Antimicrobial susceptibility testing and successful treatment of hospitalised patients with extensively drug-resistant Campylobacter jejuni infections linked to a pet store puppy outbreak

Abstract

Objectives: Most patients with Campylobacter infection do not require antibiotics; however, they are indicated in severe cases. Clinical breakpoints for many antibiotics are not yet established by the CLSI, making antibiotic selection for resistant infections challenging. During an outbreak of pet store puppy-associated XDR Campylobacter jejuni infections resistant to seven antibiotic classes, several patients required antibiotics. This study aimed to determine MICs of the outbreak strain for various antibiotics and describes the successful treatment of two patients using imipenem/cilastatin, a drug not traditionally used for Campylobacter infections.

Methods: We used whole-genome multilocus sequence typing (wgMLST) to determine the genetic relatedness of Campylobacter isolates collected from two human patients' stool samples with the outbreak strain. We performed extended antimicrobial susceptibility testing on 14 outbreak isolates and 6 control strains to determine MICs for 30 antibiotics (14 classes).

Results: Isolates from both patients were highly related to the outbreak strain by wgMLST. MICs indicated resistance of the outbreak strain to most antibiotic classes, except phenicols, glycylcyclines and carbapenems. Due to potential side effects of phenicols and safety issues precluding use of glycylcyclines such as tigecycline when alternatives agents are available, we used carbapenems to treat patients who were severely ill from the outbreak strain infections.

Conclusion: Stewardship and clinical vigilance are warranted when deciding whether and how to treat patients with suspected C. jejuni diarrhoea with antibiotics. Clinicians should maintain a high index of suspicion for XDR Campylobacter when patients fail to improve and consider the use of carbapenems in such settings.

Keywords: Campylobacter jejuni; Emerging infection; Extensively drug-resistant; XDR; Zoonosis.

Fig 1.

Clinical course of two patients showing the duration of diarrhoea and key exposures in days. PO, oral; IV, intravenous.

Fig. 2.

Squashtogram showing minimum inhibitory concentrations (MICs) for 14 antibiotic classes in two populations of Campylobacter jejuni isolates: outbreak isolates (n = 14^a) and control isolates (n = 6). * Indicates the MIC of the commercially available strain C. jejuni ATCC 33560. ^a One isolate was not tested for susceptibility to azithromycin, ciprofloxacin, clindamycin, erythromycin, florfenicol, gentamicin, nalidixic acid, telithromycin and tetracycline. NOTE: Interpretation of the squashtogram: a squashtogram is a visual aid for the interpretation of MIC values. This squashtogram shows the distribution of MICs for antimicrobial agents tested and allows an immediate comparative summary of resistance for specific categories of isolates. Results for 14 outbreak-associated isolates, 5 control isolates and the commercially available strain ATCC 33560 are shown here. The number of isolates falling into each MIC category is shown in a horizontal bar chart. For most antimicrobial agents tested, three categories (susceptible, intermediate and resistant) are used to interpret MICs. For each antibiotic, ∥(double lines) are used to mark the breakpoint for resistance interpretation and | (single line) is used to mark the breakpoint for intermediate interpretation (where applicable). MICs for tigecycline and tylosin are reported without breakpoints. Dilutions that were not tested are shaded in grey; when isolates were resistant to the highest dilution tested, results were reported in the next highest dilution (shaded grey).