Pivmecillinam 200mg tablets

BACKGROUND: Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%. METHODS AND FINDINGS: This was a randomized, controlled, double-blind non-inferiority trial. We recruited patients from 16 sites in a general practice setting in Norway, Sweden, and Denmark. Non-pregnant women aged 18-60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016. Patients with informed consent were randomized (1:1 ratio) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days. The patient, treating physician, and study personnel were blinded to treatment allocation. The primary outcome was the proportion of patients who felt cured by day 4, as assessed from a patient diary. Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis. A total of 383 women were randomly assigned to treatment with either ibuprofen (n = 194, 181 analyzed) or pivmecillinam (n = 189, 178 analyzed). By day 4, 38.7% of the patients in the ibuprofen group felt cured versus 73.6% in the pivmecillinam group. The adjusted risk difference with 90% confidence interval was 35% (27% to 43%) in favor of pivmecillinam, which crossed the prespecified non-inferiority margin. Secondary endpoints were generally in favor of pivmecillinam. After 4 weeks' follow-up, 53% of patients in the ibuprofen group recovered without antibiotic treatment. Seven cases of pyelonephritis occurred, all in the ibuprofen group, giving a number needed to harm of 26 (95% CI 13 to 103). Five of these patients were hospitalized and classified as having serious adverse events; 2 recovered as outpatients. A limitation of the study was the extensive list of exclusion criteria, eliminating almost half of the patients screened. We did not register symptoms in the screening process; hence, we do not know the symptom burden for those who declined to participate. This might make our results less generalizable. CONCLUSIONS: Ibuprofen was inferior to pivmecillinam for treating uncomplicated UTIs. More than half of the women in the ibuprofen group recovered without antibiotics. However, pyelonephritis occurred in 7 out of 181 women using ibuprofen. Until we can identify those women who will develop complications, we cannot recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01849926 EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14.

Abstract licence: CC BY

The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions. These studies revealed a benign safety and tolerability profile, awareness of which will inform treatment decisions as pivmecillinam is made available in the United States. Together with the evidence for efficacy of, and minimal resistance to, pivmecillinam, the findings of this review support the position of pivmecillinam as a first-line treatment for uUTI.

Abstract licence: CC BY

We thank Dr. Sfeir for his valuable contributions [1] in response to our systematic review of the safety and tolerability of pivmecillinam [2].We are grateful for his acknowledgment of our findings, which revealed a benign safety profile based on extensive clinical data.We concur with his opinion that the 2024 approval of pivmecillinam by the US Food and Drug Administration (FDA)-for treatment of uncomplicated urinary tract infection (uUTI) caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus in women aged 18 years-marks a positive advancement [2, 3].Dr. Sfeir's point regarding the need for comprehensive susceptibility testing to support the efficacy of pivmecillinam, while outside the scope of the original article, is a good one.Clearly, the availability of pivmecillinam will necessitate updates to testing procedures in US clinical microbiology laboratories.However, he also comments that the Clinical and Laboratory Standards Institute (CLSI) has not yet established breakpoints for pivmecillinam.It is important to understand that breakpoints should be defined for the active form, mecillinam, rather than the

Abstract licence: CC BY

BACKGROUND: In the first months after cystectomy, the most frequent cause of readmission is infection from the urinary tract. Nonetheless, current guidelines are unable to provide evidence-based recommendations on preventative measures and, as a result, antibiotic prophylaxis varies across surgical centres. Most centres in Denmark administer empiric antibiotic prophylaxis at ureteral stent removal after cystectomy, where infection rates peak. However, data indicates that the postoperative urinary microbiota is composed of a wide range of bacteria, suggesting that the patients may benefit from an individualised approach. This trial aims to test whether targeted postoperative antibiotic prophylaxis can reduce infection-related readmissions after cystectomy compared to the current empiric approach. METHODS: We present a multicentre, open-label, superiority, randomised clinical trial using a group-sequential design. Participants will be randomly assigned with a 1:1 allocation ratio to receive one of two orally administered single-day antibiotic treatments on the day of ureteral stent removal: (a) standard-of-care pivmecillinam 400 mg morning, noon, and evening or (b) antibiotics targeted to the microbiota identified in a postoperative urine sample. The primary endpoint is the infection-related readmission rate after 90 postoperative days. Secondary endpoints include complication and readmission rates, days alive and out of hospital, quality of life, and microbiological isolates in the urine and blood and antimicrobial susceptibility analyses. A total of 248 patients are planned to be enrolled. The sample size is based on a hypothesised absolute risk reduction in the infection-related readmission rate from 29 to 14%, corresponding to a number needed to treat of six to reduce one hospital readmission. A group-sequential design is proposed to allow for early stopping at interim analysis after 50% enrolment based on predefined rules. DISCUSSION: Responsible use of antibiotics is gaining increasing importance globally, and proper prophylactic strategies amongst high-risk patients are essential to avoid hospital admissions with administration of broad-spectrum agents. In this protocol, we present the first randomised clinical trial testing whether individualised targeted antibiotics can reduce the risk of infections after cystectomy. Results of the trial may improve recovery for this vulnerable patient group, while also potentially improving antibiotic stewardship. TRIAL REGISTRATION: EU trial number 2024-514312-27-00. Registered on December 10, 2024. CLINICALTRIALS: gov NCT06709196. Registered on November 27, 2024.

