Correlates of multi-drug non-susceptibility in enteric bacteria isolated from Kenyan children with acute diarrhea.

Reduced antimicrobial susceptibility threatens treatment efficacy in sub-Saharan Africa, where data on the burden and correlates of antibiotic resistance among enteric pathogens are limited.Fecal samples from children aged 6 mos-15 yrs presenting with acute diarrhea in western Kenya were cultured for bacterial pathogens. HIV-uninfected children with identified Shigella or Salmonella species or pathogenic Escherichia coli (EPEC, ETEC, EAEC or EIEC) were included in this cross-sectional sub-study. Non-susceptibility to ampicillin, ceftriaxone, ciprofloxacin, cotrimoxazole, and tetracycline was determined using MicroScan Walkaway40 Plus. Multivariable log-binomial regression was used to identify correlates of multi-drug non-susceptibility (MDNS, non-susceptibility to ≥ 3 of these antibiotics).Of 292 included children, median age was 22.5 mos. MDNS was identified in 62.5% of 318 isolates. Non-susceptibility to cotrimoxazole (92.8%), ampicillin (81.3%), and tetracycline (75.0%) was common. Young age (6-24 mos vs. 24-59 mos adjusted prevalence ratio [aPR] = 1.519 [95% confidence interval: 1.19, 1.91]), maternal HIV (aPR = 1.29 [1.01, 1.66]); and acute malnutrition (aPR = 1.28 [1.06, 1.55]) were associated with higher prevalence of MDNS, as were open defecation (aPR = 2.25 [1.13, 4.50]), household crowding (aPR = 1.29 [1.08, 1.53]) and infrequent caregiver hand-washing (aPR = 1.50 [1.15, 1.95]).Young age, HIV exposure, acute malnutrition and poor sanitation may increase risk of antibiotic non-susceptible enteric pathogen infections among children in Kenya

Non-susceptibility patterns of <i>Shigella</i> spp., <i>Salmonella</i> spp., and select <i>E</i>. <i>Coli</i> strains isolated from study participants all Salmonella spp., Shigella spp., EPEC, ETEC, and EIEC isolates were susceptible to ceftriaxone.

<p>All Salmonella spp., Shigella spp., and ETEC isolates were susceptible to ciprofloxacin.</p

Prevalence of multi-drug non-susceptibility (MDNS) by age group, stratified by pathogen.

<p>Prevalence of multi-drug non-susceptibility (MDNS) by age group, stratified by pathogen.</p

Correlates of multi-drug non-susceptibility (MDNS) in enteropathogens in Kenyan children 6 mos–15 yrs with acute diarrhea.

<p>Correlates of multi-drug non-susceptibility (MDNS) in enteropathogens in Kenyan children 6 mos–15 yrs with acute diarrhea.</p

Characteristics of children with and without multi-drug non-susceptible enteric infections.

<p>Characteristics of children with and without multi-drug non-susceptible enteric infections.</p

Specific pathogens identified in the 26 children who had more than one pathogen of interest identified in the same stool sample.

<p>Specific pathogens identified in the 26 children who had more than one pathogen of interest identified in the same stool sample.</p

Antimicrobial resistance of <i>Klebsiella pneumoniae</i> stool isolates circulating in Kenya

<div><p>We sought to determine the genetic and phenotypic antimicrobial resistance (AMR) profiles of commensal <i>Klebsiella</i> spp. circulating in Kenya by testing human stool isolates of 87 <i>K</i>. <i>pneumoniae</i> and three <i>K</i>. <i>oxytoca</i> collected at eight locations. Over one-third of the isolates were resistant to ≥3 categories of antimicrobials and were considered multidrug-resistant (MDR). We then compared the resistance phenotype to the presence/absence of 238 AMR genes determined by a broad-spectrum microarray and PCR. Forty-six genes/gene families were identified conferring resistance to β-lactams (<i>ampC</i>/<i>bla</i>_DHA, <i>bla</i>_CMY/LAT, <i>bla</i>_LEN-1, <i>bla</i>_OKP-A/OKP-B1, <i>bla</i>_OXA-1-like family, <i>bla</i>_OXY-1, <i>bla</i>_SHV, <i>bla</i>_TEM, <i>bla</i>_CTX-M-1 and <i>bla</i>_CTX-M-2 families), aminoglycosides (<i>aac(3)-III</i>, <i>aac(6)-Ib</i>, <i>aad</i>(A1/A2), <i>aad</i>(A4), <i>aph</i>(AI), <i>aph3/str</i>(A), <i>aph6/str</i>(B), and <i>rmtB</i>), macrolides (<i>mac</i>(A), <i>mac</i>(B), <i>mph</i>(A)<i>/mph</i>(K)), tetracyclines (<i>tet</i>(A), <i>tet</i>(B), <i>tet</i>(D), <i>tet</i>(G)), ansamycins (<i>arr</i>), phenicols (<i>catA1/cat4</i>, <i>floR</i>, <i>cmlA</i>, <i>cmr</i>), fluoroquinolones (<i>qnrS</i>), quaternary amines (<i>qacE</i>Δ<i>1</i>), streptothricin (<i>sat2</i>), sulfonamides (<i>sul1</i>, <i>sul2</i>, <i>sul3</i>), and diaminopyrimidines (<i>dfrA1</i>, <i>dfrA5</i>, <i>dfrA7</i>, <i>dfrA8</i>, <i>dfrA12</i>, <i>dfrA13/21/22/23</i> family, <i>dfrA14</i>, <i>dfrA15</i>, <i>dfrA16</i>, <i>dfrA17</i>). This is the first profile of genes conferring resistance to multiple categories of antimicrobial agents in western and central Kenya. The large number and wide variety of resistance genes detected suggest the presence of significant selective pressure. The presence of five or more resistance determinants in almost two-thirds of the isolates points to the need for more effective, targeted public health policies and infection control/prevention measures.</p></div

Summary of antimicrobial phenotypic susceptibility for diarrheal and control isolates.

<p>Summary of antimicrobial phenotypic susceptibility for diarrheal and control isolates.</p

Summary of AMR genes in the tested population.

<p>Summary of AMR genes in the tested population.</p

Metadata and phenotypic antimicrobial susceptibility for individual isolates.

<p>Metadata and phenotypic antimicrobial susceptibility for individual isolates.</p