Emergence of #ceftriaxone #resistance during a #pneumococcal #meningitis with #fatal evolution (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Emergence of ceftriaxone resistance during a pneumococcal meningitis with fatal evolution

A. Mizrahi, J.C. Marvaud, B. Pilmis, J.C. Nguyen Van, C. Couzigou, C. Bruel, N. Engrand, A. Le Monnier, T. Lambert

DOI: 10.1128/AAC.01958-19



We report a case of a 62-year old man treated for a Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After a neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in serum and CSF. S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid ten days after the isolation of the first strain. Isolates analysis showed that a mutation of penicillin-binding proteins in PBP2x has occurred under treatment.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Ceftriaxone; Streptococcus pneumoniae; Meningitis.


Molecular #Epidemiology of #Ceftriaxone Non-Susceptible #Enterobacterales Isolates in an Academic #Medical Center in the #USA (Open Forum Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Open Forum Infect Dis. 2019 Aug 11. pii: ofz353. doi: 10.1093/ofid/ofz353. [Epub ahead of print]

Molecular Epidemiology of Ceftriaxone Non-Susceptible Enterobacterales Isolates in an Academic Medical Center in the United States.

Tamma PD1, Shahara SL1, Pana ZD2, Amoah J3, Fisher SL4, Tekle T4, Doi Y5, Simner PJ1.

Author information: 1 Johns Hopkins University School of Medicine Baltimore, MD, USA. 2 European University of Cyprus Nicosia, Cyprus. 3 Johns Hopkins University School of Medicine Baltimore, Maryland, USA. 4 Johns Hopkins Hospital Baltimore, Maryland, USA. 5 University of Pittsburgh Pittsburgh, Pennsylvania, USA.




Knowledge of whether Enterobacterales are not susceptible to ceftriaxone without understanding the underlying resistance mechanisms may not be sufficient to direct appropriate treatment decisions. As an example, extended-spectrum β-lactamase (ESBL)-producing organisms almost uniformly display non-susceptibility to ceftriaxone. Regardless of susceptibility to piperacillin-tazobactam or cefepime, carbapenem antibiotics are the treatment of choice for invasive infections. No such guidance exists for ceftriaxone non-susceptible organisms with mechanisms other than ESBL production. We sought to investigate the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales.


All consecutive Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis clinical isolates with ceftriaxone MICs of ≥2 mcg/mL from unique patients at a United States hospital over an 8-month period were evaluated for β-lactamase genes using a DNA microarray-based assay.


Of 1929 isolates, 482 (25%) had ceftriaxone MICs of ≥2 mcg/mL and were not resistant to any carbapenem antibiotics. Of the 482 isolates, ESBL (blaCTX-M, blaSHV, blaTEM) and/or plasmid-mediated ampC (p-ampC) genes were identified in 376 (78%). ESBL genes were identified in 310 (82.4%), p-ampC genes in 2 (0.5%), and both ESBL and p-ampC genes in 64 (17.0%) of the 376 organisms. There were 211 (56%), 120 (32%), 41 (11%), and 4 (1%) isolates with 1, 2, 3, or 4 or more ESBL or p-ampC genes. The most common ESBL genes were of the blaCTX-M-1 group (includes blaCTX-M-15) and the most common p-ampC gene was the blaCMY-2.


There is considerable diversity in the molecular epidemiology of ceftriaxone non-susceptible Enterobacterales. An understanding of this diversity can improve antibiotic decision-making.

© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

KEYWORDS: Enterobacteriaceae ; Check-Points; ESBL; ampC beta-lactamase; antimicrobial resistance; extended-spectrum beta-lactamase

PMID: 31401649 DOI: 10.1093/ofid/ofz353

Keywords: Antibiotics; Drugs Resistance; Enterobacteriaceae; Ceftriaxone; USA.


