Risk Factors for Colonization With Extended-Spectrum Cephalosporin-Resistant and Carbapenem-Resistant Enterobacterales Among Hospitalized Patients in Kenya: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The spread of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) represents a significant global public health threat. We identified putative risk factors for ESCrE and CRE colonization among patients in 1 urban and 3 rural hospitals in Kenya. METHODS: During a January 2019 and March 2020 cross-sectional study, stool samples were collected from randomized inpatients and tested for ESCrE and CRE. The Vitek2 instrument was used for isolate confirmation and antibiotic susceptibility testing, and least absolute shrinkage and selection operator (LASSO) regression models were used to identify colonization risk factors while varying antibiotic use measures. RESULTS: Most (76%) of the 840 enrolled participants received ≥1 antibiotic in the 14 days preceding their enrollment, primarily ceftriaxone (46%), metronidazole (28%), or benzylpenicillin-gentamycin (23%). For LASSO models that included ceftriaxone administration, ESCrE colonization odds were higher among patients hospitalized for ≥3 days (odds ratio, 2.32 [95% confidence interval, 1.6-3.37]; P < .001), intubated patients (1.73 [1.03-2.91]; P = .009), and persons living with human immunodeficiency virus (1.70 [1.03-2.8]; P = .029). CRE colonization odds were higher among patients receiving ceftriaxone (odds ratio, 2.23 [95% confidence interval, 1.14-4.38]; P = .025) and for every additional day of antibiotic use (1.08 [1.03-1.13]; P = .002). CONCLUSIONS: While CRE colonization was strongly associated with ceftriaxone use and duration of antibiotic use, the odds of ESCrE colonization increased with exposure to the hospital setting and invasive medical devices, which may reflect nosocomial transmission. These data suggest several areas where hospitals can intervene to prevent colonization among hospitalized patients, both through robust infection prevention and control practices and antibiotic stewardship programs.

Cholera Outbreak in Dadaab Refugee Camp, Kenya - November 2015-June 2016.

Dadaab Refugee camp in Garissa County, Kenya, hosts nearly 340,000 refugees in five subcamps (Dagahaley, Hagadera, Ifo, Ifo2, and Kambioos) (1). On November 18 and 19, 2015, during an ongoing national cholera outbreak (2), two camp residents were evaluated for acute watery diarrhea (three or more stools in ≤24 hours); Vibrio cholerae serogroup O1 serotype Ogawa was isolated from stool specimens collected from both patients. Within 1 week of the report of index cases, an additional 45 cases of acute watery diarrhea were reported. The United Nations High Commissioner for Refugees and their health-sector partners coordinated the cholera response, community outreach and water, sanitation, and hygiene (WASH) activities; Médecins Sans Frontiéres and the International Rescue Committee were involved in management of cholera treatment centers; CDC performed laboratory confirmation of cases and undertook GIS mapping and postoutbreak response assessment; and the Garissa County Government and the Kenya Ministry of Health conducted a case-control study. To prevent future cholera outbreaks, improvements to WASH and enhanced disease surveillance systems in Dadaab camp and the surrounding area are needed.

Long-term antibiotic exposure landscapes and resistant Escherichia coli colonization in a densely populated setting.

Antibiotic exposure is associated with resistant bacterial colonization, but this relationship can be obscured in community settings owing to horizontal bacterial transmission and broad distributions. Locality-level exposure estimates considering inhabitants' length of stay, exposure history, and exposure conditions of areas nearby could clarify these relationships. We used prescription data filled during 2010-2015 for 23 antibiotic types for members of georeferenced households in a population-based infectious disease surveillance platform. For each antibiotic and locality, we generated exposure estimates, expressed in defined daily doses (DDD) per 1000 inhabitant days of observation (IDO). We also estimated relevant environmental parameters, such as the distance of each locality to water, sanitation, and other amenities. We used data on ampicillin, ceftazidime, and trimethoprim-and-sulfamethoxazole resistant Escherichia coli colonization from stool cultures of asymptomatic individuals in randomly selected households. We tested exposure-colonization associations using permutation analysis of variance and logistic generalized linear mixed-effect models. Overall, exposure was highest for trimethoprim-sulfamethoxazole (1.8 DDD per 1000 IDO), followed by amoxicillin (0.7 DDD per 1000 IDO). Of 1,386 unique household samples from 195 locations tested between September 2015 and January 2016, 90%, 85% and 4% were colonized with E. coli resistant to trimethoprim and sulfamethoxazole, ampicillin, and ceftazidime, respectively. Ceftazidime-resistant E. coli colonization was common in areas with increased trimethoprim-sulfamethoxazole, cloxacillin, and erythromycin exposure. No association with any of the physical environmental variables was observed. We did not detect relationships between distribution patterns of ampicillin or trimethoprim-and-sulfamethoxazole resistant E. coli colonization and the risk factors assessed. Appropriate temporal and spatial scaling of raw antibiotic exposure data to account for evolution and ecological contexts of antibiotic resistance could clarify exposure-colonization relationships in community settings and inform community stewardship program.

