‘Forgotten Antibiotic’ Better Than Cefotaxime in Febrile UTIs?

In adults with febrile urinary tract infection (UTI), use of a “forgotten antibiotic” called temocillin led to less disruption of the intestinal tract microbiota than cefotaxime, with significantly lower Enterobacterales percentages, according to a study report in The Lancet Infectious Diseases. Vulnerability to third-generation cephalosporins was likewise decreased in patients receiving temocillin.
The rich commensal microbiota of the distal gut is a breeding ground for resistant microorganisms, and security damage to the human microbiota can happen with usage of antibiotics. The studys objective was to evaluate temocillin use with respect to intestinal tract colonization with third-generation cephalosporin-resistant pathogens.

Dr Håkan Hanberger

Mean patient age was 72.5 years and 54% were female. Analysis revealed less disruption of the intestinal microbiota in the temocillin group, with the composite primary endpoint fulfilled in 18 (26%) of 68 participants receiving temocillin, and in 30 (48%) of 62 clients getting cefotaxime (danger difference– 22%; 95% CI,– 42% to– 3%).

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An additional benefit of temocillin use would be decreased choice of resistant intestinal germs in healthcare facilities, lowering hospital-related infections from resistant bacteria. Hanberger included, “Recent studies of bacteremia due to Enterobacterales have actually shown that it is possible to reduce the treatment duration from 14 to 7 days.” Randomized controlled trials are warranted to find the minimum length of IV treatment required for febrile UTI among women and guys, he stated.

They were arbitrarily assigned 1:1 to either 2 g of temocillin (n = 77) or 1-2 g of cefotaxime (n = 75), both offered every 8 hours (open label, but masked to those performing microbiological analyses). Unfavorable occasion rates were similar: 52% in the temocillin group and 45% in the cefotaxime groups. Serious negative events occurred in 4% of the patients receiving temocillin and 1% receiving cefotaxime. He likewise wondered whether, with febrile UTI or pyelonephritis being often self-limiting, could a single dosage of temocillin or a third generation cephalosporin be enough? An extra benefit of temocillin use would be reduced selection of resistant digestive tract bacteria in hospitals, reducing hospital-related infections from resistant bacteria.

” We need oral stepdown antibiotics with impacts on pyelonephritis/febrile UTI with less ecological disruptions than those currently used,” Hanberger informed Medscape Medical News. “Or we need to utilize IV treatment with low environmental effect for the entire course.”.

Analysis of the microbiota showed a considerably lower percentage of Enterobacterales in the temocillin group vs the cefotaxime group with lowered vulnerability to third generation cephalosporins (P =.0049). While digestive tract colonization by toxin-producing C difficile after intravenous research study drug treatment was detected in 3 patients receiving temocillin and in 1 client getting cefotaxime, none of these established C difficile infections.
Unfavorable occasion rates were similar: 52% in the temocillin group and 45% in the cefotaxime groups. Serious negative occasions happened in 4% of the clients receiving temocillin and 1% receiving cefotaxime. The most typical unfavorable events were diarrhea and abdominal discomfort.
Given the comparable security and bacteriological efficacy of temocillin and cefotaxime with less intestinal tract microbiota disturbance for temocillin, the authors concluded, “Our findings show that temocillin is an ecologically beneficial alternative to cefotaxime in the treatment of febrile UTIs.”.
In an accompanying editorial, Cees van Nieuwkoop, MD, PhD, Department of Internal Medicine, Haga Teaching Hospital, The Hague, the Netherlands questioned the importance of the findings at the patient level, provided that the gut microbiota distinctions between temocillin and cefotaxime lessened rapidly and were no longer substantial at the end of antibiotic therapy. Brief follow-up avoided the evaluation of results of therapy on recurrent UTI or other interfered with gut microbiota sequelae.

The randomized, multicenter, superiority, open-label stage 4 trial was conducted among 152 adult patients admitted to 12 Swedish medical facilities and treated for thought or diagnosed febrile UTI (complicated or uncomplicated), including pyelonephritis. All had indicators for intravenous antibiotic treatment.
They were randomly assigned 1:1 to either 2 g of temocillin (n = 77) or 1-2 g of cefotaxime (n = 75), both provided every 8 hours (open label, however masked to those performing microbiological analyses). Patients were dealt with for 7-10 days (14 in the existence of bacteremia), with a minimum of 3 days on the study drug, with a switch to oral agents (ciprofloxacin, cefixime, co-trimoxazole, or ceftibuten) enabled subsequent to enhancement. Colonization was identified through rectal swabs.
The composite primary result was colonization with Enterobacterales with decreased susceptibility to third generation cephalosporins, or colonization with toxin-producing C. difficile, or both. It was evaluated after discontinuation of the intravenous research study drug, however prior to step-down to oral treatment was initiated.

He likewise wondered whether, with febrile UTI or pyelonephritis being often self-limiting, could a single dosage of temocillin or a 3rd generation cephalosporin be enough? The challenge would then be to discover which clients need extended antibiotic treatment and which do not.

Lancet Infect Dis. Published Online October 28, 2021. Abstract, Editorial.

” This is an intriguing paper,” Van Nieuwkoop stated in an interview with Medscape Medical News, “but in my opinion it does not alter the existing routine treatment practice of febrile UTI. Nevertheless, in locations with a high occurrence of resistant uropathogens, temocillin is an excellent alternative to spare carbapenems.”.

The study authors and Van Nieuwkoop have actually revealed no relevant monetary relationships.

The authors, led by Håkan Hanberger, MD, Linköping University, Linköping, Sweden, kept in mind that the increasing prevalence of third-generation cephalosporin-resistant E coli infections has resulted in utilize of carbapenems and an increased threat of multidrug-resistant Enterobacterales and C difficile infection. Since cefotaxime and other third-generation cephalosporins are associated with greater choice risk for antimicrobial resistance, alternative prescription antibiotics have been sought. In empirical treatment of febrile UTIs, temocillin– which has a narrow spectrum and showed low C difficile infection risk relative to cephalosporins and carbapenems– may be an alternative that is less vulnerable to disrupting the digestive tract microbiota..

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