Antibiotic resistance patterns of Escherichia coli in migrants vs non-migrants: a study of 14 561 urine samples.

BACKGROUND: To investigate the distribution of urine isolates and antibiotic resistance patterns in the predominant uropathogen Escherichia coli in migrant and non-migrant individuals. METHODS: We linked a cohort consisting of all migrants obtaining residence as refugees or family-reunited migrants in Denmark between January 1993 and December 2015 to hospital urine samples examined from January 2000 to December 2015 at the Department of Microbiology, University Hospital Hvidovre, Denmark. Samples from non-migrant individuals, Danish-born from Danish parents, were included as comparison. Analysis was carried out using multivariate logistic regression. RESULTS: There were 14 561 first-time urine samples included, with E. coli being the most prevalent bacterial pathogen. Of the identified isolates, 4686/11 737 were E. coli among non-migrants and 1032/2824 among migrants.Sulfamethoxazol-Trimethoprim (SXT) resistance was found in 34.3% (350/1020) of E. coli isolates among migrants and 23.2% (1070/4619) among non-migrant patients [odds ratio (OR) 1.73, 95% confidence interval (CI): 1.47-2.03]. Ciprofloxacin resistance was found in 5.8% (36/618) of isolates among migrants and 2.2% (67/3092) among non-migrants (OR 2.20, 95% CI: 1.37-3.53). Gentamicin (GEN) resistance was seen in 10.8% (61/565) and 4.7% (110/2328) of isolates (OR 2.33, 95% CI:1.63-3.34), Cefuroxime resistance in 8.5% (87/1019) and 3.4% (158/4618) (OR 2.40, 95% CI:1.77-3.24), Ampicillin (AMP) resistance in 51.4% and 40.8% (OR 1.65, 95% CI: 1.42-1.92) and Piperacillin-Tazobactam resistance in 6.9% (30/432) and 4.2% (65/1532) for migrant and non-migrant patients, respectively. When stratifying according to migrant status, family-reunited had higher odds of resistance than refugees for SXT, GEN and AMP. CONCLUSIONS: Prevalence of antibiotic resistance was significantly higher in E. coli isolates among migrants, both refugees and family-reunited, than non-migrant patients. Differences could not be explained by comorbidity or income. The results emphasize the importance of urine sample testing in both local-born and migrants before antibiotic start-up and point to the benefit of considering migration to secure individual treatment and equal health outcomes.

Second-line anti-tuberculosis drug concentrations for susceptibility testing in the MODS assay.

Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool for rapid liquid culture and direct isoniazid and rifampicin drug susceptibility testing (DST). The objective of this study was to explore the potential for extending the MODS assay to rapid second-line DST and to identify critical concentrations of candidate drugs for prospective testing. Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised MODS protocols, with a range of titrations of antimicrobial drugs added. Critical concentrations were determined using a modified Kaplan-Meier survival curve analysis. Candidate critical concentrations were determined for capreomycin (10 µg·mL(-1)), ciprofloxacin (1.25 µg·mL(-1)), cycloserine (40 µg·mL(-1)), ethambutol (10 µg·mL(-1)), ethionamide (5 µg·mL(-1)), kanamycin (5 µg·mL(-1)), para-aminosalicylic acid (10 µg·mL(-1)) and streptomycin (10 µg·mL(-1)). No cut-off point was identified for the other second-line drugs or for pyrazinamide. At particular concentrations of some second-line TB drugs this novel Kaplan-Meier analysis clearly differentiated populations that were susceptible or resistant. These candidate critical concentrations should now be tested in a range of epidemiological settings to define the performance of direct, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity.

Prolonged infectiousness of tuberculosis patients in a directly observed therapy short-course program with standardized therapy.

BACKGROUND: Effective tuberculosis control is compromised by a lack of clarity about the timeframe of viable Mycobacterium tuberculosis shedding after treatment initiation under programmatic conditions. This study quantifies time to conversion from smear and culture positivity to negativity in unselected tuberculosis patients receiving standardized therapy in a directly observed therapy short-course (DOTS) program. METHODS: Longitudinal cohort study following up 93 adults initiating tuberculosis therapy in Lima, Peru. Baseline culture and drug susceptibility tests (DSTs) were performed using the MBBacT, proportion, and microscopic observation drug susceptibility (MODS) methods. Smear microscopy and MODS liquid culture were performed at baseline and weekly for 4 weeks then every other week for 26 weeks. RESULTS: Median conversion time from culture positivity to culture negativity of 38.5 days was unaffected by baseline smear status. Patients with fully susceptible tuberculosis had a median time to culture conversion of 37 days; 10% remained culture positive at day 60. Delayed culture conversion was associated with multidrug resistance, regardless of DST method used; non-multidrug resistance as defined by the proportion method and MODS (but not MBBacT) was also associated with delay. Persistent day 60 smear positivity yielded positive and negative predictive values of 67% and 92%, respectively, for detecting multidrug resistance. CONCLUSIONS: Smear and culture conversion in treated tuberculosis patients takes longer than is conventionally believed, even with fully susceptible disease, and must be accounted for in tuberculosis treatment and prevention programs. Persistent day 60 smear positivity is a poor predictor of multidrug resistance. The industrialized-world convention of universal baseline DST for tuberculosis patients should become the standard of care in multidrug resistance-affected resource-limited settings.

