Abstract

sBackgroundResistance to antimicrobial agents of pathogenic bacteria has become a major problem in routine medical practices. Carbapenem resistance has long been increasing. The production of carbapenem- hydrolysing β-lactamases (carbapenamases), which include NDM, KPC, OXA-48, IMP-1 and VIM is the most common mechanism.Case presentationA 56 years old male presented with fever and mental changes with progressively decreasing sensorium for the last 3 days. He was admitted to Intensive care unit (ICU) with a diagnosis of meningoencephalitis. On day seven, he developed ventilator associated pneumonia due Klebsiella pnemoniae and Acinetobacter baumannii. He was on meropenem, but the isolates were susceptible to colistin, tigecyclin and amikacin solely. Hence, amikacin was started with addition of intravenous and nebulized colistin. Subsequently, vital signs improved with resolution of fever. However, on day 18, he developed fever once again with a drop in blood pressure. Inotropic support was maintained, and echinocandins and tigecycline were added to the regimen.Repeat blood and urine culture grew Providencia species, which were resistant to most of the drugs on phenotypic Kirby-Bauer disk diffusion method and are intrinsically resistant to colistin and tigecycline. Phenotypic detection of ESBL (combined disk method), MBL, KPCs, AmpC and co-producer were tested according to updated CLSI guideline and all were negative. But the Modified Hodges test was found to be positive. Consequenty, OXA-48 drug resistance pattern was brought into action by blank disc method according to A Tsakris et al., which revealed indentation of growth toward both EDTA and EDTA/PBA disk indicating production of OXA-48 carbapenamase. To confirm the resistance pattern we processed the isolated colonies for Xpert Carba-R (Cepheid) assay, which detected blaOXA-48 gene and confirmed the OXA-48 drug resistance pattern. Hence, the infecting organism was not susceptible to any of the antibiotics. The patient was kept under isolation and on 31th day of admission, he died of septic shock.ConclusionsCarbapenamase production along with intrinsic colistin resistance in infecting bacterial pathogens can cause fatal outcomes in the resource limited countries like Nepal where new antibiotic combinations ceftazidime+ Avibactam, or aztreonam +avibactam are not available. Drug resistance patterns including OXA 48 producer should be characterized in all cases by standard phenotypic methods or by Xpert Carba-R assay and larger studies are required to know the exact burden of OXA 48 producer in Nepal.

Highlights

  • Resistance to antimicrobial agents of pathogenic bacteria has become a major problem in routine medical practices

  • Drug resistance patterns including OXA 48 producer should be characterized in all cases by standard phenotypic methods or by Xpert Carba-R assay and larger studies are required to know the exact burden of OXA 48 producer in Nepal

  • Antibiotic susceptibility testing was done by Kirby Bauer method according to Clinical and Laboratory Standards Institute (CLSI) (Clinical & Laboratory Standards Institute) [8] which revealed pan-drug resistant isolate

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Summary

Background

The development of antibiotics remains one of the most significant advances in modern medicine. We report an OXA-48 drug resistance pattern observed in blood and urinary isolates of Providencia species in a fatal meningoencephalitis case who subsequently developed ventilator associated pneumonia and urinary tract infection. Antibiotic susceptibility testing was done by Kirby Bauer method according to CLSI (Clinical & Laboratory Standards Institute) [8] which revealed pan-drug resistant isolate (resistance to almost all drugs available in the laboratory like amoxycillin/ampicillin, ciprofloxacin, levofloxacin, amikacin, gentamicin, meropenem, imipenem, erythromycin, clindamycin, ceftriaxone, ceftazidime, cefoperazone-sulbactam, ampicillin-sulbactum, chloramphenicol, tetracycline, doxycyclin and since Providencia species belongs to tribe Proteeae of family Enterobacteriaceae, they are intrinsically resistant to colistin and tigecycline and drug susceptibility testing is not recommended for this group of organisms). On 31th day of admission he died of septic shock and lack of other antibiotic option (intrinsic resistance to colistin and unavailability of ceftazidime+ avibactam or aztreonam +avibactam combination in both Nepal and India for testing in laboratory or for systemic use in patient)

Conclusions
Findings
Discussion and conclusion

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