#Antibiotics with activity against #intestinal #anaerobes and the #hazard of acquired #colonization with #ceftriaxone-resistant Gram-negative pathogens in #ICU patients: a propensity score-based analysis (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Antibiotics with activity against intestinal anaerobes and the hazard of acquired colonization with ceftriaxone-resistant Gram-negative pathogens in ICU patients: a propensity score-based analysis

Maxime Boutrot, Khalid Azougagh, Jérôme Guinard, Thierry Boulain, François Barbier

Journal of Antimicrobial Chemotherapy, dkz279, https://doi.org/10.1093/jac/dkz279

Published: 09 July 2019




Intestinal colonization resistance is mainly exerted by commensal anaerobes.


To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients.

Patients and methods

All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition.


Among the 352 included patients [median ICU stay 16 (9–30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12–13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46–12.63, P = 0.01). Exposure to other antimicrobials—especially ceftriaxone and imipenem/meropenem—exerted no independent impact on the likelihood of CFR-GNB acquisition.


Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity.

Topic: antibiotics – ceftriaxone – exertion – carbapenem – amoxicillin-potassium clavulanate combination – anaerobic bacteria – disease transmission – imipenem – intensive care unit – intestines – metronidazole – aryl hydrocarbon receptor – meropenem – piperacillin/tazobactam – pathogenic organism – antimicrobials – microbial colonization


© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Ceftriaxone; Enterobacteriaceae; ICU.


Post-exposure administration of a #Yersinia pestis live #vaccine potentiates second-line #antibiotic #treatment against #pneumonic #plague (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Post-exposure administration of a Yersinia pestislive vaccine potentiates second-line antibiotic treatment against pneumonic plague

A Zauberman, D Gur, Y Levy, M Aftalion, Y Vagima, A Tidhar, T Chitlaru, E Mamroud

The Journal of Infectious Diseases, jiz260, https://doi.org/10.1093/infdis/jiz260

Published: 16 May 2019



Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing contagious disease. In the plague mouse model, a single immunization with the EV76 live attenuated Y. pestis strain rapidly induced the expression of hemopexin and haptoglobin in the lung and serum, both of which are important in iron sequestration. Immunization against a concomitant lethal Y. pestis respiratory challenge was correlated with temporary inhibition of disease progression. Combining EV76-immunization and second-line antibiotic treatment, which are individually insufficient, led to a synergistic protective effect that represents a proof of concept for efficient combinational therapy in cases of infection with antibiotic-resistant strains.

Y. pestis, plague, antibiotic therapy, EV76, vaccine, ceftriaxone, infection

Issue Section: Brief Report

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Yersinia pestis; Vaccines.


#Gentamicin compared with #ceftriaxone for the #treatment of #gonorrhoea (G-ToG): a randomised non-inferiority trial (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial

Prof Jonathan D C Ross, MD, Clare Brittain, BMedSc, Michelle Cole, DBMS, Claire Dewsnap, MD, Jan Harding, PhD, Trish Hepburn, BSc, Louise Jackson, PhD, Matthew Keogh, Tessa Lawrence, PhD, Prof Alan A Montgomery, PhD, Prof Tracy E Roberts, PhD, Kirsty Sprange, MSc, Wei Tan, MSc, Sukhwinder Thandi, PhD, John White, FRCP, Janet Wilson, FRCP, Prof Lelia Duley, MD, on behalf of theG-ToG trial team

Published: May 02, 2019 / DOI: https://doi.org/10.1016/S0140-6736(18)32817-4




Gonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea.


G-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227.


Of 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group).


Gentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea.


UK National Institute for Health Research.

Keywords: Antibiotics; Drugs Resistance; Neisseria gonorrhoeae; Ceftriaxone; Azithromycin; Gentamicin.


#Clonal expansion and spread of the #ceftriaxone-resistant #Neisseria gonorrhoeae strain FC428, identified in #Japan in 2015, and closely related isolates (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

Clonal expansion and spread of the ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, identified in Japan in 2015, and closely related isolates

Kenichi Lee, Shu-Ichi Nakayama, Kayo Osawa, Hiroyuki Yoshida, Soichi Arakawa, Kei-Ichi Furubayashi, Hiroshi Kameoka, Ken Shimuta, Takuya Kawahata, Magnus Unemo, Makoto Ohnishi

Journal of Antimicrobial Chemotherapy, dkz129, https://doi.org/10.1093/jac/dkz129

