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OBJECTIVE: Azithromycin is an alternative to treat invasive non-typhoidal Salmonella (iNTS) infections. We determined its epidemiological cut-off (ECOFF) and compared azithromycin susceptibility testing methods for iNTS. METHODS: We used EUCAST ECOFFinder to determine the minimum inhibitory concentrations (MIC; obtained by broth microdilution) ECOFF and corresponding disk zone diameters of 515 iNTS from blood cultures in Democratic Republic of Congo, Burkina Faso, Rwanda, and Cambodia. Transferable resistance mechanisms were determined by polymerase chain reaction. We compared azithromycin susceptibility testing by semi-automated broth microdilution (customized Sensititre panel; reference), agar dilution, gradient tests (bioMérieux, Liofilchem, HiMedia; read at 80% (MIC80%) and 100% inhibition (MIC100%)), and disk diffusion (Rosco, Oxoid, BD, Liofilchem) for 161 wild- and 198 non-wild-type iNTS. RESULTS: Azithromycin MIC ECOFF was 16 mg/L corresponding to a 12 mm zone diameter; mphA was detected in 192/197 non-wild- and 0/47 wild-type iNTS. Categorical agreement was excellent (≥98%) for all methods. Essential agreement was very good for agar dilution (>90%) but moderate for gradient tests (MIC80%: 52% to 71% and MIC100%: 72% to 91%). Repeatability was good for all methods/brands. Interreader agreement was high for broth microdilution and agar dilution (all ≤1 twofold dilution difference) and disk diffusion (>96% ≤3 mm difference) but lower for gradient tests (MIC80% & MIC100%: 83% to 94% ≤1 twofold dilution difference). DISCUSSION: Azithromycin ECOFF of iNTS was 16 mg/L, i.e. equal to Salmonella Typhi. Disk diffusion is an accurate, precise, and user-friendly alternative for agar dilution and broth microdilution. Reading gradient tests at 100% instead of 80% inhibition improved accuracy and precision. ispartof: CLINICAL MICROBIOLOGY AND INFECTION vol:28 issue:12 pages:1615-1623 ispartof: location:England status: published

Additional file 1: Table S1. Diagnostic ascertainment of the 12 (NIDIAG) target priority infections; Table S2. Case ascertainment of conditions not targeted by the NIDIAG workup; Table S3. STROBE Checklist of items for cross-sectional studies (NIDIAG); Table S4. STARD checklist NIDIAG study.

OBJECTIVES: Community-level antibiotic use contributes to antimicrobial resistance, but is rarely monitored as part of efforts to optimize antibiotic use in low- and middle-income countries (LMICs). We investigated antibiotic use in the 4 weeks before study inclusion for persistent fever. METHODS: The NIDIAG-Fever (Neglected Infectious diseases DIAGnosis-Fever) study investigated aetiologies of infections in patients ≥5 years old with fever ≥1 week in six healthcare facilities in Cambodia, the Democratic Republic of the Congo (DRC), Nepal, and Sudan. In the present nested cross-sectional study, we describe prevalence and choice of antibiotics before and at study inclusion, applying the Access/Watch/Reserve (AWaRe) classification of the WHO List of Essential Medicines. Factors associated with prior antibiotic use were analysed. RESULTS: Of 1939 participants, 428 (22.1%) reported the prior use of one or more antibiotics, ranging from 6.3% (24/382, Cambodia) to 35.5% (207/583, Nepal). Of 545 reported antibiotics, the most frequent were Watch group antibiotics (351/545, 64.4%), ranging from 23.6% (DRC) to 82.1% (Nepal). Parenteral administration ranged from 5.9% to 69.6% between study sites. Antibiotic use was most frequent among young patients (5-17 years of age; risk ratio 1.42, 95%CI 1.19-1.71) and men (RR 1.29; 95%CI 1.09-1.53). No association was found with specific symptoms. Of 555 antibiotics started before study inclusion, 275 (49.5%) were discontinued at study inclusion. CONCLUSIONS: Watch antibiotics were frequently used, and discontinued upon study inclusion. The antibiotic use frequency and choice varied importantly between LMICs. Data on local antibiotic use are essential to guide efforts to optimize antibiotic use in LMICs, should not be restricted to hospitals, and need to take local healthcare utilization into account. ispartof: CLINICAL MICROBIOLOGY AND INFECTION vol:27 issue:9 pages:1293-1300 ispartof: location:England status: published

