunity are limited, and prior studies have been limited in differentiating re-infection from persistent infection. The purpose of this study was to assess whether children living in trachoma-endemic communities with re-infections of ocular chlamydia were more likely to be infected with a different or similar genovar. METHODOLOGY AND FINDINGS: The study included 21 communities from a trachoma-hyperendemic area of Ethiopia that had been treated with a mass azithromycin distribution for trachoma. Conjunctival swabbing was offered to all children younger than 5 years of age at baseline (i.e., pre-treatment), and then at follow-up visits 2 and 6 months later. Swabs were subjected to polymerase chain reaction (PCR) to detect C. trachomatis. A random sample of 359 PCR-positive swabs, stratified by study visit and study community, was chosen for ompA sequencing. In addition, ompA sequencing was performed on all swabs of 24 children who experienced chlamydial re-infection (i.e., positive chlamydial test before treatment, negative test 2 months following mass distribution of azithromycin, and again a positive test 6 months post-treatment). ompA sequencing was successful for 351 of 359 swabs of the random sample and 44 of 48 swabs of the re-infection sample. In the random sample, ompA types clustered within households more than would be expected by chance. Among the 21 re-infected children with complete ompA data, 14 had the same ompA type before and after treatment. CONCLUSION: The high frequency of ompA concordance suggests incomplete genovar-specific protective immunity and the need for multiple antigens as vaccine targets.
Assuntos
Azitromicina , Tracoma , Azitromicina/uso terapêutico , Criança , Chlamydia trachomatis/genética , Túnica Conjuntiva , Humanos , Reação em Cadeia da Polimerase , Tracoma/tratamento farmacológico , Tracoma/epidemiologia , Tracoma/prevenção & controleRESUMO
Purpose: Acanthamoeba keratitis often is refractory to medical and surgical therapy, primarily because of the remarkable resilience of Acanthamoeba cysts. In this study, we directly compared the cysticidal activity and potency of several candidate medical therapies in vitro. Design: Experimental study. Participants: In vitro Acanthamoeba specimens obtained from 9 patients with keratitis seen at the Francis I. Proctor Foundation from 2008 through 2012. Methods: The minimum cysticidal concentration (MCC) of povidone iodine, natamycin, and chlorhexidine was investigated using an established assay technique. The relative potency of each agent was estimated starting with concentrations commonly used in clinical practice and determining the number of two-fold dilutions required to reach the MCC. Statistical comparisons of relative potency were performed using bootstrap simulations and permutation tests. Main Outcome Measures: Minimum cysticidal concentration and the number of two-fold dilutions required to reach the MCC. Results: The MCC for chlorhexidine ranged from 3.1 to 25 µg/ml (median, 12.5 µg/ml; interquartile range [IQR], 6.25-12.5 µg/ml), the MCC for natamycin ranged from 390.6 to 3125 µg/ml (median, 390.6 µg/ml; IQR, 390.6-781.2 µg/ml), and the MCC for povidone iodine ranged from 0.3 to 78.1 µg/ml (median, 2.4 µg/ml; IQR, 0.6-9.8 µg/ml). Doses commonly used in clinical practice (povidone iodine 1%, natamycin 5%, and chlorhexidine 0.04%) were approximately 12, 7, and 5 two-fold dilutions higher than the drug's corresponding median MCC, respectively (P < 0.001, comparing 3 drugs). Povidone iodine 1% had the highest potency of the 3 medications tested, requiring more dilutions than natamycin 5% (P < 0.001) and chlorhexidine 0.04% (P < 0.001) to reach the MCC. Conclusions: All 3 medications demonstrated in vitro cysticidal activity in each of the 9 isolates. The potency of 1% povidone iodine was greater than standard formulations of natamycin or chlorhexidine. Although its clinical efficacy is yet to be determined, povidone iodine may be considered as a potential adjuvant treatment in cases of recalcitrant Acanthamoeba keratitis.