Published: 19 April 2019




Ceftriaxone resistance in Neisseria gonorrhoeae is a major public health concern globally because a high-dose (1 g) injection of ceftriaxone is the only remaining option for empirical monotherapy of gonorrhoea. The ceftriaxone-resistant gonococcal strain FC428, cultured in Osaka in 2015, is suspected to have spread nationally and internationally. We describe the complete finished genomes of FC428 and two closely related isolates from Osaka in 2015, and examine the genomic epidemiology of these isolates plus three ceftriaxone-resistant gonococcal isolates from Osaka and Hyogo in 2016–17 and four ceftriaxone-resistant gonococcal isolates cultured in 2017 in Australia, Canada and Denmark.


During 2015–17, we identified six ceftriaxone-resistant gonococcal isolates through our surveillance systems in Kyoto, Osaka and Hyogo. Antimicrobial susceptibility testing (six antimicrobials) was performed using Etest. Complete whole-genome sequences of the first three isolates (FC428, FC460 and FC498) from 2015 were obtained using PacBio RS II and Illumina MiSeq sequencing. The three complete genome sequences and draft genome sequences of the three additional Japanese (sequenced with Illumina MiSeq) and four international ceftriaxone-resistant isolates were compared.


Detailed genomic analysis suggested that the Japanese isolates (FC428, FC460, FC498, KU16054, KM383 and KU17039) and the four international MLST ST1903 isolates from Australia, Canada and Denmark formed four linked subclades.


Using detailed genomic analysis, we describe the clonal expansion of the ceftriaxone-resistant N. gonorrhoeae strain FC428, initially identified in 2015 in Japan, and closely related isolates. FC428 and its close relatives show some genomic diversity, suggesting multiple genetic subclades are already spreading internationally.


© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Antibiotics; Drugs Resistance; Ceftriaxone; Neisseria gonorrhoeae; Japan.


Sub lethal levels of #platinum #nanoparticle cures #plasmid and in combination with #carbapenem, curtails carbapenem resistant #Escherichia coli (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 28 March 2019

Sub lethal levels of platinum nanoparticle cures plasmid and in combination with carbapenem, curtails carbapenem resistant Escherichia coli

Subhashree Bharathan, Niranjana Sri Sundaramoorthy, Harini Chandrasekaran, Gagana Rangappa, GaneshPrasad ArunKumar, Siva Bala Subramaniyan, Anbazhagan Veerappan & Saisubramanian Nagarajan

Scientific Reports, volume 9, Article number: 5305 (2019)



Drug resistance traits are rapidly disseminated across bacteria by horizontal gene transfer, especially through plasmids. Plasmid curing agents that are active both in vitro and in vivo will resensitize Multi Drug Resistant (MDR) bacteria to antimicrobial agents. Pectin capped platinum nanoparticles (PtNPs) at sub MIC (20 µM) concentration was effective, in causing loss of Extended Spectrum Beta Lactamase (ESBL) harboring plasmid as evidenced by, absence of plasmid in agarose gel and by a concomitant (16–64 fold) drop in MIC for cell wall inhibitors ceftriaxone and meropenem, in carbapenem resistant Escherichia coli(CREC). Interestingly, the plasmid cured strain exhibited small colony morphology and displayed slower growth both in vitro and in vivo. Complementation of cured strain with plasmid from the wild type strain restored resistance towards meropenem and ceftriaxone. Relative to wild type, plasmid cured strain displayed 50% reduction in biofilm formation. Plasmid curing also occurred in vivo in infected zebrafish with curing efficiency of 17% for nanoparticle + meropenem treatment. PtNPs + meropenem reduced bioburden of CREC in infected zebrafish by 2.4 log CFU. Mechanistic studies revealed that nanoparticle interacted with cell surface and perturbed inner membrane integrity. PtNPs did not induce ROS, yet it caused plasmid DNA cleavage, as evidenced by gyrase inhibition assay. Our study for the first time reveals that PtNPs as plasmid curing agent can resensitize MDR bacteria to selective antimicrobial agents in vivo.

Keywords: Antibiotics; Drugs Resistance; Carbapenem; Ceftriaxone; Meropenem; E. Coli.