scholarly journals Spontaneous emergence of azithromycin resistance in independent lineages of Salmonella Typhi in Northern India

2020 ◽  
Author(s):  
Megan E. Carey ◽  
Ruby Jain ◽  
Mohammad Yousuf ◽  
Mailis Maes ◽  
Zoe A. Dyson ◽  
...  

AbstractBackgroundThe emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug resistant (XDR) Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal.MethodsHere, we aimed to understand the molecular basis of AMR in 66 S. Typhi isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole genome sequencing (WGS) and phylogenetic analysis.ResultsWe identified seven S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal.ConclusionsThe independent emergence of azithromycin resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines (TCVs) in the region.Key pointsWe identified ciprofloxacin/azithromycin-resistant Salmonella Typhi (S. Typhi) in Chandigarh in Northern India. The independent emergence of ciprofloxacin/azithromycin-resistant typhoid in Bangladesh, Pakistan, Nepal, and India and the continued spread of extensively-drug resistant (XDR) typhoid in Pakistan highlight the limitations of licensed oral treatments for typhoid fever in South Asia.

2020 ◽  
Vol 24 (4) ◽  
pp. 406-411
Author(s):  
Kausar Izhar ◽  
Kiran Ahmed ◽  
Maryyam Rehan ◽  
Muhammad Umar ◽  
Nadeem Ikram ◽  
...  

Objective: To evaluate the prevalence of extensively drug-resistant Salmonella typhi (XDR) in RMU Allied Hospitals. Study Design: A descriptive cross-sectional study. Material and Methods: It is a cross-sectional, prospective study conducted at RMU Allied Hospitals from January 2019–December 2019. Blood culture samples were received in the pathology lab, they were collected by simple random sampling and processed by conventional incubation. Antibiotic susceptibility of the isolates was done on Muller Hinton agar using modified Kirby Bauer disk diffusion method and antibiotic zone diameters were measured according to CLSI guidelines. Results: Out of the total 8045 cultures, 911 (11%) showed growth, among which 179 (20%) were Salmonella typhi and 135 (15%) XDR Salmonella. Meropenem revealed the highest sensitivity, Chloramphenicol, and Augmentin revealed the highest resistance. Conclusion: Blood culture results revealed Salmonella typhi 20% with a significant number of XDR Salmonella 15%. Antibiotics susceptibility pattern exhibits Meropenem and Azithromycin as the only antibiotics for XDR Salmonella. Salmonella typhi infection has a significantly high prevalence among children as compared to adults. (p=0.0017) Injudicious use of antibiotics is one of the important aspects of the occurrence of antibiotic-resistant Salmonella.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S99-S100
Author(s):  
Felicita Medalla ◽  
Louise Francois Watkins ◽  
Michael Hughes ◽  
Meseret Birhane ◽  
Layne Dorough ◽  
...  

Abstract Background Typhoid fever, caused by Salmonella Typhi, is fatal in 12%–30% of patients not treated with appropriate antibiotics. In 2016, a large outbreak of extensively drug-resistant (XDR) Typhi infections began in Pakistan with cases reported globally, including the United States. In 2021, the Centers for Disease Control and Prevention (CDC) issued a health advisory on XDR infections among U.S. residents without international travel. We describe resistance of Typhi infections diagnosed in the United States to help guide treatment decisions. Methods Typhoid fever is a nationally notifiable disease. Health departments report cases to CDC through the National Typhoid and Paratyphoid Fever Surveillance system. Isolates are submitted to the National Antimicrobial Resistance Monitoring System for antimicrobial susceptibility testing (AST) using broth microdilution. AST results are categorized by Clinical and Laboratory Standards Institute criteria. We defined XDR as resistant to ceftriaxone, ampicillin, chloramphenicol, and co-trimoxazole, and nonsusceptible to ciprofloxacin. Results During 2008–2019, of 4,637 Typhi isolates, 52 (1%) were ceftriaxone resistant (axo-R); 71% were ciprofloxacin nonsusceptible, 1 azithromycin resistant (azm-R), and none meropenem resistant. XDR was first detected in 2018, in 2% of 474 isolates and increased to 7% of 535 in 2019. Of the 52 axo-R isolates, 46 were XDR, of which 45 were from travelers to Pakistan, and one from a non-traveler; 6 were not XDR, of which 4 were linked to travel to Iraq. In preliminary 2020 reports, 23 isolates were XDR; 14 were from travelers to Pakistan, 8 from non-travelers, and 1 from someone with unknown travel status. Among those with XDR infection, median age was 11 years (range 1–62), 54% were female, and 62% were from 6 states. Conclusion Ceftriaxone-resistant Typhi infections, mostly XDR, are increasing. Clinicians should ask patients with suspected Typhi infections about travel and adjust treatment based on susceptibility results. Carbapenem, azithromycin, or both may be considered for empiric therapy of typhoid fever among travelers to Pakistan or Iraq and in uncommon instances when persons report no international travel. Ceftriaxone is an empiric therapy option for travelers to countries other than Pakistan and Iraq. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 71 (5) ◽  
pp. 1615-18
Author(s):  
Sunila Tashfeen ◽  
Naveed Asif ◽  
Muhammad Farooq

