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Extreme Drug Resistance of catheter-associated Escherichia coli Urinary Tract Infections in Long-Term Care Setting: A Case Report

Kay Thwe Kyaw, DrPH, M.B.,B.S,MPH

Objective:

To raise awareness of the occurrence of extreme drug resistance (XDR) in Escherichia coli (UPEC) strains ESBLs in urinary catheter-associated urinary tract infections in long-term care settings.

Background:

The urinary tract infections (UTIs) are the most common site of infections around the world, including the residents of long-term care facilities (LTCFs). UTIs are the most common reason for prescribing antibiotics in LTCFs. Among risk factors for UTIs, indwelling urinary catheters cause both symptomatic UTIs and asymptomatic UTIs.

Indwelling urinary catheters are necessary for specific medical conditions, such as individuals having neurogenic bladder, chronic obstruction of the urinary outflow tract, and a particular type of urological cancer. Symptomatic bacteriuria UTIs present with fever, cloudy urine, altered mental status, hypotension, tenderness at the suprapubic area, and culture growth of ≥ 103 (cfu/ml) of uropathogenic bacteria, while asymptomatic bacteriuria presents with culture growth of ≥ 105 (cfu/ml) of uropathogenic bacteria in the absence of signs and symptoms of UTIs. There is some evidence showing that the incidence of catheter-associated UTIs in 2012 was 1.4 to 1.7 per 1, 000 catheter days in adult and pediatric hospitalized patients. (Centers for Disease Control and Prevention). Moreover, the residents in LTCFs serve as reservoirs for those organisms, and the colonization rates with those strains are comparable with colonization rates in acute care hospitals. Interestingly, bacterial colonization of the drainage bag is one of the risk factors for catheter-associated UTIs.

As far as pathogenesis is concerned, extraluminal infection occurs through the incidental introduction of biofilm of bacteria surrounding the urethra into the bladder, and intraluminal infection occurs from urinary stasis in the bladder from failure to drain urine properly. This case report mentions the recurrent nature of uropathogenic bacteria: Escherichia coli (E. coli), along with treatments, and developed resistance to fluoroquinolones and subsequently developed extreme drug resistance.

Report of a Case:

A 63-year-old male, long-term care resident, with a chronic indwelling urinary catheter for neurogenic bladder from paraplegia, has had multiple episodes of UTIs since March 2018. During 2017, he had 3 episodes of pneumonia and was treated with Levofloxacin 750 mg PO once daily for 5 days for pneumonia and required treatment with Cephalexin 500 mg PO twice daily for 7 days for lower extremities cellulitis, where culture was not done. In January 2018, patient was again treated with Levofloxacin 750 mg PO once daily for 5 days for pneumonia. Two months later, patient developed urine culture-positive E. coli UTIs, which were resistant to Ciprofloxacin/Levofloxacin/ Nitrofurantoin/Tetracycline, and was treated with Augmentin as per urine culture sensitivity results. Later in June 2018, he was again found to have a urine culture positive E. coli UTIs, which were similar to previous episodes and showed resistance to Ciprofloxacin/Levofloxacin/ Nitrofurantoin/Tetracycline, and again was treated with Augmentin.

Other episodes of positive E. coli UTIs that were resistant to Ciprofloxacin/Levofloxacin/Tetracycline/Cefepime/Cefotaxime /Claforan/Ceftazidime and treated with Nitrofurantoin as per sensitivity results. He was required to be admitted to the hospitalfor Acute Kidney Injury in October 2018 and found to have extremely drug-resistant E. coli UTIs, which were sensitive to IV Meropenem. No more episodes of signs and symptoms of UTIs after treating with IV Meropenem.