RESUMO
After 6 biannual mass distributions of oral azithromycin for trachoma in Ethiopian communities, 76.8% (95% confidence interval [CI], 66.3%-85.1%) of nasopharyngeal Streptococcus pneumoniae isolates from children aged 1-5 years were resistant to macrolides. Twelve and 24 months after the last azithromycin treatment, resistance decreased to 30.6% (95% CI, 18.8%-40.4%; P <.001 ) and 20.8% (95% CI, 12.7%-30.7%; P < .001), respectively. Macrolide resistance decreases after antibiotic pressure is removed.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Tracoma/prevenção & controle , Pré-Escolar , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/epidemiologia , Tracoma/epidemiologia , Tracoma/microbiologiaRESUMO
BACKGROUND: It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. METHODS AND FINDINGS: In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p < 0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. CONCLUSIONS: This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00322972. Please see later in the article for the Editors' Summary.
Assuntos
Antibacterianos/uso terapêutico , Macrolídeos/uso terapêutico , Nasofaringe/microbiologia , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/fisiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Lactente , MasculinoRESUMO
Increasing antibiotic consumption has been shown to lead to increased antibiotic resistance selection. We evaluated the prevalence of antibiotic resistance in Streptococcus pneumoniae to commonly used antibiotic classes as well as correlations between resistance and antibiotic consumption at the individual and community levels in children aged 0-59 months in Nouna district, Burkina Faso. A population-based sample of 300 children aged 0-59 months was randomly selected from the most recent census in 18 communities in the Nouna Health and Demographic Surveillance Site. Caregivers were interviewed about children's recent antibiotic use, and a nasopharyngeal swab was collected from each child. Nasopharyngeal swabs were processed using standard microbiological methods to determine pneumococcal carriage and resistance. Community-level antibiotic consumption was determined by record review from primary healthcare facilities, which routinely collect prescription data for children aged 0-59 months. Streptococcus pneumoniae was isolated from 101 (35.7%) nasopharyngeal samples. Among positive isolates, co-trimoxazole (75.6%) and tetracycline (69.3%) resistance was the most common, followed by oxacillin (26.7%) and azithromycin (9.9%). Recent antibiotic use was associated with decreased pneumococcal carriage (odds ratio 0.56, 95% CI: 0.33-0.93) at the individual level. There was no statistically significant relationship between antibiotic use and antibiotic resistance at the individual or community levels, although CIs were generally wide. The prevalence of antibiotic resistance to commonly used antibiotics was high in the study area. Expanding antimicrobial resistance surveillance in areas with little population-based data will be important for informing policy related to antibiotic use.
Assuntos
Antibacterianos/uso terapêutico , Portador Sadio/microbiologia , Farmacorresistência Bacteriana/fisiologia , Streptococcus pneumoniae/fisiologia , Azitromicina , Burkina Faso/epidemiologia , Portador Sadio/epidemiologia , Pré-Escolar , Clindamicina , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Nasofaringe/microbiologia , Oxacilina , Fatores de Risco , Streptococcus pneumoniae/isolamento & purificação , Tetraciclina , Resistência a Tetraciclina/fisiologia , Combinação Trimetoprima e SulfametoxazolRESUMO
BACKGROUND: Mass azithromycin distributions are effective for clearing ocular strains of Chlamydia trachomatis, yet infection frequently returns in areas with hyperendemic trachoma. A better understanding of the factors associated with chlamydial reinfection could be helpful to plan trachoma elimination strategies. METHODS: This was a prospective cohort study conducted in a trachoma-hyperendemic region of Ethiopia in 2003. As part of a larger cluster-randomized trial, 21 villages were treated with a single mass azithromycin distribution and all children 5 years and younger were monitored for ocular chlamydia and clinically active trachoma at baseline and at 2 and 6 months following the treatment. RESULTS: In 20 villages with available data, azithromycin treatment coverage was 88.7% (95% confidence interval [CI] 85.7-91.8%). In total, 1005 children tested negative for ocular chlamydia at the 2-month visit, of whom 41 became infected by 6 months (1.0 incident chlamydia infections per 100 person-months, 95%CI 0.7-1.4). The presence of intense trachomatous inflammation (TI) at baseline was associated with incident infection at 6 months (incidence rate ratio 1.91, 95%CI 1.03-3.55). Ocular chlamydia infections clustered more within households than communities: (intraclass correlation coefficient 0.01 for communities and 0.29 for households six months posttreatment). Younger children were more likely to have persistent clinically active trachoma (P = 0.03). CONCLUSIONS: More intensive antibiotic distributions may be warranted for younger children, for children with TI, and for households containing children with ocular chlamydia infections.
