Dataset Information

Emerging Resistance to Empiric Antimicrobial Regimens for Pediatric Bloodstream Infections in Malawi (1998-2017).

ABSTRACT:

Background

The adequacy of the World Health Organization's Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi.

Methods

We determined the change in the population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998-2017). AMR profiles were assessed by the disc diffusion method, and trends over time were evaluated.

Results

A total 89643 pediatric blood cultures were performed, and 10621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1000 persons in 2002 to 3.4 per 1000 persons in 2017. Over 2 decades, the resistance of Gram-negative pathogens to all empiric, first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (P < .001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (P < .001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (P < .001).

Conclusions

The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens' resistance to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly-expanding AMR in childhood BSI.

SUBMITTER: Iroh Tam PY

PROVIDER: S-EPMC6579959 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Emerging Resistance to Empiric Antimicrobial Regimens for Pediatric Bloodstream Infections in Malawi (1998-2017).

Iroh Tam Pui-Ying PY Musicha Patrick P Kawaza Kondwani K Cornick Jenifer J Denis Brigitte B Freyne Bridget B Everett Dean D Dube Queen Q French Neil N Feasey Nicholas N Heyderman Robert R

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190601 1

<h4>Background</h4>The adequacy of the World Health Organization's Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi.<h4>Methods</h4>We determined the change in the population-based incidence of BSI in children admitted ...[more]

PMID: 30277505

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Project description:BackgroundBacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance.MethodsIn this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time.FindingsBetween Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016.InterpretationThe rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting.FundingWellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).

Project description:BackgroundCommunity-onset bloodstream infection (CO-BSI) is associated with substantial morbidity and mortality. Knowledge of locally prevalent pathogens and antimicrobial susceptibility patterns can promptly guide appropriate empiric therapy and improve outcomes.ObjectivesWe sought to determine the epidemiology of CO-BSI, the blood culture positivity rate and the contamination rate. We also sought to establish appropriateness of current empiric antimicrobial therapy practices.MethodsWe retrospectively analyzed blood cultures taken from January 2015 to December 2019 at the emergency departments (EDs) of a tertiary-care academic hospital in South Africa using extracted laboratory data.ResultsThe overall positivity rate of blood cultures taken at the EDs was 15% (95% confidence interval [CI], 0.15-0.16) and the contamination rate was 7% (95% CI, 0.06-0.07). Gram-positive bacteria predominated in the pediatric cohort: neonates, 52 (54%) of 96; infants, 57 (52%) of 109; older children, 63 (61%) of 103. Methicillin-susceptible Staphylococcus aureus was the predominant pathogen among older children: 30 (35%) of 85. Escherichia coli was the most common pathogen isolated among adults and the elderly: 225 (21%) of 1,060 and 62 (29%) of 214, respectively. Among neonates, the susceptibility of E. coli and Klebsiella pneumoniae to the combination of ampicillin and gentamicin was 17 (68%) of 25. Among adults, the susceptibility of the 5 most common pathogens to amoxicillin-clavulanate was 426 (78%) of 546 and their susceptibility to ceftriaxone was 481 (85%) of 565 (P = .20). The prevalence of methicillin-resistant S. aureus, extended-spectrum β-lactamase-producing and carbapenem-resistant Enterobacterales were low among all age groups.ConclusionsReview of blood culture collection techniques is warranted to reduce the contamination rate. High rates of resistance to currently prescribed empiric antimicrobial agents for CO-BSI warrants a re-evaluation of local guidelines.

Project description:BackgroundOvercrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China.Study designThis retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission.ResultsWe identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045).ConclusionsEscherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

Project description:PurposeAlthough the biliary tract is a common source of invasive infections, the epidemiology of cholangitis- and cholecystitis-associated bloodstream infection (BSI) is not well defined. The objective of this study was to determine the incidence, clinical determinants, microbiology of biliary tract-associated BSI, and predicted adequacy of common empiric therapy regimens.MethodsAll biliary tract-associated BSI in Queensland during 2000-2019 were identified using state-wide data sources. Predicted adequacy of empiric antimicrobial therapy was determined according to microbiological susceptibility data.ResultsThere were 3,698 episodes of biliary tract-associated BSI occurred in 3,433 patients of which 2,147 (58.1%) episodes were due to cholangitis and 1,551 (41.9%) cholecystitis, for age- and sex-standardized incidence rates of 2.7, and 2.0 per 100,000 population, respectively. An increasing incidence of biliary tract-associated BSI was observed over the study that was attributable to an increase in cholangitis cases. There was a significant increased risk for biliary tract-associated BSI observed with advancing age and male sex. Patients with cholangitis were older, more likely to have healthcare associated infection, and have more comorbidities most notably liver disease and malignancies as compared to patients with cholecystitis. The distribution of infecting pathogens was significantly different with polymicrobial aetiologies more commonly observed with cholangitis (18.4% vs. 10.5%; p < 0.001). The combination of ampicillin/gentamicin/metronidazole was predicted to have the overall highest adequacy (96.1%), whereas amoxicillin/clavulanate had the lowest (77.0%). Amoxicillin/clavulanate (75.2% vs. 79.4%, p:0.03) and ceftriaxone/metronidazole (83.4% vs. 89.6%; p < 0.001) showed significantly inferior predicted adequacy for cholangitis as compared to cholecystitis.ConclusionsBloodstream infections related to cholecystitis and cholangitis exhibit different epidemiology, microbiology, and requirements for empiric therapy.

Dataset Information

Emerging Resistance to Empiric Antimicrobial Regimens for Pediatric Bloodstream Infections in Malawi (1998-2017).

Background

Methods

Results

Conclusions

Publications

Emerging Resistance to Empiric Antimicrobial Regimens for Pediatric Bloodstream Infections in Malawi (1998-2017).

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