One-day prevalence of asymptomatic carriage of toxigenic and non-toxigenic Clostridioides difficile in 10 French hospitals.

BACKGROUND: Asymptomatic faecal carriage of Clostridioides difficile has been widely evaluated, but its prevalence across a wide range of clinical departments and related risk factors are not well described. The objectives of the PORTADIFF study were to evaluate the prevalence and identifying risk factors leading to asymptomatic carriage of both toxigenic and non-toxigenic C. difficile. METHODS: The PORTADIFF study was a 1-day prevalence study carried out in 10 different French hospitals. Adult patients, who agreed to participate, were included in this study and provided a fresh stool sample. C. difficile strains isolated from carriage were characterized by polymerase chain reaction (PCR) detection of tcdA, tcdB, cdtA and cdtB, and PCR ribotyping. RESULTS: In total, 721 patients were included in this study. The median age was 73 years (range 18-101 years) and the male/female ratio was 1.06. C. difficile (either toxigenic or non-toxigenic strains) was isolated from 79 (11%) patients; 42 (5.8%) strains were toxigenic. The prevalence rates of asymptomatic carriage ranged from 5% on surgical wards to 19% on long-term care wards. The main risk factors associated with asymptomatic carriage were antibiotic treatment within the preceding 3 months (81.8% vs 53.7%; P<0.01), hospitalization within the preceding 2 months (55.8% vs 33%; P<0.01), cumulative duration of hospital stay before study inclusion (mean 50.1 vs 34.5 days; P<0.047), and hospitalization on a ward with high global incidence of C. difficile infection. CONCLUSION: Eleven percent of hospitalized patients were asymptomatic carriers of toxigenic or non-toxigenic C. difficile, and may constitute a potential reservoir of C. difficile strains.

Rapid diagnostic tests for infectious diseases in the emergency department.

BACKGROUND: Rapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed, although not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management. OBJECTIVES: The aim of this narrative review was to provide an overview of currently available RDTs for infectious diseases in the ED. SOURCES: PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the US Food and Drug Administration (FDA) or Conformité Européenne (CE) in vitro diagnostic devices with data on clinical samples, ability to run on fully automated systems and result delivery within 2 hours. CONTENT: A nonexhaustive list of representative commercially available FDA- or CE-approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in returning travellers and sexually transmitted infection, including HIV. The performance of tests was described on the basis of clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies. IMPLICATIONS: Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED work flow should be preplanned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical effectiveness and cost-effectiveness.

[Urinary tract infections in adults: Comparison of the French and the European guidelines]. / Infections urinaires de l'adulte : comparaison des recommandations françaises et européennes. Par le Comité d'infectiologie de l'Association française d'urologie (CIAFU).

INTRODUCTION: Acute urinary tract infections (UTIs) in adult are now a major public health issue in terms of morbidity, mortality and in terms of costs for society. The latest French guidelines and the European Association of Urology guidelines differ in some points. The aim of this article is to compare the guidelines of these two societies in order to highlight their differences but also their common points in the management of UTIs. METHODS: A comparative analysis of the latest French and European guidelines was carried out. The authors defined the following sub-sections: terminology, pyelonephritis, male UTIs, pregnancy urinary tract infections and cystitis. RESULTS AND CONCLUSION: The guidelines of these two societies are not very different in terms of diagnostic and therapeutic management. The major differences are in the duration of antibiotic therapies, where French guidelines continue to recommend long term treatments where EAU sometimes recommends only 5 days of antibiotics, as in the case of simple acute pyelonephritis. LEVEL OF EVIDENCE: 3.

Emerging extensively drug-resistant bacteria (eXDR) in France in 2018.