Assuntos
Antibioticoprofilaxia/métodos , Azitromicina/uso terapêutico , Chlamydia trachomatis/isolamento & purificação , Infecções Oculares Bacterianas/tratamento farmacológico , População Rural/estatística & dados numéricos , Tracoma/tratamento farmacológico , Antibacterianos/uso terapêutico , Pré-Escolar , Etiópia/epidemiologia , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Masculino , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Tracoma/epidemiologia , Tracoma/microbiologiaRESUMO
PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 µg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%-78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%-50.3%) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.
Assuntos
Ceratite por Acanthamoeba/tratamento farmacológico , Acanthamoeba/isolamento & purificação , Amebicidas/farmacologia , Infecções Oculares Parasitárias/tratamento farmacológico , Voriconazol/farmacologia , Acanthamoeba/efeitos dos fármacos , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/parasitologia , Animais , Antifúngicos/farmacologia , Sinergismo Farmacológico , Infecções Oculares Parasitárias/parasitologia , Humanos , Testes de Sensibilidade ParasitáriaRESUMO
CONTEXT: Treatment recommendations assume that repeated mass antibiotic distributions can control, but not eradicate or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued. OBJECTIVE: To determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization-recommended annual treatment. DESIGN, SETTING, AND PARTICIPANTS: A cluster-randomized clinical trial of biannual vs annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005. INTERVENTIONS: At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually. MAIN OUTCOME MEASURE: Village prevalence of ocular chlamydial infection and presence of elimination at 24 months in preschool children determined by polymerase chain reaction, correcting for baseline prevalence. Antibiotic treatments were performed after sample collections. RESULTS: Overall, 14,897 of 16,403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% (range, 14.7%-56.4%) to 6.8% (range, 0.0%-22.0%) at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment (range, 6.1%-48.6%) to 0.9% (range, 0.0%-4.8%) at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P = .03, adjusting for baseline prevalence). At 24 months, no infection could be identified in 6 of 8 of those treated biannually and in 1 of 8 of those treated annually (P = .049, adjusting for baseline prevalence). CONCLUSION: Local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00221364.
Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Tracoma/tratamento farmacológico , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
PURPOSE: Understanding the spectrum of pathogens in a given geographic region is important when deciding on empiric antibiotic therapy. In this study, we evaluate the spectrum of bacterial organisms cultured from corneal samples and their antibiotic sensitivities to guide initial treatment of keratitis. METHODS: We performed a retrospective case review of cultures from suspected infectious keratitis cases at the Francis I. Proctor Foundation, University of California, San Francisco, from 1996 through 2015. Logistic regression models were used to assess the risk of culturing methicillin-resistant Staphylococcus aureus (MRSA) from ulcers over time and the association between the year cultured and moxifloxacin resistance. RESULTS: A total of 522 of 2203 (23.7%) cultures grew bacterial organisms believed to be the etiology of infection, with available antibiotic sensitivity data. Of these, 338 (65.3%) grew gram-positive organisms with the most common being methicillin-sensitive Staphylococcus aureus (20.1%, N = 105). One hundred eighty (34.7%) grew gram-negative species with Pseudomonas aeruginosa as the most prevalent organism (10.9%, N = 57). There was 1.13 increased odds of culturing MRSA for each 1-year increase in the culture date (P = 0.01) and 1.26 increased odds of culturing an organism resistant to moxifloxacin with each 1-year increase in the culture date after controlling for the infectious organism (P < 0.001). CONCLUSIONS: Gram-positive organisms are the most commonly identified etiology of microbial keratitis in this series. Approximately 35% of cultured organisms had variable susceptibility to moxifloxacin, and resistance seems to be increasing over time. The risk of culturing MRSA increased over time.
