An outbreak of multi-drug resistant Escherichia coli urinary tract infection in an elderly population: a case-control study of risk factors

Urinary tract infections (UTIs) are the most common bacterial infection in older populations [1]. Globally there are an estimated 150 million UTIs each year leading to more than 6 billion dollars in direct healthcare costs [2]. Although for most healthy adults UTIs are an inconvenience requiring short-term antimicrobial therapy, in patients with pyelonephritis including the elderly this can lead to bacteremia, hospitalisation, systemic antimicrobial therapy, decreased functional status and death [3].

Multi-drug resistant organisms (MDRO) add further complications which result in decreased effectiveness of standard treatments [4]. The control of UTIs due to MDROs can be challenging in particular due to the frequent emergence of resistance to new antimicrobials and the spread of resistant bacteria beyond hospitals into the community including nursing homes [5]. These facilities can act as reservoirs of these MDROs which can then be transmitted to acute hospitals [5, 6]. In vulnerable populations, including nursing home residents where inappropriate treatment of asymptomatic bacteriurua may be a particular issue [7], UTIs can have higher prevalence of resistance to antimicrobials including ciprofloxacin, cephazolin, and nitrofurantoin [8]. Mortality is higher following bacteremia with strains resistant to antimicrobials than with strains sensitive to antimicrobials [9], although this is most likely due to inappropriate empiric antimicrobial therapy rather than an association with increased virulence of the E coli strains [10, 11].

Risk factors for diagnosis of UTIs caused by MDROs can be classified as individual factors, predisposing factors, and bacterial factors [3]. Individual or demographic characteristics that may affect risk of colonization of the urinary tract with MDROs include older age [8, 12‐14], female sex [8], a history of UTIs [13, 15], and diagnoses of dementia or poor functional level [5, 14], diabetes [12, 13], and prostatic disease. Predisposing or healthcare-associated factors associated with increased risk of community acquired MDROs in the urinary tract include invasive procedures such as urinary catheterisation [13, 16], previous hospitalisation [12, 13, 15], residence in a nursing home [8], and prior exposure to antimicrobials [5, 12‐19].

From 30 March 2009 to 30 June 2011 a phenotypically distinct MDR Escherichia coli (E.coli), which failed to ferment lactose on MacConkey agar and was resistant to gentamicin, quinolones including fluoroquinolones, trimethoprim, trimethoprim-sulfamethoxazole, and amoxicillin, and in this case susceptible only to nitrofurantoin and cephalosporins, was identified as the cause of 77 UTIs in South Canterbury. This is a semi-rural region in New Zealand, population 58,000. The first diagnosis of this organism was in 2007, but in 2009 the prevalence of fluoroquinolone resistance increased from 5 % E.coli isolates in 2007 to a peak of 13 % resistance in 2009 and 2010 decreasing, after interventions to 9 % in 2011. In 2009 this necessitated a change in the antimicrobial formulary to cover this MDR E. coli both for bacteraemia, with the urinary tract as the potential source, and also treatment for cystitis . Infection prevention and control strategies were introduced with a view to decreasing the transmission of this organism. These were; placing alerts on the medical records and implementing infection prevention and control precautions for cases with MDR E.coli with this phenotype in both the acute hospital and nursing homes, educating general practitioners with a view to reducing fluoroquinolone use and education sessions on infection prevention and control procedures for the staff of the local nursing homes.

Figure 1 shows the epidemic curve for the outbreak. The 5 MLST typed isolates were all E.coli ST 131. We initially identified 78 cases and 156 controls, but on review of hospital notes found that two of the cases were younger than 65 years and therefore ineligible to be cases in this study. Therefore the analysis includes data from 76 cases and 156 controls.

The characteristics of the cases and controls are shown in Table 1. Compared with controls, cases were more likely to be female, be older, live in a residential facility, have been admitted to a hospital in the past 12 months, be diabetic, have been catheterized in the past 12 months, and to have had more UTIs in the past 12 months.

Table 2 shows antimicrobial prescriptions from all settings, GP practices, and in hospital for both cases and controls. Compared with controls, cases were overall more likely to have had prescriptions of any antimicrobials and of antimicrobials to which the MDR E coli was resistant. This pattern was driven by prescribing in hospitals, and in contrast, in the GP setting about the same proportion of cases and controls had been prescribed any antimicrobials and antimicrobials to which the MDR E coli was resistant.

The main logistic regression model included the risk factors hospitalization, hospital prescription of ‘resistant’ antimicrobials, age, gender, diabetes, level of care, and recurrent UTI. A second logistic regression was performed that maximized the number of participants included by excluding diabetes and recurrent UTI, which both had more than 7 % missing values. Neither model included GP antimicrobial prescriptions, as they were not different between cases and controls, or a history of catheterisation, because 14 % of participants had missing data on this variable.

The results of the logistic regression modelling are shown in Tables 3 and 4. The highest odds ratios were for prescription in hospital of antibiotics to which the organism is resistant, and requiring a high level of care in the usual living situation. When the number of prescriptions in hospital for ‘resistant’ antibiotics was included in the model, the risk was highest in those with 3 or more prescriptions. Diabetes, recurrent UTI, and female gender all had similar odds ratios of between 2 and 3, and other ORs did not change markedly when diabetes and recurrent UTI were excluded from the model (allowing the model to include the 34 people who had missing values on one of those). Hospital admission and age were not related to the risk of MDR E coli UTI independently of the other risk factors. In a further logistic regression model including only the 177 participants with data on catheterisation, the OR for catheterisation in the past year was 2.45 (95 % CI 1.0–5.9). ORs for other variables were not meaningfully different with catheterisation included or not included in the model (data not shown).

This case control study was performed to identify the local risk factors for acquisition of this MDR E. coli with a view to using the identified risk factors to target infection control and antimicrobial stewardship interventions In this small community AMR is rarely encountered however, with the emergence of MDROs worldwide and increasing travel within countries as well as internationally, the introduction of MDROs is an increasing risk to any geographical area [23]. Control of such outbreaks with antimicrobial stewardship and infection prevention and control are important strategies to slow the emergence of MDROs at a local, national and global level. In current healthcare environments this needs to be accomplished with minimal utilization of resources.

E.coli ST 131 is most commonly associated with community acquired infection [24], although more recently an association with healthcare and elderly patients has been described [25]. This association is mirrored in the outbreak setting in this study. The antimicrobial susceptibility of E. coli has been shown to vary geographically and this may be associated with residence in nursing homes [26].

Antimicrobials should be used only as necessary in treating frail elderly people, and infection control strategies such as hand and equipment hygiene are likely to be an important component of their care in hospital and in the community, to reduce the risk of future resistant UTIs. The major findings of this study illustrate the importance of all sectors of local healthcare on the transmission of MDROs, and that focusing on a single setting will not give maximal effect when implementing antimicrobial stewardship and infection prevention and control strategies to slow the transmission of these organisms.