OBJECTIVE: This 2018 report of Healthcare-Associated Infections Early Warning and Response System (HAI-EWRS) notifications of carbapenemase-producing Enterobacteriaceae (CPE) or glycopeptide-resistant Enterococcus faecium (GRE), and of strains analysed by the National Reference Center for anti-microbial resistance (NRC) aimed to describe the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France and control measures implemented in hospital settings. PATIENTS AND METHODS: All HAI-EWRS notifications of eXDR received at the national level and all eXDR strains received at the NRC between January 1, 2018 and January 31, 2018 were analysed. Variables analysed were number of cases, number of strains, resistance mechanism, sample type, link with a foreign country, and control measures implemented. RESULTS: In 2018, 1704 CPE notifications and 315 GRE notifications were reported in France, with an increasing trend since 2012 (×6 for CPE, ×3 for GRE), from respectively 364 and 155 hospitals (+66% for CPE, +57% for GRE since 2012). eXDR strains were mainly isolated from rectal screening swabs. Notifications with patients receiving standard precautions were more often associated with outbreaks than notifications with patients receiving contact precautions at admission. NRC received 2674 CPE strains and 775 GRE strains in 2018 (×8.3 and ×2.8 compared with 2012). CONCLUSION: The increasing annual number of eXDR notifications and eXDR strains received by the NRC is multifactorial but reflects a worrying spread of eXDR in France. The number of infections remains low, but this article shows that existing recommendations are not fully implemented.

Perioperative infectious risk in urology: Management of preoperative polymicrobial urine culture. A systematic review. By the infectious disease Committee of the French Association of urology.

INTRODUCTION: The aim was to assess the risk of postoperative infections in patients with preoperative polymicrobial urine culture and to provide the urologist with practices to minimise the risk of infection in these clinical situations. METHODS: A systematic literature review was carried. All national and international recommendations have been reviewed. Data collection has been performed from the Cochrane, LILACS and the Medline database. 31 publications were selected for inclusion. RESULTS: Risk of infection in patients without ureteral stents or urinary catheters with previous polymicrobial urine culture is low. In the absence of leukocyturia, the urine sample can be considered as sterile. With ureteral stents or urinary catheters, the colonisation by biofilm ranges from 4 to 100% depending on the duration and ureteral stents or urinary catheters type. Urine culture is positive 24 to 45% of the time when ureteral stents or urinary catheters are known to be colonised. The post-operative risk of infection in endo-urological surgery in a patient with ureteral stents or urinary catheters is estimated around 8 to 11% depending on the type of surgery. A retrospective study reports a postoperative infections rate of 18.5% in photo selective vaporization of the prostate with preoperative polymicrobial urine culture. CONCLUSIONS: Scientific data are limited but for patients without ureteral stents or urinary catheters, in the absence of leukocyturia, the polymicrobial urine culture can be considered as negative. Considering a preoperative polymicrobial urine culture as sterile in patients with colonised ureteral stents or urinary catheters is at risk of neglecting a high risk of postoperative infections or sepsis even in case of perioperative antibiotic prophylaxis. It should not always be considered sterile and therefore, a perioperative antibiotic therapy could be an acceptable option.

Activity of fosfomycin alone or combined with temocillin in vitro and in a murine model of peritonitis due to KPC-3- or OXA-48-producing Escherichia coli.

Background: Alternative therapeutic regimens are urgently needed against carbapenemase-producing Enterobacteriaceae. Fosfomycin often remains active against KPC and OXA-48 producers, but emergence of resistance is a major limitation. Our aim was to determine whether the association of temocillin with fosfomycin might be useful to treat KPC- or OXA-48-producing Escherichia coli infections. Methods: Isogenic derivatives of E. coli CFT073 with blaKPC-3- or blaOXA-48-harbouring plasmids (named CFT073-KPC-3 and CFT073-OXA-48, respectively) were used. The addition of temocillin to fosfomycin was tested using the chequerboard method and time-kill curves as well as in a fatal peritonitis murine model. Mice were treated for 24 h with fosfomycin alone or in combination with temocillin. Bacterial loads, before and after treatment, were determined in the peritoneal fluid and fosfomycin-resistant mutants were detected. Results: Temocillin MICs were 8, 32 and 256 mg/L for CFT073 (WT), CFT073-KPC-3 and CFT073-OXA-48, respectively. Fosfomycin MIC was 0.5 mg/L for all strains. The chequerboard experiments demonstrated synergy for all three strains. In time-kill curves, combining temocillin with fosfomycin was synergistic, bactericidal and prevented emergence of resistance for CFT073-pTOPO and CFT073-KPC-3, but not CFT073-OXA-48. In vivo, for the three strains, bacterial counts were lower in peritoneal fluid with the combination compared with fosfomycin alone (P < 0.001) and inhibited growth of resistant mutants in all cases. Conclusions: The combination of fosfomycin and temocillin demonstrated a benefit in vitro and in vivo against E. coli strains producing KPC-3 or OXA-48-type carbapenemases. This combination prevented the emergence of fosfomycin resistance and proved to be more bactericidal than fosfomycin alone.

