The Clinical Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines are the most popular breakpoint guidelines used in ...antimicrobial susceptibility testing worldwide. The EUCAST guidelines are freely available to users while CLSI is available for non-members as a package of three documents for US $500 annually. This is prohibitive for clinical microbiology laboratories in resource poor settings. We set out to compare antibiotic susceptibility determined by the two guidelines to determine whether adoption of EUCAST guidelines would significantly affect our susceptibility patterns.
We reviewed minimum inhibitory concentrations (MIC) of various antibiotics routinely reported for Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) isolates from an automated microbiology identification system (VITEK-2) at the Aga Khan University Hospital Nairobi's Pathology department. These MICs were then analyzed using both CLSI 2015 and EUCAST 2015 guidelines and classified as resistant, intermediate or susceptible. We compared the susceptibility and agreement between the CLSI and EUCAST categorizations.
Susceptibility data from a total of 5165 E. coli, 1103 S. aureus and 532 P. aeruginosa isolates were included. The concordance rates of the two guidelines for E. coli, S. aureus and P. aeruginosa ranged from 78.2 to 100 %, 94.6 to 100 % and 89.1 to 95.5 % respectively. The kappa statistics for E. coli MICs revealed perfect agreement between CLSI and EUCAST for cefotaxime, ceftriaxone and trimethoprim-sulfamethoxazole, almost perfect agreement for ampicillin, ciprofloxacin, cefuroxime, gentamicin and ceftazidime, substantial agreement for meropenem, moderate agreement for cefepime and amoxicillin-clavulanate, fair agreement for nitrofurantoin and poor agreement for amikacin. For S. aureus the kappa statistics revealed perfect agreement for penicillin, trimethoprim-sulfamethoxazole, levofloxacin, oxacillin, linezolid and vancomycin, almost perfect agreement for clindamycin, erythromycin and tetracycline and moderate agreement for gentamicin. For P. aeruginosa the kappa analysis revealed moderate to almost perfect agreement for all the anti-pseudomonal antibiotics.
The results show comparable antibiotic susceptibility patterns between CLSI and EUCAST breakpoints. Given that EUCAST guidelines are freely available, it makes it easier for laboratories in resource poor settings to have an updated and readily available reference for interpreting antibiotic susceptibilities.
has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela ...revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description,
has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304
isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure.
isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in
as the most widespread mutation associated with azole resistance and S639P in
for echinocandin resistance. Copy number variants in
predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in
In less than a decade,
has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other
species,
is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new
introductions. Through a global collaboration, we assessed genome evolution of isolates of
from 19 countries. Here, we described estimated timing of the expansion of each
clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.
MALDI-TOF MS is an analytical method that has recently become integral in the identification of microorganisms in clinical laboratories. It relies on databases that majorly employ pattern recognition ...or fingerprinting. Biomarker based databases have also been developed and there is optimism that these may be superior to pattern recognition based databases. This study compared the performance of ribosomal biomarker based MALDI-TOF MS and conventional methods in the identification of selected bacteria and yeast.
The study was a cross sectional study identifying clinically relevant bacteria and yeast isolated from varied clinical specimens submitted to a clinical laboratory. The identification of bacteria using conventional Vitek 2™ automated system, serotyping and MALDI-TOF MS was performed as per standard operating procedures. Comparison of sensitivities were then carried out using Pearson Chi-Square test and p-value of <0.05 was considered statistically significant. Secondary outcomes analyzed included the major and minor error rates.
Of the 383 isolates MALDI-TOF MS and conventional methods identified 97.6 and 95.7% (p = 0.231) to the genus level and 97.4 and 88.0% (p = 0.000) to the species level respectively. Biomarker based MALDI-TOF MS was significantly superior to Vitek 2™ in the identification of Gram negative bacteria and Gram positive bacteria to the species level. For the Gram positive bacteria, significant difference was observed in the identification of Coagulase negative Staphylococci (p = 0.000) and Enterococcus (p = 0.008). Significant difference was also observed between serotyping and MALDI-TOF MS (p = 0.005) and this was attributed to the lack of identification of Shigella species by MALDI-TOF MS. There was no significant difference observed in the identification of yeast however some species of Candida were unidentified by MALDI-TOF MS.
Biomarker based MALDI-TOF MS had good performance in a clinical laboratory setting with high sensitivities in the identification of clinically relevant microorganisms.
Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, ...especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data.
We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity and susceptibility data captured in hospital and laboratory electronic records between 2010 and 2014.
For blood isolates, we used culture collection within the first three days of hospitalization as a surrogate for community onset, and within that group, Escherichia coli was the most common, followed by Staphylococcus aureus. In contrast, Candida spp. and Klebsiella pneumoniae were the most common hospital onset causes of bloodstream infection. Antimicrobial resistance rates for the most commonly isolated Gram negative organisms was higher than many recent reports from Europe and North America. In contrast, Gram positive resistance rates were quite low, with 94% of S. aureus being susceptible to oxacillin and only rare isolates of vancomycin-resistant enterococci.
The current report demonstrates high rates of antimicrobial resistance in Gram negative organisms, even in outpatients with urinary tract infections. On the other hand, rates of resistance in Gram positive organisms, notably S. aureus, are remarkably low. A better understanding of the reasons for these trends may contribute to ongoing efforts to combat antimicrobial resistance globally.