Microscopic observation drug susceptibility assay for tuberculosis screening before isoniazid preventive therapy in HIV-infected persons.

BACKGROUND: Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. METHODS: A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. RESULTS: Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity. CONCLUSIONS: MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.

Analysis of matrix metalloproteinase secretion by macrophages.

Matrix metalloproteinases (MMPs) are zinc-dependent proteases whose physiological roles include control of leukocyte migration. They are implicated in tissue destruction in inflammatory and infectious diseases. MMPs are not only capable of degrading all components of the extracellular matrix, but they also can modulate the immune response by cleaving cytokines and chemokines to alter their activity. Macrophages secrete a broad range of MMPs and represent a key source of MMPs in inflammatory lesions such as granulomas. Zymography is substrate-based gel electrophoresis that allows direct visualization of MMP activity. Here we describe measurement of MMP secretion from macrophages focusing on quantitative zymography. We also discuss complementary methods that should be used in parallel with zymography. The ability to analyze and quantify MMP secretion by macrophages offers an additional window through which to understand the contributions of macrophages to a wide variety of infectious, inflammatory, and immunologic disorders.

Impact on and use of an inner-city London Infectious Diseases Department by international migrants: a questionnaire survey.

BACKGROUND: The UK has witnessed a considerable increase in immigration in the past decade. Migrant may face barriers to accessing appropriate health care on arrival and the current focus on screening certain migrants for tuberculosis on arrival is considered inadequate. We assessed the implications for an inner-city London Infectious Diseases Department in a high migrant area. METHODS: We administered an anonymous 20-point questionnaire survey to all admitted patients during a 6 week period. Questions related to sociodemographic characteristics and clinical presentation. Analysis was by migration status (UK born vs overseas born). RESULTS: 111 of 133 patients completed the survey (response rate 83.4%). 58 (52.2%) were born in the UK; 53 (47.7%) of the cohort were overseas born. Overseas-born were over-represented in comparison to Census data for this survey site (47.7% vs 33.6%; proportional difference 0.142 [95% CI 0.049-0.235]; p = 0.002): overseas born reported 33 different countries of birth, most (73.6%) of whom arrived in the UK pre-1975 and self-reported their nationality as British. A smaller number (26.4%) were new migrants to the UK (< or =10 years), mostly refugees/asylum seekers. Overseas-born patients presented with a broad range and more severe spectrum of infections, differing from the UK-born population, resulting in two deaths in this group only. Presentation with a primary infection was associated with refugee/asylum status (n = 8; OR 6.35 [95% CI 1.28-31.50]; p = 0.023), being a new migrant (12; 10.62 [2.24-50.23]; p = 0.003), and being overseas born (31; 3.69 [1.67-8.18]; p = 0.001). Not having registered with a primary-care physician was associated with being overseas born, being a refugee/asylum seeker, being a new migrant, not having English as a first language, and being in the UK for < or =5 years. No significant differences were found between groups in terms of duration of illness prior to presentation or duration of hospitalisation (mean 11.74 days [SD 12.69]). CONCLUSION: Migrants presented with a range of more severe infections, which suggests they face barriers to accessing appropriate health care and screening both on arrival and once settled through primary care services. A more organised and holistic approach to migrant health care is required.

Zinc cream and reliability of tuberculosis skin testing.

In 50 healthy Peruvian shantytown residents, zinc cream applied to tuberculosis skin-test sites caused a 32% increase in induration compared with placebo cream. Persons with lower plasma zinc had smaller skin-test reactions and greater augmentation with zinc cream. Zinc deficiency caused false-negative skin-test results, and topical zinc supplementation augmented antimycobacterial immune responses enough to improve diagnosis.

Does traditional medicine use hamper efforts at tuberculosis control in urban Peru?

Decades of social and political unrest have contributed to the urbanization of the population of Peru with large-scale migration from rural Andean and Amazonian communities to overcrowded shantytowns around Lima. We administered a face-to-face survey questionnaire to 116 patients with suspected and proven tuberculosis (TB) in northern Lima to determine the extent to which the use of traditional therapies from indigenous regions persists and the impact of any such use on TB control. Sixty-three percent of participants reported some form of self-treatment prior to presentation to the National Tuberculosis Program; 52% of them used traditional remedies. Symptom duration was longer among self-remedy users than non-users (median = 25 versus 15 days; P = 0.07) and among those exclusively using western remedies rather than traditional remedies (median = 30 versus 15 days; P = 0.01). We thus found no evidence that use of traditional remedies has an appreciable effect on diagnostic delay in Lima.