Towards precision medicine in sepsis: a position paper from the European Society of Clinical Microbiology and Infectious Diseases.

BACKGROUND: Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. AIMS: To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. SOURCES: A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. CONTENT: The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). IMPLICATIONS: A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways.

Comparison of MALDI-ToF MS with the Rapidec Carba NP test for the detection of carbapenemase-producing Enterobacteriaceae.

Although carbapenemase-producing Enterobacteriaceae (CPE) have become a serious public health issue, their detection remains challenging. The aim of this study was to implement a test based on imipenem hydrolysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS), using 65 strains producing or not a carbapenemase. Then, we compared its performance to that of the Rapidec Carba NP test using 20 additional strains. The MS-based test effectively discriminated between CPE and other non-carbapenem-susceptible strains compared to the Rapidec Carba NP test (sensitivity 100% and 92%, specificity 94% and 92%, respectively). The MS-based test gave less difficulty in interpretation than the colorimetric Rapidec Carba NP test. MALDI-ToF gave a result in less than one hour and limited the use of expensive molecular assays. In conclusion, the hydrolysis test based on MALDI-ToF MS can detect clinically relevant CPE isolates in routine practice. This technology, also described to screen for carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii complex strains, also seems to be interesting in routine practice for these pathogens.

Carriage of ESBL-producing Enterobacteriaceae in French hospitals: the PORTABLSE study.

BACKGROUND: Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage. METHODS: A point prevalence study was conducted in five different types of hospital ward [medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric] in eight French hospitals. All patients included in the study provided a fresh stool sample. RESULTS: In total, 554 patients were included in the study, with a median age of 73 years (range 60-82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%). CONCLUSION: The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.

Biological cost of fosfomycin resistance in Escherichia coli in a murine model of urinary tract infection.

Prevalence of fosfomycin resistance in E. coli clinical isolates from UTIs remains very low. Our hypothesis was that fosfomycin resistance may be associated with a biological cost. Three groups of strains of E. coli belonging to the B2 phylogenetic group were used: clinical wild-type (WT) isolates, clinical multidrug-resistant isolates and in vitro fosfomycin-resistant derivatives from the uropathogen clinical strain E. coli CFT073. In each group fosfomycin-susceptible and -resistant isolates were compared. In vitro, we found a significantly decreased growth rate for fosfomycin-resistant strains as compared with susceptible strains in the WT group. In a murine model of ascending UTI, there was a significant reduction in infection rates with fosfomycin-resistant isolates as compared with susceptible ones, in all 3 study groups, ranging from 28 to 39% (P<0.03). All fosfomycin-susceptible clinical strains were virulent in vivo (13/13), while fosfomycin-resistant clinical strains were either virulent (2/7) or non-virulent (5/7) (P<0.002). This difference was not explained by the number of virulence factors or pathogenicity-associated islands. In conclusion, fosfomycin resistance appears to carry some biological cost in E. coli, which may explain in part the apparent paradox of the low prevalence of fosfomycin resistance despite a high rate of spontaneous mutants.

Clinical and microbiological features associated with group B Streptococcus bone and joint infections, France 2004-2014.