Objective: To assess and compare the frequency of haematological parameter derangements in patients due to non-resistant and extended drug resistant (XDR) typhoid fever. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department of Combined Military Hospital Quetta, from Jan to Dec 2019. Methodology: A total number of 172 blood culture Salmonella positive patients irrespective of age and gender were included in this study. Salmonella strains were isolated and grouped further according to their drugs sensitivity. 3ml venous blood was collected from these patients in Ethylene diamine tetra acetic acid container and blood complete count was done by semiautomated haematology analyser XP-100. Results: There were 126 (73%) males and 46 (27%) females with mean age of 17.5 ± 10.3 years. Out of 172 subjects, 106 (61.6%) had non-resistant typhoid and rest 66 (38.4%) were diagnosed with extended drug resistant Typhoid. We compared anaemia, leucopenia and thrombocytopenia between two groups and found anaemia statistically significant with the p-value of 0.001. Conclusion: This study has documented that changes in haematological parameters are significant in typhoid fever and early patients diagnosis, management and disease course can be monitored with them. Patients with significant anaemia and not responding to first line therapy should be considered as a case of extended drug resistant (XDR) Salmonella.


Author(s):  
Aravind Gandhi P ◽  
Tanveer Rehman ◽  
Divya Ilanchoorian ◽  
Soundappan Kathirvel

Abstract Objectives The study assessed the community preparedness to manage the COVID-19 and access to healthcare services during the lockdown of 2020 in a rural health block of northern India. Methods A cross-sectional study was conducted during June-July, 2020 in 25 villages and five wards of a rural administrative block of Haryana. A pre-tested, semi-structured investigator administered checklist was used to assess the community preparedness and practices for COVID-19 prevention/control and healthcare access through direct observations and interviewing community health workers and beneficiaries. Results Active surveillance for influenza-like illness was carried out in 86.7% of the study units, though the frequency was once a month. There was poor adherence (adherence: 0-3%) to COVID-19 infection prevention & control (IPC) measures such as physical distancing and use of face masks. Rural beneficiaries reported difficulty accessing essential healthcare services than their urban counterparts. Conclusion A qualitative study to understand the facilitators and barriers for the non-adherence to IPCs measures by the study population and formulating behaviour change communication strategies for improving the IPCs is needed. Repeat, cross-sectional surveys at regular intervals may be planned to gauge the change and effect of the interventions on the community preparedness and practices.


