Researchers identify rare resistance mutation in UTI bacterium

Researchers at the University of Florida have identified a rare mutation that causes resistance to the quinolone antibiotic levofloxacin in a bacterium associated with urinary tract infections (UTIs).

The bacterium, Ureaplasma parvum, was isolated from urine specimens of 180 college-age women who had first-time UTIs, which are common in women and account for more than 8 million healthcare visits a year. It's believed to be the first time the levofloxacin mutation has been detected in a U parvum isolate in the United States, researchers report in a study this week in Antimicrobial Agents and Chemotherapy.

While low levels of antibiotic resistance were found overall in the urine samples from the college-age women, the authors say the detection of a quinolone-resistance mutation is a concern because Ureaplasma species are already intrinsically resistant to penicillins and other beta-lactam antibiotics commonly used to treat UTIs. Antibiotic-resistant UTIs can complicate and prolong illness, restrict treatment options, and add to healthcare costs.

High Ureaplasma rates

The prospective cohort study, part of a larger study to determine risk factors for first-time UTI and development of recurrent UTIs, recruited 180 women with symptomatic first-time UTI and 80 age-matched controls. Thirty-five of the women in the UTI group had recurrent UTIs within a year of the initial infection.

The study is the first to evaluate antibiotic resistance in college-aged women with first-time UTIs. Nearly 20% of women ages 15 to 29 are diagnosed as having a UTI.

Although Escherichia coli was the most common UTI-causing pathogen isolated from the urine samples and is most frequently associated with UTIs, 113 women (63%) had Ureaplasma sppor its close relative, Mycoplasma hominis, isolated as a primary or secondary uropathogen. Ureaplasma and Mycoplasma species are members of a class of bacteria calledMollicutes, which are distinguished by the absence of a cell wall.

Even when clinicians send UTI samples for culture and susceptibility testing, many labs lack the capability to cultivate Ureaplasma and Mycoplasma species and don't test for them. But because many of the antibiotics used to treat UTIs are ineffective against these microbes, the authors explain, they can play a role in treatment failure, even when they are not the primary cause of symptoms.

"Antibiotics like penicillin and the other beta-lactamases that interfere with cell wall synthesis are totally useless against the Mollicutes," lead author Mary Brown, PhD, a professor of infectious diseases and immunology at the University of Florida's College of Veterinary Medicine, said in an American Society of Microbiology (ASM) press release. ASM publishes Antimicrobial Agents and Chemotherapy.

Overall, 60 U parvum, 13 U urealyticum, and 10 M hominis isolates were available for antibiotic susceptibility testing, and only 2 were identified as resistant to any of the three antibiotics with established breakpoints for resistance—levofloxacin, tetracycline, and erythromycin. One isolate was resistant to levofloxacin, and the other to tetracycline. Using polymerase chain reaction testing, the researchers identified both isolates as U parvum.

Molecular analysis detected the tetM gene, the most common gene associated with tetracycline resistance in Ureaplasma species, in one of the U parvum isolates. In the other, an S83W mutation within the parC gene was identified as the cause of the levofloxacin resistance. The only other reports of this mutation in a U parvum isolate are from Japan and China.

Periodic surveillance recommended

The authors note that in comparison with other studies that have evaluated antibiotic resistance in Ureaplasma in the United States, the resistance levels among the study population was low. For instance, two previous studies of clinical isolates of Ureaplasma obtained from either the adult urogenital tract or samples from neonates with respiratory infections found tetracycline resistance in 33% and 34% of samples, respectively.

The authors suggest the lower resistance levels found in their study could be because the college-age women were generally healthier and less likely to have conditions that would increase their likelihood for hospitalization and exposure to antibiotics. In addition, since the participants were reporting first-time UTIs, they had not been exposed to antibiotics specifically for UTI treatment.

But Brown says she's concerned that the isolate with the mutation also appeared to be resistant to ciprofloxacin, an indication that the mutation could cause resistance to other quinolone antibiotics, which would further limit treatment options for UTIs caused by U parvum and M hominis. And since sexual transmission is the primary transmission pathway for Ureaplasma spp and M hominis in adults, strains carrying the mutated gene could spread. Brown and her colleagues recommend that clinicians consider incorporating periodic surveillance for antibiotic resistance in these pathogens.

"Periodic surveillance can alert providers to changes in regional antibiotic resistance patterns, so they can adjust their empirical treatment selection accordingly to choose the most effective treatment," they write.

See also:

Aug 21 Antimicrob Agents Chemother abstract

Aug 21 ASM press release

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