This study describes the clinical and microbiological features associated with group B Streptococcus (GBS) bone and joint infections (BJIs). It was a retrospective analysis of adult cases of GBS BJIs reported to the French National Reference Center for Streptococci from January 2004 to December 2014. Clinical data and GBS molecular characteristics are reported. Strains were collected from 163 patients. The most frequent comorbidities were: solid organ cancer (n = 21, 21%) and diabetes mellitus (n = 20, 20%). The main infection sites were knee (47/155 = 30%) and hip (43/155 = 27%), and occurred on orthopedic devices in 71/148 cases (48%). CPS III (n = 47, 29%), Ia (n = 26, 16%) and V (n = 40, 25%) were predominant. Resistance to erythromycin, clindamycin and tetracycline was detected in 55/163 (34%), 35/163 (21%) and 132/163 (81%) strains, respectively. The most frequent sequence types were ST-1 (n = 21, 25%), ST-17 (n = 17, 20%) and ST-23 (n = 11, 13%). The rate of resistance to erythromycin was 0% for ST-17 strains, 52% (n = 11) for ST-1 and 44% (n = 7) for ST-23 (p < 0.001). GBS bone and joint infections predominantly occur in patients aged >50 years and/or with comorbidities such as cancer and diabetes mellitus. CPS type distribution and MLST are very similar to that of other adult GBS invasive infections.

Bacterial epidemiology and antimicrobial resistance profiles of urinary specimens of the elderly.

OBJECTIVE: Although urinary tract infections are the second leading cause of infections among patients aged above 65 years, data on bacterial epidemiology of urinary specimens in these patients is scarce. Our aim was to describe the main bacterial species found at significant levels in urine specimens of the elderly and to determine their antimicrobial resistance profiles. METHODS: From October 2012 to October 2015, all urinary specimens (catheter-related or not) received at the laboratory of microbiology of the university hospital of Caen (France) were retrospectively studied. Results were compared to those of urinary specimens of patients aged 18-64 years. Bacterial identification was performed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing was performed as per CA-SFM guidelines. RESULTS: Out of 33,302 urine cytobacteriological examinations (UCBE) performed in patients aged above 65 years, 13,450 microorganisms were identified. Escherichia coli was the most frequent species (41.8%) followed by Enterococcus faecalis (9.7%), Pseudomonas aeruginosa (5.7%), Proteus mirabilis (4.6%), and Klebsiella pneumoniae (4.2%). Around 9% of E. coli isolates were resistant to third-generation cephalosporins, including 8.2% by production of extended-spectrum ß-lactamase (ESBL). This prevalence was significantly higher than that observed in urinary specimens of patients aged 18-74 years (4.9%, P<0.001). CONCLUSION: The bacterial epidemiology of urines collected from the elderly is diverse and significantly different from that of urine specimens of younger patients, with a higher proportion of multidrug-resistant bacteria (particularly ESBL-producing E. coli).

Inventory of Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study.

The objective of this study was to perform an inventory of the extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr, and aac(3)-II genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the Enterobacteriaceae species.

Outcome of patients with streptococcal prosthetic joint infections with special reference to rifampicin combinations.

BACKGROUND: Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known. METHODS: We performed a retrospective multicenter cohort study that involved patients with total hip/knee prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009. RESULTS: Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04). CONCLUSIONS: The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients.

First nosocomial outbreak of vanA-type vancomycin-resistant Enterococcus raffinosus in France.

