Defining standard and high dosages for ß-lactam agents administered by intermittent, prolonged or continuous infusion: a PK/PD simulation study.

BACKGROUND: The new definitions of antimicrobial susceptibility categories proposed by EUCAST in 2020 require the definition of standard and high dosages of antibiotic. For injectable ß-lactams, standard and high dosages have been proposed for short-infusion regimens only. OBJECTIVES: To evaluate dosages for ß-lactams administered by prolonged infusion (PI) and continuous infusion (CI). METHODS: Monte Carlo simulations were performed for seven injectable ß-lactams: aztreonam, cefepime, cefotaxime, cefoxitin, ceftazidime, piperacillin and temocillin. Various dosage regimens based on short infusion, PI or CI were simulated in virtual patients. Pharmacokinetic (PK) profiles and PTAs were obtained based on reference population PK models, as well as PK/pharmacodynamic targets and MIC breakpoints proposed by EUCAST. Alternative dosage regimens associated with PTA values similar to those of recommended dosages up to the breakpoints were considered acceptable. RESULTS: Adequate PTAs were confirmed for most EUCAST short-infusion dosage regimens. A total of 9 standard and 14 high dosages based on PI (3 to 4 h) or CI were identified as alternatives. For cefepime and aztreonam, only PI and CI regimens could achieve acceptable PTAs for infections caused by Pseudomonas spp.: 2 g q8h as PI of 4 h or 6 g/24 h CI for cefepime; 2 g q6h as PI of 3 h or 6 g/24 h CI for aztreonam. CONCLUSIONS: These alternative standard and high dosage regimens are expected to provide antibiotic exposure compatible with new EUCAST definitions of susceptibility categories and associated MIC breakpoints. However, further clinical evaluation is necessary.

Oral levofloxacin: population pharmacokinetics model and pharmacodynamics study in bone and joint infections.

OBJECTIVES: This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). METHODS: From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). RESULTS: One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). CONCLUSIONS: Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Comparing Dynamics and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 Transmissions Among Healthcare Workers of Adult and Pediatric Settings in Central Paris.

BACKGROUND: Healthcare workers (HCWs) have paid a heavy toll during the coronavirus disease 2019 (COVID-19) outbreak. Routes of transmission remain to be fully understood. METHODS: This prospective study compared a 1500-bed adult and 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. From 24 February until 10 April 2020, all symptomatic HCWs were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a nasopharyngeal swab. HCWs screened positive were questioned on their profession, symptoms, and occupational and nonoccupational exposures to SARS-CoV-2. RESULTS: Among 1344 HCWs tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no deaths were reported. Most HCWs (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on 23 March, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment [PPE] for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric settings, respectively (P = .0022). In the adult setting, HCWs more frequently reported exposure to COVID-19 patients without PPE (25% vs 15%, P = .046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period. CONCLUSIONS: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCWs and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.

Are infection specialists recommending short antibiotic treatment durations? An ESCMID international cross-sectional survey.

Objectives: To evaluate the current practice and the willingness to shorten the duration of antibiotic therapy among infection specialists. Methods: Infection specialists giving at least weekly advice on antibiotic prescriptions were invited to participate in an online cross-sectional survey between September and December 2016. The questionnaire included 15 clinical vignettes corresponding to common clinical cases with favourable outcomes; part A asked about the antibiotic treatment duration they would usually advise to prescribers and part B asked about the shortest duration they were willing to recommend. Results: We included 866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty-six percent of participants (271/749) already advised short durations of antibiotic therapy (compared with the literature) to prescribers for more than half of the vignettes and 47% (312/662) chose shorter durations in part B compared with part A for more than half of the vignettes. Twenty-two percent (192/861) of the participants declared that their regional/national guidelines expressed durations of antibiotic therapy for a specific clinical situation as a fixed duration as opposed to a range and in the multivariable analysis this was associated with respondents advising short durations for more than half of the vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection specialists currently do not advise the shortest possible duration of antibiotic therapy to prescribers. Promoting short durations among these experts is urgently needed.

Efficacy and quality of antibacterial generic products approved for human use: a systematic review.

