Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes

Alexandrova, L. А.; Haque, Farhana; Rodríguez, Patricia Hernández; Marrazzo, Ashton C; Grembi, Jessica A.; Ramachandran, Vasavi; Hryckowian, Andrew J.; Adams, Christopher M.; Siddique, Shah Alam; Khan, Ashraful Islam; Qadri, Firdausi; Andrews, Jason R; Rahman, Mahmudur; Spormann, Alfred M.; Schoolnik, Gary K.; Chien, Allis; Nelson, Eric J.

doi:10.1093/infdis/jiz299

Cited by 14 publications

(30 citation statements)

References 36 publications

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“…Samples with C T values from 25 to 31 were evaluated for the second target of ompW by PCR and gel electrophoresis, given that this C T value range is vulnerable to false positives and negatives (8). In parallel, nl-qPCR was performed in technical replicates with tcpA set1 primers and additional targets (27,28). SYBR Green master mix (Sigma-Aldrich) was used for both qPCR and nl-qPCR; however, there was 1.8-fold more DNA in nl-qPCRs.…”

Section: Methodsmentioning

confidence: 99%

“…For samples collected in Bangladesh, the methods have been previously described ( 27 ). In brief, the first stool sample voided was collected immediately after admission to avoid exposure to hospital-administered antibiotics.…”

Section: Methodsmentioning

confidence: 99%

“…In brief, the first stool sample voided was collected immediately after admission to avoid exposure to hospital-administered antibiotics. The supernatants from V. cholerae -positive stools were tested for antibiotic exposure using a liquid chromatography-mass spectrometry (LC-MS) protocol for a 1100 series high-performance liquid chromatograph (Agilent Technologies) integrated with an LTQ XL ion trap mass spectrometer (Thermo Fisher Scientific) ( 27 ). The stool samples were tested by a dipstick RDT (Crystal VC, Span Diagnostics) after enrichment in APW for 6 h or overnight ( 36 ).…”

Section: Methodsmentioning

confidence: 99%

“…Diagnostically, culture and PCR are the best available gold standards for the detection of V. cholerae ( 24 , 25 ). Alternative methods include direct immunofluorescence microscopy for the O-antigen polysaccharide (OPS) ( 26 ), rapid diagnostic tests (RDTs) that rely on OPS-specific antibodies, and, recently, nanoliter quantitative PCR (nl-qPCR) ( 27 , 28 ); nl-qPCR uses standard quantitative PCR chemistry in nanoliter reaction volumes that are loaded robotically onto chips with 5,000 wells (TaKaRa Bio USA; formerly WaferGen, Inc.). RDTs are intended to be durable in field settings where clinical laboratories are not available but diagnostic information is vital to outbreak response ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

“…For cases treated with oral or intravenous rehydration, mortality rates decrease to less than one percent (5,6). Antibiotics are recommended for cholera patients with moderate to severe dehydration (7,8), but in practice most cholera patients are likely ordered antibiotics (27,36,44). Asymptomatic cases are detected by a rise in antibody titer but negative stool studies, typically by microbial culture (9).…”

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confidence: 99%

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Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics

et al. 2020

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A fundamental, clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR for V. cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics

et al. 2020

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Can technology help improve diarrhoea management?

Bhutta

2020

The Lancet Digital Health

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Antibiotic Use Prior to Hospital Presentation Among Individuals With Suspected Enteric Fever in Nepal, Bangladesh, and Pakistan

Vaidya

Aiemjoy

Qamar

et al. 2020

Clinical Infectious Diseases

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Background Antibiotic use prior to seeking care at a hospital may reduce the sensitivity of blood culture for enteric fever, with implications for both clinical care and surveillance. The Surveillance for Enteric Fever in Asia Project (SEAP) is a prospective study of enteric fever incidence in Nepal, Bangladesh, and Pakistan. Nested within SEAP, we evaluated the accuracy of self-reported antibiotic use and investigated the association between antibiotic use and blood culture positivity. Methods Between November 2016 and April 2019, we collected urine samples among a subset of SEAP participants to test for antibiotic use prior to the hospital visit using an antibacterial activity assay. All participants were asked about recent antibiotic use and had a blood culture performed. We used mixed-effect logit models to evaluate the effect of antimicrobial use on blood culture positivity, adjusted for markers of disease severity. Results We enrolled 2939 patients with suspected enteric fever. Antibiotics were detected in 39% (1145/2939) of urine samples. The correlation between measured and reported antibiotic use was modest (κ = 0.72). After adjusting for disease severity, patients with antibiotics in their urine were slightly more likely to be blood culture positive for enteric fever; however, the effect was not statistically significant (prevalence ratio, 1.22 [95% confidence interval, .99–1.50]). Conclusions The reliability of self-reported prior antibiotic use was modest among individuals presenting with fever to tertiary hospitals. While antibiotics are likely to reduce the sensitivity of blood culture, our findings indicate that there is still considerable value in performing blood culture for individuals reporting antibiotic use.

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Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes

Cited by 14 publications

References 36 publications

Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics

Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics

Can technology help improve diarrhoea management?

Antibiotic Use Prior to Hospital Presentation Among Individuals With Suspected Enteric Fever in Nepal, Bangladesh, and Pakistan

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