BACKGROUND: Vancomycin-resistant Enterococcus raffinosus has rarely been associated with nosocomial infection and outbreaks. AIM: To report the successful control of a nosocomial outbreak of vanA-type vancomycin-resistant E. raffinosus in a surgical intensive care unit. METHODS: The investigation of the outbreak is reported with control measures taken. Molecular typing of vancomycin-resistant E. raffinosus isolates was performed by repetitive sequence-based polymerase chain reaction (PCR). FINDINGS: Between September and October 2014, vancomycin-resistant E. raffinosus isolates were isolated from four patients. The index patient had been hospitalized previously in Portugal, and was not found to be colonized by vancomycin-resistant enterococci on screening cultures obtained at admission. However, vancomycin-resistant E. raffinosus was isolated from a bile sample 19 days after hospital admission. All four isolates were resistant to both vancomycin and teicoplanin due to the presence of the vanA gene, while remaining susceptible to daptomycin and linezolid. Repetitive sequence-based PCR confirmed the spread of a single vanA-positive E. raffinosus clone. Infection control measures including direct PCR screening on rectal specimens, contact precautions, and cohorting of patients and personnel led to successful control of the outbreak. CONCLUSION: This is the first reported outbreak of vanA-type vancomycin-resistant E. raffinosus in France in both clinical and screening specimens among hospitalized patients. The inability of routine selective screening media to detect the vancomycin-resistant E. raffinosus in the index case likely contributed to the outbreak.

Hajj-associated infections.

BACKGROUND: The Hajj is the largest annual mass gathering event in the world, thus favoring the transmission of various infections: 183 different nationalities, high temperatures, coincidence with the start of the flu season in the Northern hemisphere, a long barefoot walk, tent-type accommodation, communal toilet facilities, absence of food control, and sharing of razors. Infections are the first cause of hospital admission, which often occurs in the home country of pilgrims. METHODS: Literature review on PubMed from 1952 to November 2015 on the epidemiology and prevention of infections contracted during the Hajj, using the keywords "Hajj" and "infections". RESULTS: Respiratory tract infections, ENT infections, influenza, pyogenic pneumonia, whooping cough, and tuberculosis are most frequently observed during the Hajj. Outbreaks of meningococcal meningitis have been reported in pilgrims and their contacts. Waterborne infections such as gastroenteritis and hepatitis A are common, despite the improvement of health conditions. Pyoderma and furuncles are also frequently observed. Recently, dengue fever, Alkhumra hemorrhagic fever, and Rift Valley fever have emerged but no case of MERS-coronavirus, appeared in Saudi Arabia in 2012, have yet been observed during the 2012-2014 Hajj. CONCLUSION: Prevention is based on compulsory meningococcal vaccination, vaccination against seasonal influenza and pneumococcal infections for pilgrims at high risk of contracting the infection, and on vaccination against hepatitis A. Updating immunization for diphtheria/tetanus/poliomyelitis/pertussis and measles/mumps is also crucial and pilgrims must comply with hygiene precautions.

Activity of temocillin in a lethal murine model of infection of intra-abdominal origin due to KPC-producing Escherichia coli.

OBJECTIVES: Temocillin is a 6-α-methoxy derivative of ticarcillin that shows in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC). Our objective was to assess in vivo temocillin activity against KPC-producing Escherichia coli. METHODS: Isogenic derivatives of the WT E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental murine model of intra-abdominal infection with sepsis was used. Mice were treated subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the duration of time that the free serum concentration of temocillin exceeded the MIC in humans with a regimen of 2 g every 12 h or 2 g every 8 h. Blood, peritoneal fluid (PF) and spleen were collected; 24 h survival and sterility rates were assessed. RESULTS: Temocillin MICs were 8, 16, 32, and 256 mg/L for the susceptible strain and KPC-2-, KPC-3-, and OXA-48-producing strains, respectively. In mice treated with temocillin, significant bacterial reduction was obtained in PF, blood, and spleen for the susceptible strain and KPC-2- and KPC-3-producing strains (P < 0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%, 57%, 0% (P < 0.001) for mice infected with the susceptible strain and KPC-2-, KPC-3- and OXA-48-producing strains, respectively. CONCLUSIONS: In a lethal-infection model with bacteraemia from intra-abdominal origin, temocillin retained significant activity in PF, blood and spleen and prevented death in mice by effectively working against KPC-producing E. coli with temocillin MICs ≤16 mg/L.