Nasal Carriage of Methicillin-Resistant Staphylococcus Sciuri Group by Residents of an Urban Informal Settlement in Kenya.

Background: The Staphylococcus sciuri group constitutes animal-associated bacteria but can comprise up to 4% of coagulase-negative staphylococci isolated from human clinical samples. They are reservoirs of resistance genes that are transferable to Staphylococcus aureus but their distribution in communities in sub-Saharan Africa is unknown despite the clinical importance of methicillin-resistant S. aureus. Objectives: We characterised methicillin-resistant S. sciuri group isolates from nasal swabs of presumably healthy people living in an informal settlement in Nairobi to identify their resistance patterns, and carriage of two methicillin resistance genes. Method: Presumptive methicillin-resistant S. sciuri group were isolated from HardyCHROM™ methicillin-resistant S. aureus media. Isolate identification and antibiotic susceptibility testing were done using the VITEK®2 Compact. DNA was extracted using the ISOLATE II genomic kit and polymerase chain reaction used to detect mecA and mecC genes. Results: Of 37 presumptive isolates, 43% (16/37) were methicillin-resistant including - S. sciuri (50%; 8/16), S. lentus (31%; 5/16) and S. vitulinus (19%; 3/16). All isolates were susceptible to ciprofloxacin, gentamycin, levofloxacin, moxifloxacin, nitrofurantoin and tigecycline. Resistance was observed to clindamycin (63%), tetracycline (56%), erythromycin (56%), sulfamethoxazole/trimethoprim (25%), daptomycin (19%), rifampicin (13%), doxycycline, linezolid, and vancomycin (each 6%). Most isolates (88%; 14/16) were resistant to at least 2 antibiotic combinations, including methicillin. The mecA and mecC genes were identified in 75% and 50% of isolates, respectively. Conclusion: Colonizing S. sciuri group bacteria can carry resistance to methicillin and other therapeutic antibiotics. This highlights their potential to facilitate antimicrobial resistance transmission in community and hospital settings. Surveillance for emerging multidrug resistant strains should be considered in high transmission settings where human-animal interactions are prevalent. Our study scope precluded identifying other molecular determinants for all the observed resistance phenotypes. Larger studies that address the prevalence and risk factors for colonization with S. sciuri group and adopt a one health approach can complement the surveillance efforts.

Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.

Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting.

Prevalence of colonization with multidrug-resistant bacteria in communities and hospitals in Kenya.

We estimated the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and methicillin-resistant Staphylococcus aureus (MRSA) in communities and hospitals in Kenya to identify human colonization with multidrug-resistant bacteria. Nasal and fecal specimen were collected from inpatients and community residents in Nairobi (urban) and Siaya (rural) counties. Swabs were plated on chromogenic agar to presumptively identify ESCrE, CRE and MRSA isolates. Confirmatory identification and antibiotic susceptibility testing were done using the VITEK®2 instrument. A total of 1999 community residents and 1023 inpatients were enrolled between January 2019 and March 2020. ESCrE colonization was higher in urban than rural communities (52 vs. 45%; P = 0.013) and in urban than rural hospitals (70 vs. 63%; P = 0.032). Overall, ESCrE colonization was ~ 18% higher in hospitals than in corresponding communities. CRE colonization was higher in hospital than community settings (rural: 7 vs. 1%; urban: 17 vs. 1%; with non-overlapping 95% confidence intervals), while MRSA was rarely detected (≤ 3% overall). Human colonization with ESCrE and CRE was common, particularly in hospitals and urban settings. MRSA colonization was uncommon. Evaluation of risk factors and genetic mechanisms of resistance can guide prevention and control efforts tailored to different environments.