Cefotaxime and Amoxicillin-Clavulanate Synergism against Extended-Spectrum-ß-Lactamase-Producing Escherichia coli in a Murine Model of Urinary Tract Infection.

We investigated the efficacies of cefotaxime (CTX) and amoxicillin (AMX)-clavulanate (CLA) (AMC) against extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli in vitro and in a murine model of urinary tract infection (UTI). MICs, the checkerboard dilution method, and time-kill curves were used to explore the in vitro synergism between cefotaxime and amoxicillin-clavulanate against two isogenic E. coli strains-CFT073-RR and its transconjugant, CFT073-RR Tc bla(CTX-M-15)-harboring a bla(CTX-M-15) plasmid and a bla(OXA-1) plasmid. For in vivo experiments, mice were separately infected with each strain and treated with cefotaxime, amoxicillin, and clavulanate, alone or in combination, or imipenem, using therapeutic regimens reproducing time of free-drug concentrations above the MIC (fT≥MIC) values close to that obtained in humans. MICs of amoxicillin, cefotaxime, and imipenem were 4/>1,024, 0.125/1,024, and 0.5/0.5 mg/liter, for CFT073-RR and CFT073-RR Tc bla(CTX-M-15), respectively. The addition of 2 mg/liter of clavulanate (CLA) restored the susceptibility of CFT073-RR Tc bla(CTX-M-15) to CTX (MICs of the CTX-CLA combination, 0.125 mg/liter). The checkerboard dilution method and time-kill curves confirmed an in vitro synergy between amoxicillin-clavulanate and cefotaxime against CFT073-RR Tc bla(CTX-M-15). In vivo, this antibiotic combination was similarly active against both strains and as effective as imipenem. In conclusion, the cefotaxime and amoxicillin-clavulanate combination appear to be an effective, easy, and already available alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli strains.

Activity of temocillin in a murine model of urinary tract infection due to Escherichia coli producing or not producing the ESBL CTX-M-15.

OBJECTIVES: Temocillin is a 6α-methoxy derivative of ticarcillin that is resilient to ESBLs. Prospective data about its in vivo activity remain scarce. Our aims were: (i) to evaluate the activity of temocillin in a urinary tract infection (UTI) model due to ESBL-producing Escherichia coli and compare it with that of imipenem; and (ii) to define in vivo susceptibility breakpoints. METHODS: Mice were infected with a susceptible E. coli CFT073-RR or its transconjugant (CFT073-RR Tc) harbouring a blaCTX-M-15-carrying plasmid, using an ascending UTI model. Therapeutic regimens were chosen in order to reproduce percentage of time of free drug concentrations above MIC (fT>MIC) obtained in humans with standard regimens of temocillin (200 mg/kg every 2 h for 2 g every 12 h) or imipenem (100 mg/kg every 2 h for 1 g every 8 h). Additional regimens of temocillin (200 mg/kg every 4 and 6 h) with reduced fT>MIC were studied. RESULTS: MICs of temocillin and imipenem were 4/8 and 0.5/0.5 mg/L, for CFT073-RR and CFT073-RR Tc, respectively. In vivo, when given every 2 h (fT>MIC = 82% and 70%), temocillin was bactericidal and as effective as imipenem in kidneys against both strains without selecting resistant mutants. Temocillin remained active even when given every 4 h, generating an fT>MIC of 41% and 35%, which corresponded to a breakpoint of 16 mg/L in humans with the standard regimen. CONCLUSIONS: Our observations support the consideration of a standard regimen of temocillin as an alternative to carbapenems for the treatment of UTI due to CTX-M-producing E. coli strains with an MIC of 16 mg/L or less.

[Acute respiratory distress syndrome complicating an acute chest syndrome: potential benefit of early combination of exchange transfusion and prone positioning]. / Syndrome de défaillance respiratoire aiguë sévère au cours d'un syndrome thoracique aigu chez une enfant drépanocytaire de 8ans : bénéfice potentiel de l'association précoce échange transfusionnel et décubitus ventral.

We report the case of an 8-year-old sickle cell anemia child admitted for acute respiratory failure complicating acute chest syndrome. Because of threatening respiratory failure, tracheal intubation was performed immediately after ICU admission. The patient met the criteria for ARDS with a PaO2/FiO2 ratio of 94mmHg. An exchange transfusion was performed immediately after admission. HbS fraction failed from 69 % to 30 %. Fluid resuscitation with crystalloids and continuous norepinephrine infusion was needed because of arterial hypotension. Due to persistent severe hypoxemia with PaO2/FiO2 ratio below 100, the patient was placed in prone positioning 16hours after admission, for a total duration of 14hours. A second 12-hour session of prone positioning was performed 41h after admission and PaO2/FiO2 ratio reached 300mmHg after. Treatment also included transfusion of two red-cell pack on day 1 and 2 after admission in order to maintain hemoglobin level above 8g/dL, and a daily folic acid supplementation. The control of hyperthermia was achieved by a systematic parenteral administration of paracetamol. Cefotaxime and erythromycine were continued until day 7 despite the negative results of all bacteriological samples. The outcome was favorable from day 3 and the patient met the criteria for extubation on day 5. A first attempt of extubation was performed on day 5, but re-intubation was required because of laryngeal edema. Steroids were given for 48h and the patient was successfully extubated on day 7. She was discharged from the ICU on day 8, and from the hospital on day 12. We discuss the various treatments available for the management of acute chest syndrome and their actual relevance in acute respiratory distress syndrome in the absence of strong evidence-based guidelines in pediatric ARDS.

An individual scoring system for the prediction of postpartum anaemia.

BACKGROUND: Postpartum anaemia (PPA) is a common postpartum complication. The goal of this study was to prospectively construct a predictive score for individual risk of PPA. PATIENTS ET METHOD: We prospectively analyzed factors associated with PPA (<10gdL(-1) at 48hours postpartum). Parameters analyzed were demographic data, pregnancy characteristics, delivery and postpartum characteristics. Univariate analysis was performed using Anova or X(2); the Cox model was used for multivariate analysis. The scoring system was validated using ROC curve. RESULTS: Analysis was performed in 475 patients and validation was carried using an additional 95 patients. Multivariate analysis found four factors independently associated with PPA: anaemia during the third trimester of the pregnancy, Southeast Asian ethnic origin, episiotomy and severe postpartum haemorrhage (PPH) identified by the use of sulprostone. According to the score derived from the Cox model, patients were classified as low (22%, score=0), medium (55%, score=2 or 3) and high (86%, score>3) probability of PPA. Using the AUC of the ROC curve for both the first and the validation cohorts (performed on 95 further patients), we recorded AUCs of 72% and 70% respectively. CONCLUSIONS: This study allowed the derivation and validation of a predictive score of PPA. This score might be useful in targeting prophylactic strategies for PPA. Such strategies could include a more active treatment of iron deficiency (increasing oral iron treatment observance or intravenous iron therapy) especially in exposed population, improvement in the prevention and treatment of postpartum haemorrhage and decreasing the use of episiotomy. Future studies must focus on the external validation and generalisation of this scoring system.