BACKGROUND: Concerns have recently emerged about the efficacy and the quality of antibacterial generic products approved for use in humans. METHODS: We searched Medline and Embase for original research articles on antibacterial generic products published in English or French before July 2013. RESULTS: We selected 37 original research articles: 15 on ß-lactams, 10 on glycopeptides, and 12 on other antibacterial agents. The majority of articles (73.0%) were published during 2008-2012. Study designs included analytical chemistry (n = 9), in vitro susceptibility studies (n = 14), animal experiments (n = 6, including 5 using the neutropenic mouse thigh infection model), and clinical studies in humans (n = 15). Of the 37 studies, 14 (37.8%) suggested that some generic products may be inferior to the innovator in terms of purity (n = 2), in vitro activity (n = 3), in vivo efficacy in experimental models (n = 4), clinical efficacy (n = 2), taste (n = 2), or compliance and acceptability in children (n = 1). The majority of in vitro studies (78.6%) found no significant difference between generic products and the innovator. Most (5/6) in vivo studies suggesting a difference between generic products and the innovator were performed in an animal model that is not validated for the evaluation of the efficacy of antibacterial agents. The level of evidence was constantly low in clinical studies. CONCLUSIONS: Published data on antibacterial generic products are limited and heterogeneous, thus precluding any attempt to generalize the study results. This systematic review suggests that additional evidence would be needed before considering a revision of the marketing authorization process for antibacterial generic products.

Jugular versus femoral short-term catheterization and risk of infection in intensive care unit patients. Causal analysis of two randomized trials.

RATIONALE: When subclavian access is not possible, controversy exists between the internal jugular and femoral sites for the choice of central-venous access in intensive care unit patients. OBJECTIVES: To compare infection and colonization rates of short-term jugular and femoral catheters. METHODS: Using data from two multicenter studies, we compared femoral and internal jugular for the risks of catheter-related bloodstream infection, major catheter-related infection, and catheter-tip colonization. We also compared the rates of dressing disruption and skin colonization. We used marginal structural models with inverse probability of treatment weighting to adjust on indication bias. MEASUREMENTS AND MAIN RESULTS: We included 2,128 patients (2,527 catheters and 19,481 catheter-days). We found no difference in catheter-related bloodstream infection (internal jugular 1.0 vs. femoral 1.1 per 1,000 catheter-days; hazard ratio [HR], 0.63 [0.25-1.63]; P = 0.34), major catheter-related infection (internal jugular 1.8 vs. femoral 1.4 per 1,000 catheter-days; HR, 0.91 [0.38-2.18]; P = 0.34), and colonization (internal jugular 11.6 vs. femoral 12.9 per 1,000 catheter-days; HR, 0.80 [0.25-1.63]; P = 0.15). However, colonization was higher with femoral for female (HR, 0.39 [0.24-0.63]; P < 0.001) and, at the significance limit, catheter maintained for more than 4 days (HR, 0.73 [0.53-1.01]; P = 0.05). The absence of benefit of internal jugular before Day 5 was related to a higher skin colonization at the internal jugular site for catheters removed before Day 5. After the fourth day, dressing disruption became more frequent with femoral catheters and may explain the subsequent risk of catheter colonization. Differences in cutaneous and catheter colonization between internal jugular and femoral was suppressed by the use of chlorhexidine-impregnated dressings. CONCLUSIONS: Femoral and internal jugular accesses lead to similar risks of catheter infection. Internal jugular might be preferred for female, nonchlorhexidine-impregnated dressings users, and when catheters are left in place more than 4 days. Both sites are acceptable when a subclavian approach is not feasible. Clinical trial registered with www.clinicaltrials.gov (NCT00417235 and NCT01189682).

Randomized controlled trial of chlorhexidine dressing and highly adhesive dressing for preventing catheter-related infections in critically ill adults.

