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Raising the Alarm: Detection of OXA-181 Carbapenemase in Shigella Flexneri and its Implications

Recent observation has led to the detection of OXA-181 carbapenemase in azithromycin-resistant Shigella species, specifically Shigella flexneri. This discovery is occurring in an immunocompromised patient suffering with Shigellosis, a severe gastrointestinal disease typically found in economically disadvantaged and densely populated communities. These areas often suffer from poor sanitation, inadequate hygiene and unsafe water supply.

Shigella bacteria, contributing to a significant proportion of acute bloody diarrhea worldwide, primarily impacts children under five and often leads to a high mortality rate. The current development of multidrug-resistant Shigella strains is cause for growing concern. This variety of bacteria has shown resistance to multiple first-line oral antimicrobials such as ampicillin, trimethoprim/sulfamethoxazole, and ciprofloxacin. Furthermore, the existence of enzyme-mediated β-lactam resistance in Shigella renders it extensively drug-resistant, complicating issues related to empiric therapy.

Although extremely drug-resistant strains have remained susceptible to carbapenem therapy, new reports have recorded carbapenem resistance in Shigella species. We detail a case involving the impacting OXA-181–producing S. flexneri, detected from the stool of an immunocompromised patient diagnosed with B-cell acute lymphoblastic leukemia (B-ALL).

Patient’s condition worsened still under the carbapenemase-producing Enterobacterales (CPE) screening, during which the stool sample showed growth of non–lactose fermenting colonies confirmed as S. flexneri bacteria type 2a. Despite susceptibility to meropenem, it’s important to note MIC values above the 0.12 mg/L CPE screening cut-off, which further led to an OXA-48–like enzyme, as indicated by a CARBA-5 assay. The test results altered the patient’s treatment from azithromycin to trimethoprim/sulfamethoxazole, since azithromycin resistance was noticed.

The disturbing revelation of an OXA-181 carbapenemase in a plasmid carried by S. flexneri positions a colossal challenge on global healthcare, particularly threatening for densely populated low to middle-income communities. This discovery reinforces the necessity for a consistent and targeted surveillance for CPE in high-risk patients.


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