pivmecillinam
Sources réglementaires consultées
Indications approuvées
- Cystite aiguë non compliquée due à des bactéries sensibles au mécillinam chez l’adulte.
Contre-indications
Absolues
- Hypersensibilité au pivmécillinam, au mécillinam, aux pénicillines, aux céphalosporines ou aux excipients.
- Trouble entravant le transit œsophagien.
- Déficit du transporteur de la carnitine, acidurie méthylmalonique ou acidémie propionique.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer une hypersensibilité sévère ou une anaphylaxie. Rechercher tout antécédent de réaction immédiate aux bêta-lactamines avant l’emploi et arrêter en cas de réaction allergique. — CIMA/AEMPS, ficha técnica 81499
- Mise en garde majeure · Il peut provoquer une diarrhée associée à Clostridioides difficile pendant ou après le traitement ; évaluer toute diarrhée importante et éviter les antipéristaltiques si une colite est suspectée. — CIMA/AEMPS, ficha técnica 81499
- Mise en garde majeure · Avaler le comprimé avec au moins un demi-verre de liquide afin d’éviter sa rétention œsophagienne et une ulcération. — CIMA/AEMPS, ficha técnica 81499
- Mise en garde majeure · Éviter les traitements prolongés ou répétés en raison du risque de déficit en carnitine ; éviter en cas de porphyrie et arrêter en cas de réaction cutanée sévère. — CIMA/AEMPS, ficha técnica 81499
- Mise en garde majeure · Une exposition maternelle proche de l’accouchement peut entraîner un faux positif d’acidémie isovalérique au dépistage néonatal ; informer l’équipe néonatale. — CIMA/AEMPS, ficha técnica 81499
Interactions médicamenteuses
- ModéréeProbénécide
Mécanisme: Il réduit la sécrétion tubulaire rénale et peut augmenter et prolonger l’exposition à l’antibiotique.
Recommandation: Éviter l’association sauf indication délibérée et surveiller la toxicité.
CIMA/AEMPS, ficha técnica 81499
- SévèreAcide valproïque, valproate et autres médicaments libérant de l’acide pivalique
Mécanisme: Ils augmentent le risque de déficit en carnitine.
Recommandation: Éviter l’association.
CIMA/AEMPS, ficha técnica 81499
- ModéréeAntibiotiques bactériostatiques
Mécanisme: Ils peuvent antagoniser l’action bactéricide du mécillinam.
Recommandation: Éviter l’association si possible.
CIMA/AEMPS, ficha técnica 81499
Effets indésirables
Communs (≥1%)
Nausées, diarrhée et éruption cutanée
Rares mais graves
Anaphylaxie, colite à C. difficile et cytopénies sévères
Grossesse et allaitement
Il peut être utilisé pendant la grossesse lorsqu’il est cliniquement indiqué et pendant l’allaitement. En cas d’utilisation proche de l’accouchement, signaler le risque de faux positif d’acidémie isovalérique au dépistage néonatal.
Bibliographie récente (PubMed)
Urinary tract infections (UTIs) are associated with 25-40% of antibiotics consumed in primary care and are, therefore, driving antibiotic resistance. The worldwide increase in antibiotic resistance especially in Escherichia coli has complicated the treatment choices for UTIs and absence of effective oral antibiotics may lead to increasing need for more effective treatments. In this review we focus on the importance of the correct diagnosis of UTI as based on proof of urinary pathogens in the urine and discuss diagnostic measures including microscopy, dipstick, and culture. Antibiotic treatment can often await diagnostic measures with pain relief such as ibuprofen. The risk of an uncomplicated UTI leading to pyelonephritis is low (1-2%) and presence of bacteria in the bladder leaves some time for the immune system to react. Three antibiotics are recommended as based on their activity, and low propensity to select for resistance, i.e. nitrofurantoin, fosfomycin, and pivmecillinam, and in general, 3-5 days of treatment will suffice. Understanding the usual benign course of uUTIs can help reduce antibiotic treatment in many cases, e.g. starting treatment by pain relief and awaiting the course of infection without antibiotics. Better rapid tests in primary care are urgently needed to enforce such policies.