RATIONALE: Most vascular catheter-related infections (CRIs) occur extraluminally in patients in the intensive care unit (ICU). Chlorhexidine-impregnated and strongly adherent dressings may decrease catheter colonization and CRI rates. OBJECTIVES: To determine if chlorhexidine-impregnated and strongly adherent dressings decrease catheter colonization and CRI rates. METHODS: In a 2:1:1 assessor-masked randomized trial in patients with vascular catheters inserted for an expected duration of 48 hours or more in 12 French ICUs, we compared chlorhexidine dressings, highly adhesive dressings, and standard dressings from May 2010 to July 2011. Coprimary endpoints were major CRI with or without catheter-related bloodstream infection (CR-BSI) with chlorhexidine versus nonchlorhexidine dressings and catheter colonization rate with highly adhesive nonchlorhexidine versus standard nonchlorhexidine dressings. Catheter-colonization, CR-BSIs, and skin reactions were secondary endpoints. MEASUREMENTS AND MAIN RESULTS: A total of 1,879 patients (4,163 catheters and 34,339 catheter-days) were evaluated. With chlorhexidine dressings, the major-CRI rate was 67% lower (0.7 per 1,000 vs. 2.1 per 1,000 catheter-days; hazard ratio [HR], 0.328; 95% confidence interval [CI], 0.174-0.619; P = 0.0006) and the CR-BSI rate 60% lower (0.5 per 1,000 vs. 1.3 per 1,000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868; P = 0.02) than with nonchlorhexidine dressings; decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% versus 71.9% (P < 0.0001) and the number of dressings per catheter to two (one to four) versus three (one to five) (P < 0.0001) but increased skin colonization (P < 0.0001) and catheter colonization (HR, 1.650; 95% CI, 1.21-2.26; P = 0.0016) without influencing CRI or CR-BSI rates. CONCLUSIONS: A large randomized trial demonstrated that chlorhexidine-gel-impregnated dressings decreased the CRI rate in patients in the ICU with intravascular catheters. Highly adhesive dressings decreased dressing detachment but increased skin and catheter colonization. Clinical trial registered with www.clinicaltrials.gov (NCT 01189682).

Safety of high loading doses of teicoplanin: POSY-TEICO, a prospective, multicentre, observational study.

BACKGROUND: Teicoplanin is used for treating infections caused by Gram-positive bacteria. The POSY-TEICO study assessed the safety of a high loading dose (HLD) of teicoplanin (12 mg/kg twice daily) in a real-world setting. METHODS: This prospective study was conducted across six countries in Europe and enrolled adults prescribed HLD of teicoplanin between 2016 and 2019. The primary objective was to determine the incidence of nephrotoxicity following HLD of teicoplanin over loading dose period. An independent clinical adjudication committee (ICAC) assessed all study outcomes related to nephrotoxicity. RESULTS: The study included 300 patients (males, 68.3%), with a mean age of 63.1 years and median teicoplanin treatment duration of 16 days (interquartile range: 9-38). The number of patients with bone and joint infection, infective endocarditis, and other severe infections was 176, 36, and 80, respectively. During the loading dose period, 41 (13.8%) patients received 3 HLDs and 246 (82.8%) received ≥4 HLDs. Overall, 28 (11.0%) patients (95% CI, 7.4-15.5) experienced nephrotoxicity during loading, and 10 (6.9%) patients (95% CI, 3.4-12.4) during maintenance dose periods. The number of patients who experienced nephrotoxicity certainly or possibly related to teicoplanin according to the ICAC was 20 (7.9%; 95% CI, 4.9-11.9), 8 (5.6%; 95% CI, 2.4-10.7) and 33 (12.4%; 95% CI, 8.7-16.9) across three study periods. CONCLUSIONS: HLD of teicoplanin had an acceptable safety profile in patients treated for bone and joint infection, infective endocarditis, and other severe infections, and no increased risk of nephrotoxicity was observed. However, patients should be closely monitored when HLDs are administered.

Extended antibiotic prophylaxis after pancreatoduodenectomy reduces postoperative abdominal infection in high-risk patients: Results from a retrospective cohort study.