Childhood vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in Cambodia in January 2015. Baseline data regarding circulating serotypes are scarce. All microbiology laboratories in Cambodia were contacted for identification of stored isolates offrom clinical specimens taken before the introduction of PCV13. Available isolates were serotyped using a multiplex polymerase chain reaction method. Among 166 identified isolates available for serotyping from patients with pneumococcal disease, 4% were isolated from upper respiratory samples and 80% were from lower respiratory samples, and 16% were invasive isolates. PCV13 serotypes accounted for 60% (95% confidence interval [CI] 52-67) of all isolates; 56% (95% CI 48-64) of noninvasive and 77% (95% CI 57-89) of invasive isolates. Antibiotic resistance was more common among PCV13 serotypes. This study of clinicalisolates supports the potential for high reduction in pneumococcal disease burden and may serve as baseline data for future monitoring ofserotypes circulation after implementation of PCV13 childhood vaccination in Cambodia. ispartof: American Journal of Tropical Medicine and Hygiene vol:98 issue:3 pages:791-796 ispartof: location:United States status: published

In resource-limited settings, the scarcity of skilled personnel and adequate laboratory facilities makes the differential diagnosis of fevers complex [1-5]. Febrile illnesses are diagnosed clinically in most rural centers, and both Rapid Diagnostic Tests (RDTs) and clinical algorithms can be valuable aids to health workers and facilitate therapeutic decisions [6,7]. The persistent fever syndrome targeted by NIDIAG is defined as presence of fever for at least one week. The NIDIAG clinical research consortium focused on potentially severe and treatable infections and therefore targeted the following conditions as differential diagnosis of persistent fever: visceral leishmaniasis (VL), human African trypanosomiasis (HAT), enteric (typhoid and paratyphoid) fever, brucellosis, melioidosis, leptospirosis, malaria, tuberculosis, amoebic liver abscess, relapsing fever, HIV/AIDS, rickettsiosis, and other infectious diseases (e.g., pneumonia). From January 2013 to October 2014, a prospective clinical phase III diagnostic accuracy study was conducted in one site in Cambodia, two sites in Nepal, two sites in Democratic Republic of the Congo (DRC), and one site in Sudan (clinicaltrials.gov no. NCT01766830). The study objectives were to (1) determine the prevalence of the target diseases in patients presenting with persistent fever, (2) assess the predictive value of clinical and first-line laboratory features, and (3) assess the diagnostic accuracy of several RDTs for the diagnosis of the different target conditions.

Whole-genome sequencing of the four isolates used in this study was supported by Wellcome Trust grant 098051, awarded to the Wellcome Trust Sanger Institute. This work was also supported by project grants from the Australian National Health and Medical Research Council and the Wellcome Trust. S.J.P. receives funding from the NIHR Cambridge Biomedical Research Centre. Burkholderia pseudomallei isolates with shared multilocus sequence types (STs) have not been isolated from different continents. We identified two STs shared between Australia and Cambodia. Whole-genome analysis revealed substantial diversity within STs, correctly identified the Asian or Australian origin, and confirmed that these shared STs were due to homoplasy. Publisher PDF

Objectives Community-acquired pneumonia (CAP) is one of the most important causes of morbidity and mortality worldwide. Etiological data for Cambodia is scarce. We aimed to describe the main etiological agents causing CAP, and their resistance patterns in Cambodia and the greater Mekong region. Methods A review of bacterial etiologies of CAP and antimicrobial resistance in Cambodia and neighboring countries was conducted via: (1) a systematic review of published literature in all NCBI databases using Pubmed, Google scholar, EMBASE, the World Health Organization and the Cambodian Ministry of Health libraries; (2) a review of unpublished data from Cambodia provided by national and international stakeholders working at different tiers of the healthcare system. Results Twenty three articles and five data sources reported etiologies for 5919 CAP patients diagnosed between May 1995 and December 2012, including 1421 (24.0%), 3571 (60.3%) and 927 (15.7%) from Cambodia, Thailand and Vietnam, respectively. Streptococcus pneumoniae and Haemophilus influenzae were the most common pathogens ranking among the five most prevalent in 12 and 10 studies, respectively. Gram-negative bacteria such as Burkholderia pseudomallei and Klebsiella pneumoniae were also frequently diagnosed, particularly in bacteremic CAP in Thai adults and Cambodian children. In Thailand and Vietnam, Mycoplasma pneumoniae and Chlamydia pneumoniae were frequently identified in settings using indirect laboratory testing. Conclusions Based on this analysis, CAP data in Cambodia seems to present etiological and resistance profiles comparable to those of neighboring countries. Findings have been shared with the national authorities upon the revision of the national therapeutic guidelines and were disseminated using a specially created website.