Assuntos
Úlcera da Córnea/microbiologia , Farmacorresistência Bacteriana , Infecções Oculares Bacterianas/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Centros Médicos Acadêmicos , Antibacterianos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , São FranciscoRESUMO
There are various approaches to control trachoma. These include the elimination of the ocular strains of Chlamydia trachomatis that cause the disease and to decrease the spread of infection by other measures such as fly control. Here, we examined how these two are related (i.e., how treating children with antibiotics affects carriage of Chlamydia by flies). Flies were collected in villages that had received mass oral azithromycin distribution and were compared with flies in untreated villages. Polymerase chain reaction (PCR) was performed to detect chlamydial DNA on the flies. Conjunctival swabs were also taken to assay for chlamydial prevalence in the children. Chlamydia was found on 23% of the flies in the untreated villages but only 0.3% in treated villages. Prevalence of trachoma in children proved to be an excellent predictor of the prevalence on flies (correlation coefficient, 0.89). Thus, treating children with antibiotics may drastically reduce the role of flies as a vector.
Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Chlamydia/isolamento & purificação , Dípteros/microbiologia , Tracoma/prevenção & controle , Animais , DNA Bacteriano/isolamento & purificação , Etiópia/epidemiologia , Humanos , Lactente , Prevalência , População Rural , Tracoma/epidemiologiaRESUMO
PURPOSE: To compare the clinical features and antibiotic susceptibility of ocular methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). DESIGN: Cross-sectional study. METHODS: The Proctor clinical laboratory database was reviewed to identify all ocular isolates of S. aureus collected between July 1, 1998 and July 31, 2006. RESULTS: Of 915 S. aureus isolates, there were 88 MRSA isolates in 41 different patients. The proportion MRSA increased from 4.1% in 1998 to 1999 to 16.7% in 2005 to 2006. A total of 78.0% of patients with MRSA had blepharoconjunctivitis, 2.4% had cellulitis, 2.4% had dacryocystitis, 14.6% had keratitis, and 2.4% had endophthalmitis. The diagnoses associated with MSSA were not statistically different. A total of 63.6% of MRSA isolates were sensitive to bacitracin, 100% to vancomycin, 14.8% to ciprofloxacin, 14.8% to erythromycin, 97.7% to sulfisoxazole, and 93.2% to tetracycline. CONCLUSIONS: MRSA has become a more common ocular pathogen but, as with MSSA, causes mild disease. MRSA should be treated with vancomycin.
Assuntos
Antibacterianos/uso terapêutico , Infecções Oculares Bacterianas/microbiologia , Resistência a Meticilina , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Blefarite/microbiologia , California/epidemiologia , Conjuntivite/microbiologia , Estudos Transversais , Dacriocistite/microbiologia , Endoftalmite/microbiologia , Humanos , Ceratite/microbiologia , Meticilina/uso terapêutico , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Retrospectivos , Staphylococcus aureus/efeitos dos fármacosRESUMO
AIMS: To report trends in antibiotic resistance in cases of bacterial keratitis from a large eye hospital in South India. METHODS: In this retrospective cross-sectional study, the microbiology laboratory records of patients with infectious keratitis diagnosed at an eye hospital in South India from 2002 to 2013 were reviewed to determine the proportion with antibiotic non-susceptibility. RESULTS: 3685 bacterial isolates had susceptibility testing performed over the 12-year period. The two most common organisms with resistance were Streptococcus pneumoniae (n=1204) and Pseudomonas aeruginosa (n=894). Antibiotic non-susceptibility was generally uncommon for these two organisms and no significant trends were detected over the course of the study. In contrast, Staphylococcus aureus (N=211) isolates demonstrated a significant increase in fluoroquinolone non-susceptibility over the 12-year study period. This coincided with a significant increase in methicillin-resistant S. aureus (MRSA) during the study period, though the increase in fluoroquinolone resistance was likewise seen in methicillin-sensitive S. aureus (MSSA). For example, ofloxacin resistance in MSSA increased from 11.1% in 2002 to 66.7% in 2013 (p=0.002). No trends were apparent for the aminoglycosides, cefazolin or vancomycin, for which in vitro non-susceptibility generally appeared to be low. CONCLUSION: Resistance to antibiotics was generally stable for infectious keratitis isolates from a large eye hospital in South India, except for S. aureus, which experienced a significant increase in fluoroquinolone resistance from 2002 to 2013. Fluoroquinolone antibiotics currently have poor in vitro activity against both MRSA and MSSA in South India and are therefore not the ideal therapy for Staphylococcal corneal ulcers.