Temocillin 1g powder for solution for injection vials

Background: The emergence of multidrug-resistant Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL) and AmpC-producing Enterobacterales, has brought renewed interest in temocillin, a narrow-spectrum β-lactam antibiotic first introduced in the 1980s. Objectives: We aimed to provide a comprehensive overview of the microbiological, pharmacological, and clinical profile of temocillin. Methods: We conducted a narrative review of the literature using the PubMed database to identify relevant studies concerning the microbiology, pharmacokinetics, pharmacodynamics, clinical applications, and safety of temocillin. Results: Temocillin shows strong in vitro activity against ESBL- and AmpC-producing organisms, and partial efficacy against certain Klebsiella pneumoniae carbapenemase (KPC)-producing strains. Its pharmacokinetic and pharmacodynamic characteristics, including β-lactamase stability and low ecological impact, support its use in urinary tract infections, bloodstream infections, intra-abdominal infections, pneumonia, and central nervous system infections. Additionally, evidence supports its utility in outpatient parenteral antimicrobial therapy (OPAT), including subcutaneous administration, and in vulnerable populations such as pediatric, elderly, and immunocompromised patients. Temocillin demonstrates a favorable safety profile, minimal disruption of gut microbiota, and cost-effectiveness. It also exhibits synergistic activity with agents like fosfomycin, further enhancing its clinical value. Most of the current evidence is derived from retrospective and observational studies. Conclusions: Temocillin emerges as a promising carbapenem-sparing option for the treatment of challenging infections caused by multidrug-resistant Gram-negative bacteria.

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Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current evidence on temocillin and its uses in infectious diseases. A search was run on PubMed using the terms (‘Temocillin’ [Mesh]) AND (‘Infection’ [Mesh]). Current knowledge regarding temocillin in urinary tract infection, blood-stream infections, pneumonia, intra-abdominal infections, central nervous system infections, skin and soft tissues infections, surgical sites infections and osteoarticular Infections were summarized. Temocillin retain a favourable profile on microbiota and risk of Clostridioides difficile infections and could be an option for treating outpatients. Temocillin may be a valuable tool to treat susceptible pathogens and for which a carbapenem could be spared. Other advantages in temocillin use are that it is well-tolerated; it is associated with a low rate of C. difficile infections; it is active against ESBL, AmpC, and KPC-producing Enterobacterales; and it can be used in the OPAT clinical setting.

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conferred a significant increase (from 8- to 16-fold) of the temocillin MIC. Altogether, we have shown that temocillin resistance in the ECC can result from a single BaeS alteration, likely resulting in the permanent phosphorylation of BaeR and leading to AcrD overexpression and temocillin resistance through enhanced active efflux.

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BACKGROUND: BaeS/BaeR is a two-component system of Escherichia coli that controls the expression of porins and efflux pumps. Its role in beta-lactam resistance is limited. OBJECTIVES: To study the role of baeS/baeR two-component system in temocillin resistance in E. coli. METHODS: E. coli strain BW25113 and single-gene deletion mutants related to two-component systems were collected from the KEIO collection. Double-gen deletion mutants were generated. Temocillin-resistant mutant frequencies were determined at 32 mg/L. E. coli BW25113 mutants were selected by selective pressure from serial passages. Biological costs were analysed by growth curves. Genomes of the generated mutants were sequenced. The expression level of the mdtA, mdtB, mdtC, acrD and tolC in the ΔbaeS mutant was determined by RT-PCR (with/without temocillin exposure). RESULTS: The frequency of temocillin mutants ranged from 2.12 × 10-8 to 4.51 × 10-8 in single-porin mutants. No mutants were recovered from E. coli BW25113 (>10-9). Selection of temocillin-resistant variants by serial passage yielded mutants up to 128 mg/L. Mutations were found in the baeS gene. Temocillin MICs ranged from 4 to 32 mg/L (highest MICs for ΔbaeS and ΔompR). The efflux pumps mdtA, mdtB, mdtC and acrD pumps were overexpressed 3-10-fold in the presence of temocillin in ΔbaeS compared to control. CONCLUSIONS: Mutations in the sensor histidine kinase, baeS, may be involved in temocillin resistance through the expression of the efflux pumps mdtABC and acrD. In addition, the low mutation rate may be a good predictor of temocillin activity.