Most guidelines recommend nitrofurantoin, fosfomycin, and sometimes pivmecillinam for uncomplicated urinary tract infections (UTIs), but direct comparisons between these antibiotics are needed. This study evaluated the effectiveness and safety of a single dose of fosfomycin compared with two doses of fosfomycin and short-course regimens of nitrofurantoin and pivmecillinam in women with UTI symptoms. This phase 4, pragmatic, multicentre, parallel-group, open-label, randomised clinical trial was conducted in Spanish primary care centres from 2022 to 2024. Women aged 18 years or older with at least one UTI-specific symptom (dysuria, urinary urgency, urinary frequency, or suprapubic tenderness) and a positive urine dipstick test for either nitrites or leukocyte esterase were randomly assigned (1:1:1:1) to one of four treatments: a single 3 g dose of fosfomycin, two 3 g doses of fosfomycin, nitrofurantoin (100 mg three times per day for 5 days), or pivmecillinam (400 mg three times per day for 3 days). Doctors and patients were not masked to group assignment. The primary outcome was the proportion of patients with clinical resolution (defined as the disappearance of all infection symptoms) at day 7. This trial is registered with ClinicalTrials.gov (NCT04959331) and EudraCT (2021-001332-26) and is completed. Of the 804 patients assessed for eligibility between April 4, 2022 and Nov 14, 2024, 768 patients were randomly allocated (191 to the single-dose fosfomycin group, 194 to the two-dose fosfomycin group, 190 to the nitrofurantoin group, and 193 to the pivmecillinam group). Patients had a median age of 48 years (IQR 34-63). Race and ethnicity data were not collected. Among the 720 women with available data included in the primary analysis, single-dose fosfomycin had the lowest proportion of clinical resolution (109 [59%] of 185 patients), while nitrofurantoin had the highest (128 [74%] of 172 patients; difference 15·5 percentage points [95% CI 5·9 to 25·1] vs single-dose
Antibiotic resistance occurs when microorganisms resist the drugs used against the infection caused by them and neutralize their effects over time using various mechanisms. These mechanisms include preventing drug absorption, changing drug targets, drug inactivating, and using efflux pumps, which ultimately cause drug resistance, which is named pan-drug-resistant (PDR) infection if it is resistant to all antimicrobial agents. This type of drug resistance causes many problems in society and faces the health system with difficulties; therefore their treatment is crucial and encourages doctors to develop new drugs to treat them. PDR Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli are among the most significant resistant bacteria to many antimicrobial agents, and only a limited range of antibiotics, especially synergistically are effective on them. For the therapy of PDR A. baumannii, tigecycline in combination with colestimethate, imipenem, amikacin, and ampicillin-sulbactam are the most effective treatments. The utilization of β-lactamase inhibitors such as ceftolozane-tazobactam, ceftazidime-avibactam, or imipenem-cilastatin-relebactam has the most efficacy against PDR P. aeruginosa. The PDR K. pneumoniae has been treated in the last decades with tigecycline and colistin, but currently, nitrofurantoin, fosfomycin, and pivmecillinam seem to be the most effective agent for the therapy of PDR E. coli. While these drugs impressively struggle with PDR pathogens, due to the daily increase in antibiotic resistance in microorganisms worldwide, there is still an urgent need for the expansion of novel medicines and methods of combating resistance.
Pivmecillinam is the oral prodrug of mecillinam. Following absorption, the pivaloyl ester is hydrolyzed, releasing the active mecillinam into systemic circulation. It is a narrow spectrum amidino(penicillin) antibiotic with activity against the main uropathogens. Pivmecillinam has been used for decades in the Nordic countries as one of the main drugs for uncomplicated urinary tract infection (uUTI) with resistance levels in Escherichia coli remaining around 5%. A literature search was performed via PubMed during January-February 2026. The review centers on a brief mention of the mechanism of action, resistance mechanisms, pharmacokinetics, pharmacokinetic/pharmacodynamics, adverse effects, and clinical use. Pivmecillinam is stable against many broad-spectrum beta-lactamases increasing its versatility as an empiric antibiotic. The main indication is uUTI, but it is also used for treatment of acute pyelonephritis. The review addresses clinical experience, dose and duration of treatment with suggestions for dosing recommendations. There remains some debate on the ideal dose and duration of treatment. Pivmecillinam can also be used for treatment of some bacterial diarrhea types. Pivmecillinam can play an important role as empiric and directed treatment for UTIs due to its beneficial antibacterial spectrum against common uropathogens, stability toward beta-lactamases, minor effect on microbiomes and general safety.