ORIGINAL ARTICLE

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ANTIMICROBIAL SUSCEPTIBILITY OF COMMUNITY-ACQUIRED UROPATHOGENS IN GENERAL PRACTICE

A comparison of the results of the present study with the resistance rates previously published in this country but involving a more generalized bacteriological survey¹⁰, showed a broadly similar picture but with a few exceptions. In comparison to the earlier study by Cheong et al, our study showed broadly corresponding figures for resistance  rates of E. coli to ampicillin (62% versus 50%), to S-T (42% versus 34%), and to cefuroxime (0% for both) but considerably lower figure for amoxicillin-clavulanate (3.3% versus 18%) and higher figure for norfloxacin ( 8.8% versus 1.6%). The major weakness of our study was the relatively smaller sample size and the temporal limits, which did not allow us to make comments on the change of antimicrobial resistance with time.

Studies from the US and worldwide indicate the emergence of high level S-T resistance in a significant percentage (>20%) of community-acquired E. coli UTI isolates. Table 3 shows representative studies from various geographical areas. The data should be viewed in the context of a dynamic and changing pattern of antimicrobial susceptibility with time. High levels of resistance were already found in countries like India, Brazil and Nicaragua. Most parts of Europe, Canada, UK and parts of the USA have fairly low resistant levels. It is interesting to note that Japan has the lowest S-T resistant E. coli isolates in the world. The reason was that in Japan S-T was not licensed for use in uncomplicated cystitis and the drug was remarkably expensive. This attested to the fact that antibiotic use correlated with development of resistance. The local usage of S-T has been significant as it has been used for decades in this country. According to the Malaysian National Medicines Use Survey²² which tracks medication usage both in the public and private sectors, the total usage of S-T for the year 2004 was given as 0.6 Defined Daily Dose/1000 population/day 2004 (compare with cephalexin 1.2, cefuroxime 0.6, norfloxacin 0.1 and amoxicillin-clavulanate 3.0).

It is interesting to note that the complete genome sequences of E. coli strains, including one uropathogenic strain, is now available²³. The chromosomes of E. coli are highly diverse mosaic structures, consisting of a core genome of homogenous elements and a large flexible gene pool of mobile genetic elements.²⁴ The dynamic process of the E. coli genomes may then provide for continued emergence of new clones. The recent detection of a globally disseminated E. coli clone (clonal group A) accounting for up to 50% of S-T resistant cystitis and pyelonephritis isolates, may explain the increasing resistance pattern and indicates the need for ongoing surveillance.^25-27

Table 3: Antimicrobial resistance of E. coli to sulphamethoxazole-trimethoprim in community-acquired UTI

Studies of antimicrobial resistance form the basis for decisions on empiric therapy. Antimicrobial susceptibility of E. coli to S-T is pivotal, as it is the standard first-line antibiotic for UTI. Both the local studies (by Cheong et al and the present one) clearly showed that E. coli is now resistant to ampicillin in >50% of cases and to S-T in >30% of cases. Assuming that these figures are more broadly applicable, then it will be time for us to seriously reconsider the empiric use of these antibiotics in our country, or to seriously investigate at which level the outcome of therapy with these antibiotics is influenced, or to develop strategies to counteract further resistance development to these antibiotics.

The Infectious Disease Society of America has published evidence-based guidelines for the treatment of acute uncomplicated cystitis in women. They recommended the use of a 3 day course of S-T as empiric first-line treatment except in communities with high rates of resistance (>10-20%) to S-T among uropathogens.³⁶ Subsequently Le and Miller conducted a decision and cost analysis to determine the resistance rate at which S-T should not be used in favour of a quinolone antibiotic. Their results indicated that, when the S-T resistance in a community exceeds 22%, empiric fluoroquinolone therapy becomes less costly than S-T therapy. The added costs of reinfection and complications from progression of infection when using S-T, makes quinolone the antibiotic of choice.³⁷ However, this analysis did not take into account the concerns about the promotion of resistance to the quinolones. In fact, organisations like the Canadian Family Physicians38 and the Scottish Intercollegiate Guidelines Network (SIGN Guidelines 2006)³⁹ recommended against quinolones as first-line agents, with the latter stating that quinolones should not be used for empiric treatment of lower UTI. Favourable outcomes would also require some degree of physician adherence to these guidelines⁴⁰.

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