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BACKGROUND: Temocillin is a narrow spectrum β-lactam active against MDR Enterobacterales. Mechanisms of acquired resistance to temocillin are poorly understood. We analysed resistance mechanisms in clinical isolates of Escherichia coli and evaluated their impact on temocillin efficacy in vitro and in a murine peritonitis model. METHODS: Two sets of isogenic clinical E. coli strains were studied: a susceptible isolate (MLTEM16S) and its resistant derivative, MLTEM16R (mutation in nmpC porin gene); and temocillin-resistant derivatives of E. coli CFT073: CFT-ΔnmpC (nmpC deletion), CFTbaeS-TP and CFTbaeS-AP (two different mutations in the baeS efflux-pump gene).Fitness cost, time-kill curves and phenotypic expression of resistance were determined. Temocillin efficacy was assessed in a murine peritonitis model. RESULTS: MICs of temocillin were 16 and 64 mg/L for MLTEM16S and MLTEM16R, respectively, and 8, 128, 256 and 256 mg/L for E. coli-CFT073, CFT-ΔnmpC, CFTbaeS-TP and CFTbaeS-AP, respectively. No fitness cost of resistance was evidenced. All resistant strains showed heteroresistant profiles, except for CFTbaeS-AP, which displayed a homogeneous pattern. In vitro, temocillin was bactericidal against MLTEM16R, CFT-ΔnmpC, CFTbaeS-TP and CFTbaeS-AP at 128, 256, 512 and 512 mg/L, respectively. In vivo, temocillin was as effective as cefotaxime against MLTEM16R, CFT-ΔnmpC and CFTbaeS-TP, but inefficient against CFTbaeS-AP (100% mortality). CONCLUSIONS: Heteroresistant NmpC porin alteration and active efflux modification do not influence temocillin efficacy despite high MIC values, unfavourable pharmacokinetic/pharmacodynamic conditions and the absence of fitness cost, whereas homogeneously expressed BaeS efflux pump alteration yielding similar MICs leads to temocillin inefficacy. MIC as sole predictor of temocillin efficacy should be used with caution.

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Abstract Objectives The aim of this study is to describe the real-life use of temocillin in bone and joint infections (BJI). Patients and methods We performed a monocentric retrospective study, including all patients treated by temocillin for a BJI due to extended spectrum β-lactamase-producing Enterobacterales (ESBL-E) between 1 January 2015 and 31 December 2022. Outcomes were evaluated at least 3 months after the end of antimicrobial treatment. Clinical cure was defined as the absence of recurrence of BJI during follow-up among patients who completed at least 7 days of temocillin. If the patient discontinued temocillin due to ineffectiveness, the outcome was considered to be unfavourable. Seventeen patients were treated with temocillin for ESBL-E associated BJI during the study period. Results Infections included osteomyelitis of the foot (7/17; 41.2%), femoral osteomyelitis (4/17; 23.5%), disco-vertebral infections (2/17; 11.8%), total knee prosthesis infections (2/17; 11.8%) and total hip prosthesis infections (2/17; 11.8%). All patients except one (n = 16) had surgical management of the infection. The main bacteria identified were the Enterobacter cloacae complex (n = 9) and Klebsiella pneumoniae (n = 5). The median daily dose was 6 g for a median duration of 42 days (IQR 14–42 days). The median duration of follow-up was 12 months (IQR 5.25–14.5). Overall, 12 patients completed at least 3 months of follow-up, and clinical cure was observed in eight of them (8/12; 66.7%). Conclusion So far, this is the first report of BJI successfully treated with temocillin. This suggests that temocillin may be an alternative to treat BJI involving difficult-to-treat Enterobacterales when oral therapy is not available.

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Objectives: Temocillin is an antibiotic belonging to the β-lactam family, introduced in 1988 but soon forgotten because of its narrow spectrum. Recently, it has been repurposed for its effectiveness against ESBL Enterobacteriaceae, and represents an alternative of choice to carbapenems due to its limited impact on the microbiota. Patient: We present here a successful case of antibiotic prophylaxis of recurrent ESBL urinary tract infections with subcutaneously administered temocillin. Conclusions: Temocillin is rarely administered subcutaneously and even more rarely in prophylactic situations. However, its tolerance profile and low impact on the microbiota should help reconsideration of its use in particular cases like this one.

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