Toward an optimization of empirical antibiotic therapy in acute graft pyelonephritis: A retrospective multicenter study.

OBJECTIVE: Acute graft pyelonephritis (AGPN) is the most frequent infectious complication in kidney transplant recipients (KTR). The treatment of acute community-acquired (CA) pyelonephritis is based on third-generation cephalosporins (3GC) and fluoroquinolones. Cefepime or a piperacillin-tazobactam combination are more often used in healthcare-associated (HCA) infections. However, these recommendations do not consider the resistance observed in KTRs. The objective of our study was to define the most appropriate empirical antibiotherapy for AGPN in KTRs according to the CA and HCA settings. To answer this question, we assessed the prevalence of resistance to different antibiotics usually recommended for urinary tract infections (UTIs) in the general population. METHODS: Observational, retrospective, multicenter study covering all episodes of AGPN occurring in hospitalized KTRs in 2019. RESULTS: A total of 210 patients were included in 7 centers and 244 episodes of AGPN were analyzed (158 CA-AGPN and 86 HCA-AGPN). The prevalence of 3GC and fluoroquinolone resistance was 23 % (n = 36) and 30 % (n = 50) in CA infections (n = 158), and 47 % (n = 40) and 31 % (n = 27) in HCA infections (n = 86), respectively. Cefepime resistance rate was 19 % (n = 30) in CA-AGPN and 29 % (n = 25) in HCA-AGPN. Piperacillin-tazobactam combination had resistance rates > 15 % in both CA and HCA infections. The only antimicrobials with resistance rates < 10 % were aminoglycosides and carbapenems. CONCLUSION: None of the antibiotics recommended in empirical treatment in UTIs has shown a resistance rate of less than 10% with regard to AGPN. Therefore, none of them should be used as monotherapy. A combination therapy including amikacin could be an appropriate strategy in this setting.

Impact of Enterococcus faecalis Endocarditis Treatment on Risk of Relapse.

BACKGROUND: Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. MATERIALS: This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. RESULTS: Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death.The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis). CONCLUSIONS: Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.

A Retrospective Study on Amoxicillin Susceptibility in Severe Haemophilus influenzae Pneumonia.

INTRODUCTION: Treatment of Haemophilus influenzae (Hi) pneumonia is on concern because resistance to amoxicillin is largely diffused. This study describes the evolution of resistance to amoxicillin and amoxicillin/clavulanic acid (AMC) in Hi isolates and characteristics of patients with Hi severe pneumonia. METHODS: A monocentric retrospective observational study including patients from 2008 to 2017 with severe pneumonia hospitalized in ICU. Evolution of amoxicillin and AMC susceptibility was showed. Characteristics of patients with Hi pneumonia were compared to characteristics of patients with Streptococcus pneumoniae (Sp) pneumonia, as reference. Risk factors for amoxicillin resistance in Hi were investigated. RESULTS: Overall, 113 patients with Hi and 132 with Sp pneumonia were included. The percentages of AMC resistance among Hi strains decreased over the years (from 10% in 2008-2009 to 0% in 2016-2017) while resistance to amoxicillin remained stable at 20%. Also, percentages of Sp resistant strains for amoxicillin decreased over years (from 25% to 3%). Patients with Hi pneumonia experienced higher prevalence of bronchitis (18% vs. 8%, p=0.02, chronic obstructive pulmonary disease (43% vs. 30% p=0.03), HAP (18% vs. 7%, p=0.01, ventilator-associated pneumonia (27% vs. 17%, p=0.04, and longer duration of mechanical ventilation (8 days vs. 6 days, p=0.04) than patients with Sp pneumonia. Patients with Sp pneumonia had more frequently local complications than patients with Hi pneumonia (17% vs. 7%, p=0.03). De-escalation of antibiotics was more frequent in patients with Sp than in patients with Hi (67% vs. 53%, p=0.03). No risk factors were associated with amoxicillin resistance among patients with Hi pneumonia. CONCLUSIONS: Amoxicillin resistance was stable over time, but no risk factors were detected. AMC resistance was extremely low, suggesting that AMC could be used for empiric treatment of Hi pneumonia, as well as other molecules, namely, cephalosporins. Patients with Hi pneumonia had more pulmonary comorbidities and severe diseases than patients with Sp pneumonia.

Evolution of haemostatic parameters and risk of bleeding during treatment with cefazolin.

In 2017, five cases of severe haemorrhages during treatment with cefazolin occurred in France. The aim of this study was to assess the risk of haemorrhage related to treatment with cefazolin by evaluating haemostatic parameters and bleeding events. A retrospective study was conducted from January 2016 to December 2017. Two populations were analysed: (i) overall population, which included all patients treated with cefazolin during this period and (ii) coagulation study population, which included all patients treated with cefazolin with available coagulation parameters (activated partial thromboplastin time (aPTT) and international normalised ratio (INR) at baseline and at the end of treatment or EoT). Values of either aPTT or INR at baseline and at EoT were compared. Cases of severe haemorrhages were reported and correlated with values of aPTT and INR. Overall, 132 patients received cefazolin and 59/132 (45%) were included in the coagulation study group. A significant increase of median aPTT was observed from baseline to EoT (39.5 and 44.3 sec; p = 0.004, respectively). Overall, severe haemorrhage occurred in 7/132 (5%) patients. Coagulation parameters were available in three of them, and no correlation was observed between bleeding events and aPTT increase. This study showed that bleeding is probably more frequent than ever reported before during cefazolin treatment. The significant increase of aPTT observed during cefazolin treatment was not correlated with risk of haemorrhage. Further studies are needed to explore the possible physio-pathological pathways behind the modification of haemostatic parameters and risk of haemorrhage.