Relevant seroprevalence data for endemic pathogens in a given region provide insight not only into a population's susceptibility to acute infection or risk for reactivation disease but also into the ...potential need for policy initiatives aimed at reducing these risks. Data from sub-Saharan Africa are sparse and since Aga Khan University Hospital Nairobi is an internationally accredited hospital equipped with a laboratory electronic medical record system, analysis of pertinent local seroprevalence data has been made possible.
We have analyzed serology data from laboratory electronic records at a 300 bed tertiary private teaching hospital in Kenya for the dates, 2008 to 2017 for Toxoplasma gondii, cytomegalovirus, and rubella, which were used primarily for antenatal screening. We also analyzed the data from hepatitis A and amebiasis serologies, which were used primarily for diagnostic purposes.
For T. gondii, cytomegalovirus, and rubella, we used IgG serology to determine seroprevalence, finding rates of 32%, 86%, and 89%, respectively. There was no significant age-related difference in the 20 to 49 year old age range for any of these three pathogens. Of the Hepatitis A IgM tests that were ordered, 33% were positive with a peak positive rate of 70% in the five to nine year old age range. The seroprevalence of amebiasis was 4% and all cases of seropositivity were accompanied by compatible clinical illness (hepatic abscess).
These data provide insight into seroprevalence rates of selected pathogens that can be used to guide screening and diagnostic laboratory testing as well as private and public immunization practices.
•Candida auris appeared and became the predominant Candida species in 2011.•C. auris candidemia is more associated with central venous catheterization than candidemia caused by Candida albicans.•C. ...auris is resistant in vitro to the azoles.•Even with drugs that are active in vitro, candidemia is difficult to clear.•C. auris candidemia patients are older and with prolonged hospitalization, but don’t have increased mortality.
Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia.
Patients with candidemia were identified by the electronic medical record and reviewed for risk factors and outcome. Candida isolates were identified by Vitek2 as Candida haemulonii, but species determinations for 21 of the isolates using published molecular and proteomic methods identified all as C. auris.
From September 2010 to December 2016, C. auris accounted for 38% of 201 patients with candidemia, while C. albicans contributed 25%. C. auris patients had been hospitalized longer (mean 32 days vs. 13 days; p<0.001), were more likely to have central lines preceding candidemia than C. albicans patients (84% vs. 54%; p=<0.001) and had more commonly been treated with carbapenems (83% vs 61% for C. albicans p=0.01). The crude mortality was 29%, compared to 36% for C. albicans.
These findings suggest an opportunistic pathogen that may be less virulent, but difficult to eradicate and that control efforts should focus on antimicrobial usage.
Staphylococcus aureus (S.aureus) is a major cause of both healthcare and community acquired infections. In developing countries, manual phenotypic tests are the mainstay for the identification of ...staphylococci with the tube and slide coagulase tests being relied upon as confirmatory tests for S. aureus. The subjectivity associated with interpretation of these tests may result in misidentification of coagulase negative staphylococci as S.aureus. Given that antibiotic resistance is more prevalent in CONS, this may result in over estimation of methicillin resistant S.aureus (MRSA) prevalence.
A review of susceptibility data from all non-duplicate S.aureus isolates generated between March 2011 and May 2013 by the Vitek-2 (bioMérieux) automated system was performed by the authors. The data was generated routinely from processed clinical specimens submitted to the microbiology laboratories for culture and sensitivity at the Aga Khan University Hospital and Gertrude's children's hospital both situated in Nairobi.
Antimicrobial susceptibility data from a total of 731 non-duplicate S.aureus isolates was reviewed. Majority (79.2%) of the isolates were from pus swabs. Only 24 isolates were both cefoxitin and oxacillin resistant while 3 were resistant to oxacillin but susceptible to cefoxitin giving an overall MRSA prevalence of 3.7% (27/731). None of the isolates were resistant to mupirocin, linezolid, tigecycline, teicoplanin or vancomycin.
The prevalence of MRSA in this study is much lower than what has been reported in most African countries. The significant change in antibiotic susceptibility compared to what has previously been reported in our hospital is most likely a consequence of the transition to an automated platform rather than a trend towards lower resistance rates.
Background
Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent ...challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.
Methods
An initial stakeholders’ forum was convened to brainstorm on the process for developing the curriculum and some issues deliberated upon include the design approach, development roadmap, curriculum outline and scope, delivery, and evaluation methodologies. A dedicated team of subject matter experts (SMEs), drawn from the project and government ministries, compiled the initial draft of the curriculum and later the training materials. A series of other stakeholders’ meetings were convened to review these materials. The National Antimicrobial Stewardship Interagency Committee (NASIC) of the MOH in Kenya identified a team of experts from academia, research, and government to work with the SMEs in reviewing and providing valuable inputs to the curriculum. Additionally, principles of adult learning and a One Health approach for development were considered as AMR has drivers and impacts across sectors. A validation workshop was held to finalize the documents with a formal launch conducted during the World Antibiotics Awareness Week of 2020.
Results
A multisectoral AMR surveillance training curriculum and facilitator and trainee manuals were developed and endorsed by MOH and Ministry of Agriculture, Livestock, Fisheries and Cooperatives within one year. Over 500 healthcare workers in 19 counties were trained, with overwhelming adoption by other stakeholders in Kenya and beyond.
Conclusion
This curriculum was developed to standardize training for AMR detection and surveillance. The central role played by the MOH ensured expeditious development and roll-out of this curriculum. The in-service curriculum, now available on an e-learning platform, provides a ready opportunity to build capacity of healthcare professionals. Additional resources are needed to standardize and scale these efforts to reach all healthcare workers.
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