Abstract licence: CC BY-NC-ND

OBJECTIVE: To review the evidence and discuss use of pivmecillinam in uncomplicated acute cystitis. DATA SOURCES: A literature search was conducted utilizing PubMed (from 2000 through August 2024) and ClinicalTrials.gov. Medical Subject Headings (MeSH) terms, such as mecillinam or pivmecillinam and urinary tract infections, were utilized. Additional references were identified by reviewing literature citations. STUDY SELECTION AND DATA EXTRACTION: Articles were limited to English language publications evaluating the efficacy or safety of pivmecillinam for urinary tract infections (UTIs) in adult populations. DATA SYNTHESIS: Data from 6 randomized controlled trials support pivmecillinam for acute uncomplicated cystitis at doses of 200 to 400 mg 3 times daily for 3 to 7 days, with more consistent clinical and bacteriologic cure observed with 400 mg doses and longer therapy durations. Clinical evaluation of 400 mg 2 to 3 times daily is available with use more common in non-US Food and Drug Administration (FDA)-approved populations, such as men, pregnancy, and multidrug resistant infections. There are limited data supporting pivmecillinam for pyelonephritis; routine use is cautioned until further clinical data are available.Relevance to patient care and clinical practice in comparison with existing drugs:As resistance to first-line antimicrobials rises, the need for safe and effective treatment options remains high. Pivmecillinam represents a new therapeutic option available in the United States for outpatient management of uncomplicated acute cystitis. CONCLUSION: Pivmecillinam could be a key agent for uncomplicated acute cystitis. Utilization will likely be cost driven, but the promise of low resistance encourages the place in therapy when other agents are not susceptible to infecting uropathogens.

Abstract licence: CC BY-NC-SA

BACKGROUND: Patients with urinary tract infection (UTI) in German outpatient care are usually treated by general practitioners (GPs), as well as by other specialties. To prevent antibiotic resistances and side effects, German guidelines recommend fosfomycin, nitrofurantoin, pivmecillinam and nitroxoline as first-line treatments, and advice against broad-spectrum antibiotics such as fluoroquinolones and cephalosporins. However, data from the European Centre for Disease Prevention and Control indicates a significant proportion of second-line antibiotics in German outpatient care. Our aim was to analyze whether antibiotic prescription has changed over time in accordance with guidelines. In addition, we aimed to investigate whether specialties prescribe different antibiotics for UTIs and whether prescription varies according to patient age and sex. For patients receiving more than one antibiotic, we wanted to determine whether subsequent prescriptions show a change in substances and specialties involved. METHODS: This retrospective study involved routine data (2013 to 2019) provided by the Bavarian Association of Statutory Health Insurance Physicians. Data on diagnoses and prescriptions were transmitted from outpatient care physicians on a quarterly basis. UTI patients ≥12 years were included. RESULTS: We analyzed 1.7 million UTI prescription cases. In females, shares of fluoroquinolones decreased sharply over time, while shares of first-line substances fosfomycin and pivmecillinam increased. Gynecologists showed the highest shares of first-line substances compared to GPs and urologists. Fluoroquinolone shares decreased in all three specialty groups. In females, older patients showed lower shares of first-line substances than younger patients. If a second or third antibiotic was prescribed, fosfomycin shares decreased, while shares of nitrofurantoin, nitroxoline and cephalosporins increased. CONCLUSIONS: Our findings show a trend towards a more guideline-adherent prescribing in the treatment of UTI, with a significant increase of shares of fosfomycin and pivmecillinam, especially in women, and a sharp decrease of shares of fluoroquinolones.

Abstract licence: CC BY