Table 1.1 shows episodes of E. coli UTIs, urine culture, and sensitivity

Date	Urine Culture (>100,000 colonies OB)	Resistance	Sensitive	Treatment
03/25/2018	E.Coli/Proteous Mirabilis	Ciprofloxacin/Levofloxacin/Nitrofurantoin/Tetracycline	Augmentin/Amp/Sulbactam/Ertapenem/Pip/Tazobactam/Cefepine/Cefotaxime/Claforan/Ceftazidime	Augmentin
06/14/2018	E. coli	Ciprofloxacin/Levofloxacin/Nitrofurantoin/Tetracycline/Cefepine/Cefotaxime/Claforan/ceftaziime	Augmentin/Ertapenem/Pip/tazobactam	Augmentin
08/10/2018	E. coli	Ciprofloxacin/Levofloxacin/Tetracycline/Cefepine/Cefotaxime/Claforan/ceftaziime	Augmentin/Ertapenem/Pip/tazobactam/Nitrofurantoin	Nitrofurantoin
10/22/2018	E. coli	Extreme drug resistance	Meropenem	Meropenem

Discussion:

According to global surveillance data, there is a rising trend of antibiotic resistance, which has become a significant public health problem. In addition, E. coli UTIs are one of the global public health concerns due to their high multidrug resistance and virulence factors. The modern evolutions of antibiotic resistance, which are believed to originate from the ancient origin and the genetic variations, lead to the emergence and spread of many drug resistances with complex genotype and phenotype against antibiotic resistance through the natural selection process in microorganisms. Fluoroquinolone resistance and extended-spectrum beta-lactamases (ESBLs) producing, Enterobacteriaceae, including E. coli, have been increasing globally. The infections caused by multidrug-resistant and extreme drug-resistant E. coli, along with other Enterobacteriaceae, are associated with high public health costs, therapeutic failures, restriction of the antibacterial agent’s choice, increased duration of hospitalization, high morbidity, and mortality.

The mechanism of quinolone resistance is chromosomal mutations in the quinolone resistance- determining region of genes encoding DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes, plasmid-mediated quinolone resistance (PMQR) determinants, and plasmid- mediated efflux pumps. Due to the discoveries of my research, there is a better understanding of the molecular mechanism behind fluoroquinolone resistance and extended-spectrum β-lactamases in terms of the structural and functional aspects of drug transporters across the cells, along with their regulations and inhibitions. Multidrug efflux pumps such as RND superfamily pumps, MATE, SME, ABC, and MFS actively pump out drugs.

Multidrug efflux pumps are usually coded by chromosomal genes and can be overexpressed easily, and can pump out most of the current antibiotics. In addition, multidrug resistance in bacteria is often caused by the accumulation of genes coding for resistance to a single drug on R plasmids by transposons, integrons, and ISCR elements. Among them, integrons are powerful in producing multidrug resistance because they assemble several resistance genes in a correct orientation and supply a strong promoter for their expression. Most importantly, the persistence of pathogenic microorganisms in an antibiotic-treated individual could get into a physiologically resistant state without any genetic changes. In the above patient, it could be explained that previous introduction of fluoroquinolones for the treatment of pneumonia, along with UTIs and treatment of cellulitis with cephalosporines, led to the development of an extremely drug-resistant E. coli UTI.

Conclusion:

It is vital to prevent episodes of UTIs in individuals with an indwelling urinary catheter to prevent multidrug resistance and extreme drug resistance E. coli UTIs. Important steps for prevention of catheter-associated UTI include avoidance of unnecessary catheterization, use of sterile technique for catheter placement, and removal of the catheter as soon as possible. Moreover, education of the provider about the guidelines for prescribing antibiotics for UTIs which include prescribing antibiotics for symptomatic UTIs, establishing antibiotic surveillance in the LTCFs, and health education to the patients and families regarding emerging antibiotics resistance.

It is concluded that more research and surveillance of catheter-associated UTIs to develop policy in LTCFs to prevent multidrug resistance and extreme drug resistance in E. coli Catheter-associated UTIs in LTCFs to prevent high mortality and morbidity.

Reference:

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For more information of antibotic resistence information could be found at CDC ‘s antimicrobial-resistance