Author(s):  
Sadia Hameed

Introduction: Typhoid fever is a public health issue, burdening many regions of the world with poor socioeconomic background. Management of this disease faces the major hurdle of antimicrobial resistance. The present study reveals current pattern of antimicrobial susceptibility among Salmonella enterica (Salmonella typhi & Salmonella paratyphi A) blood culture isolates from typhoid fever cases. Regular data collection about Salmonella infections and their response to antimicrobial agents, coupled with a long term commitment to providing adequate health information systems, is the key to effective planning and policy formation against typhoid fever. Aims & Objectives: To evaluate the prevalence of ceftriaxone resistant Salmonella enterica isolates from blood cultures in Shaikh Zayed Medical Complex for updating nosocomial antimicrobial resistance data. Place and duration of study: This research study was conducted at Shaikh Zayed Medical Complex, Lahore from March 2018 to May 2019. Material & Methods: Blood cultures positive for Salmonella enterica were analyzed, taking into consideration the gender & age of patients with typhoid fever. Antimicrobial susceptibility testing was carried out through disc diffusion method. The recommended antimicrobial agents for S. typhi (Salmonella typhi) & S. paratyphi A (Salmonella Parathyphi A) (as per CLSI, USA 2018/2019 guidelines; described later), were tested and analyzed during this study with the main focus on 3rd generation cephalosporin resistance pattern. Among second line treatment options, meropenem and azithromycin were selected for study. Results: Out of 899 isolates of Salmonella enterica (from 13964 samples for blood culture), 849 (94.4%) were S. typhi and 50 (5.6%) were S. paratyphi A. Of these, 57.1% isolates were from males, 42.9% from females, 81.7% from children (age less than 12 years) and 18.3% were from adults (age more than 12 years). A continuously rising resistance percentage was observed for 3rd generation cephalosporins over the span of fifteen months. It was 43.4% for ceftriaxone (CRO). No case of meropenem and azithromycin resistance was observed during study period. Conclusion: Demographic information was provided by this study regarding high level of resistance among Salmonella enterica isolates particularly S. typhi .The first line antibiotic drugs were a complete failure in ongoing outbreak of typhoid fever. The novel results of this study are the high resistance percentages for 3rd generation cehalosporins, whether oral or parenteral. This result is worrisome as it will leave us with no option but to resort to second line drugs. However, an increasing trend of blood culturing was observed in this research. Extensively drug resistant (XDR) Salmonella infection has definitely highlighted the importance of blood culture and its use as a more preferred diagnostic tool. Key words: Typhoid fever, Extensively drug resistant (XDR) Salmonella enterica, (S. typhi & S. paratyphi A), Antimicrobial Resistance, CRO (Ceftriaxone) resistance.


2021 ◽  
Author(s):  
Chanmi Kim ◽  
Iqra Latif ◽  
Durga P Neupane ◽  
Gi Young Lee ◽  
Ryan S Kwon ◽  
...  

Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients to determine their antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and control strategies for XDR S. Typhi.


2021 ◽  
Author(s):  
Parinitha Kaza ◽  
Basil Britto Xavier ◽  
Jaspreet Mahindroo ◽  
Stephen Baker ◽  
To Nguyen Thi Nguyen ◽  
...  

Klebsiella pneumoniae associated with hospital acquired infections in South Asia are frequently extensively-drug resistant, making treatment and control problematic. It is important to understand the epidemiology and genetic structure of XDR K. pneumoniae and to determine their potential to be hypervirulent (hv) through the presence of siderophores. Here, we characterized the genomes of 20 colistin-resistant XDR K. pneumoniae isolated from 16 patients with complicated UTI over a six-month period in a healthcare facility in northern India. The 16 organisms comprised five STs: ST14 (10/20), ST147 (5/20), ST231 (3/20), ST2096 (1/20), and ST25 (1/20). Notably, several patients admitted to a single ward were infected with the same ST, potentially indicating a common infection source. Additionally, some patients had recurrent infections with multiple STs that were circulating concurrently in a particular ward, providing further evidence for hospital transmission. Beta lactamase genes (blaCTX-M-1, blaSHV, blaLEN, and blaAMP-H) were present in all isolates and the blaNDM, blaOXA1-90, and blaOXA48 carbapenemases were present in 17, 18, and 3 isolates, respectively. Disruption of mgrB with various IS elements was identified in six organisms and was the most common mechanism of colistin resistance. The most frequent K type was K2 (11/20), followed by K10, K51, and K64. Notably, we identified one XDR convergent hypervirulent K. pneumoniae (hvKp) associated with prolonged hospitalisation (iuc+ybt+ESBL+OXA-1, OXA-48), belonging to ST2096. Our data suggest that convergent XDR-hvKp is circulating in our healthcare facility. We speculate that such organisms may have outbreak potential, warranting more effective antimicrobial stewardship and better infection control strategies.


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