Erratum for Parry et al., Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A

Parry, Christopher M.; Thieu, Nga Tran Vu; Dolecek, Christiane; Karkey, Abhilasha; Gupta, Ruchi; Turner, Paul; Dance, David A. B.; Maude, Rapeephan R.; Vinh, Ha; Tran, Chinh; Thi, Phuong Le; Be, Bay Pham Van; Phi, La Tran Thi; Ngoc, Rang Nguyen; Ghose, Aniruddha; Dongol, Sabina; Thanh, Duy Pham; Thanh, Tuyen Ha; Moore, Catrin E.; Soeng, Sona; Gaind, Rajni; Deb, Monorama; Anh, Ho Van; Van, Sach Nguyen; Tinh, Hien Tran; Day, Nicholas P. J.; Dondorp, Arjen M.; Thwaites, Guy; Faiz, Mohamed Abul; Phetsouvanh, Rattanaphone; Newton, Paul N.; Basnyat, Buddha; Farrar, Jeremy; Baker, Stephen

doi:10.1128/aac.01014-15

Cited by 3 publications

(3 citation statements)

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“…On the other hand, there are limited studies regarding the efficacy of azithromycin for treating enteric fever, as well as any correlation of MICs with clinical improvement or failure [ 28 , 29 ]. In Nepal, there is no reported evidence of treatment failure on azithromycin treatment despite the fact that the increase in the MIC of azithromycin was reported from other countries [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Renaissance of Conventional First-Line Antibiotics inSalmonella entericaClinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric Fever Cases from Nepal

Khanal

Satyal

Bhetwal

et al. 2017

BioMed Research International

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Enteric fever caused by Salmonella enterica is a life-threatening systemic illness of gastrointestinal tract especially in tropical countries. Antimicrobial therapy is generally indicated but resistance towards commonly used antibiotics has limited their therapeutic usefulness. Therefore, we aimed to determine the antimicrobial susceptibility pattern by minimum inhibitory concentration method of common therapeutic regimens against Salmonella enterica from enteric fever clinical cases. Salmonella enterica clinical isolates recovered from the patients with suspected enteric fever whose blood samples were submitted to microbiology laboratory of Manmohan Memorial Community Hospital, Kathmandu, from March 2016 to August 2016, were studied. These isolates were subjected to antimicrobial susceptibility testing against common therapeutic antimicrobials by Kirby-Bauer disk diffusion method. The minimum inhibitory concentration of ciprofloxacin, azithromycin, chloramphenicol, and cefixime was determined by Agar dilution method based on the latest CLSI protocol. A total of 88 isolates of Salmonella enterica were recovered from blood samples of enteric fever cases. Out of them, 74 (84.09%) were Salmonella Typhi and 14 (15.91%) were Salmonella Paratyphi A. On Kirby-Bauer disk diffusion antimicrobial susceptibility testing, entire isolates were susceptible to cotrimoxazole, cefixime, ceftriaxone, azithromycin, and chloramphenicol. Sixty-four (72.7%) Salmonella enterica isolates were nalidixic acid resistant and nonsusceptible to ciprofloxacin and levofloxacin. On MIC determination, four Salmonella isolates were ciprofloxacin resistant with MIC 1 µg/ml and two isolates were ciprofloxacin intermediate with MIC 0.5 µg/ml. The MIC range of azithromycin was from 0.125 µg/ml to 2.0 µg/ml, whereas that for chloramphenicol was 2.0 µg/ml–8.0 µg/ml and for cefixime was 0.0075–0.5 µg/ml, respectively. Despite global surge of antimicrobial resistance among Salmonella enterica clinical isolates, the level of drug resistance in our study was not so high. However, higher level of NARST strains limits therapeutic use of fluoroquinolones and necessitates the routine monitoring of such resistance determinants in order to effectively and rationally manage enteric fever cases.

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Section: Discussionmentioning

confidence: 99%

Renaissance of Conventional First-Line Antibiotics inSalmonella entericaClinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric Fever Cases from Nepal

Khanal

Satyal

Bhetwal

et al. 2017

BioMed Research International

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“…Genomic surveillance also enables the identification and characterization of new resistance phenotypes, as was the case for XDR typhoid [ 8 ] and the new azithromycin-resistant organisms identified in Bangladesh and described further here [ 9 ]. The outputs of antimicrobial susceptibility testing are not always straightforward, particularly in cases where susceptibility breakpoints have not been validated extensively using clinical data, as is the case for azithromycin [ 36 ]. Genomic AMR data can inform prioritization of TCV introduction, as well as implementation of WASH interventions.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India

Carey

Jain²,

Yousuf

et al. 2021

Clinical Infectious Diseases

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Background The 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 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. Methods Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis. Results We identified 7 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 seven 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. Conclusions The 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 in the region.

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“…In 2010, the first azithromycin-resistant S. Serovars Paratyphi A strains unresponsive to azithromycin treatment isolated from Pakistan were reported (17). S. Serovars Typhi and Paratyphi A strains isolated between 1995 and 2010 originating from Vietnam, Bangladesh, Cambodia, India, Laos, Nepal, and Thailand were analyzed in 2015 to determine azithromycin susceptibility breakpoints (>16 µg/ml for S. Typhi) (18). Hooda et al (2019) first described the R717Q and R717L mutations present in S. Typhi and S. Paratyphi A clinical isolates, respectively, isolated between 2009 and 2016 from Bangladesh, with the first case dating at 2013.…”

Section: Introductionmentioning

confidence: 99%

Proximal binding pocket Arg717 substitutions in Escherichia coli AcrB cause clinically relevant divergencies in resistance profiles

Zwama¹,

Nishino

2021

Preprint

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Multidrug resistance (MDR) in bacteria can be caused by the over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily of proteins. These intrinsic or acquired pumps can export a wide range of antibiotics. Recently, amino acid substitutions within these pumps have been observed in resistant clinical strains. Among others, two of these worrying gain-of-function mutations are R717L and R717Q in the proximal binding pocket of efflux pump AcrB (AcrB-Sa) found in azithromycin-resistant Salmonella enterica spp. We investigated the ramifications of these (and other) mutations in phylogenetically closely related AcrB from Escherichia coli (AcrB-Ec). We found that AcrB-Ec harboring Arg717 substitutions were significantly more effective in exporting all tested macrolides, with an up to 8-fold increase in the minimum inhibitory concentration (MIC) values (from 16 to 128 µg/mL for azithromycin). Interestingly, gain-of-function was also seen for fluoroquinolones (2-fold higher MICs), while there was a consistent loss-of-function for the export of novobiocin and β-lactam cloxacillin (2-fold lower MICs), pointing to a protein adaptation, which simultaneously partly compromised the efflux ability of other compounds with different molecular properties. Disk diffusion susceptibility testing corroborated the findings, as the R717Q and R717L mutant strains had significantly smaller inhibition zones for macrolides and fluoroquinolones and a larger inhibition zone for novobiocin, compared to the wild type. The spread and independent emergences of these potent efflux pump mutations highlight the necessity of control of, and adjustments to, treatments with antibiotics and the need for novel antibiotics and efflux pump inhibitors.

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Erratum for Parry et al., Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A

Cited by 3 publications

References 0 publications

Renaissance of Conventional First-Line Antibiotics inSalmonella entericaClinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric Fever Cases from Nepal

Renaissance of Conventional First-Line Antibiotics inSalmonella entericaClinical Isolates: Assessment of MICs for Therapeutic Antimicrobials in Enteric Fever Cases from Nepal

Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India

Proximal binding pocket Arg717 substitutions in Escherichia coli AcrB cause clinically relevant divergencies in resistance profiles

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