BACKGROUND: Preoperative biliary stenting before pancreatoduodenectomy is associated with a greater risk of bacteribilia and thus could lead to more frequent and severe surgical site infections. We hypothesized that an extended antibiotic prophylaxis could reduce the risk of surgical site infections for these high-risk patients compared with standard antibiotic prophylaxis. METHODS: All consecutive patients who underwent pancreatoduodenectomy between January 1, 2010 and December 31, 2016 were included in a tricentric retrospective cohort and classified according to the risk of surgical site infections (high or low) and the type of antibiotic prophylaxis (standard or extended). Extended antibiotic prophylaxis was defined by the use of high-rank ß-lactams >2 days after surgery. Standard antibiotic prophylaxis concerned all single dose of low-rank ß-lactams antibiotic prophylaxis. The primary outcome was postoperative surgical site infections. RESULTS: Three hundred and eight patients were included; 146 (47%) were high-risk patients, and 81 (55%) received extended antibiotic prophylaxis, mostly composed of piperacilline-tazobactam and gentamicin. There were significantly fewer surgical site infections in high-risk patients receiving extended antibiotic prophylaxis versus standard antibiotic prophylaxis (odds ratio = 0.4; 95% confidence interval, 0.2-0.8; P = .011), even after adjusting on age, sex, and duration of the surgical procedure (adjusted odds ratio = 0.3; 95% confidence interval, 0.1-0.7; P = .0071). There was no statistical difference in 28-day mortality (P = .32) or 90-day mortality (P = .13). Microorganisms identified in bile culture were more often sensitive to antibiotic prophylaxis in high-risk extended antibiotic prophylaxis group than in high-risk standard antibiotic prophylaxis group (64% versus 38%; P = .01). CONCLUSION: Extended antibiotic prophylaxis is associated with a reduced risk of surgical site infections for high-risk patients with no significant reduction on 28-day mortality. Additional studies are required to determine the optimal duration of extended antibiotic prophylaxis for these patients.

Dual beta-lactam treatment: Pros and cons.

The battle against microscopic pathogens has always baffled the scientific community. Nowadays, multidrug-resistant microorganisms lead to high in-hospital mortality, increased hospital stays, and high health-related costs. Treating infections due to these high-resistance pathogens with a low number of antibiotic molecules creates the need for new strategies. Although some already think of a "postantibiotic era" with bacteriophages as the main futuristic weapon in antibacterial armament, others rethink the usage of the already existent drugs. Dual beta-lactam therapy has been used for quite some time as an empirical therapy for some severe infections such as endocarditis or meningitis. However, studies regarding the use of a beta-lactam combination stopped being made a long time ago, and it seems the scientific community has no interest in evaluating this as a treatment option. Could this strategy be applied to treat infections due to multidrug-resistant bacteria? Could this be the answer while waiting for the "postantibiotic era"? What kind of pathogens could we fight using dual beta-lactams? What are the downsides of this strategy? These are some of the questions the authors try to answer in this review. In addition, we try to convince our peers to turn once more into researching beta-lactam combinations and exploring its potential benefits.

Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units.

INTRODUCTION: Few studies have addressed the decision-making process of antibiotic therapy (AT) in intensive care unit (ICU) patients. METHODS: In a prospective observational study, all consecutive patients admitted over a one-month period (2004) to 41 French surgical (n = 22) or medical/medico-surgical ICUs (n = 19) in 29 teaching university and 12 non-teaching hospitals were screened daily for AT until ICU discharge. We assessed the modalities of initiating AT, reasons for changes and factors associated with in ICU mortality including a specific analysis of a new AT administered on suspicion of a new infection. RESULTS: A total of 1,043 patients (61% of the cohort) received antibiotics during their ICU stay. Thirty percent (509) of them received new AT mostly for suspected diagnosis of pneumonia (47%), bacteremia (24%), or intra-abdominal (21%) infections. New AT was prescribed on day shifts (45%) and out-of-hours (55%), mainly by a single senior physician (78%) or by a team decision (17%). This new AT was mainly started at the time of suspicion of infection (71%) and on the results of Gram-stained direct examination (21%). Susceptibility testing was performed in 261 (51%) patients with a new AT. This new AT was judged inappropriate in 58 of these 261 (22%) patients. In ICUs with written protocols for empiric AT (n = 25), new AT prescribed before the availability of culture results (P = 0.003) and out-of-hours (P = 0.04) was more frequently observed than in ICUs without protocols but the appropriateness of AT was not different. In multivariate analysis, the predictive factors of mortality for patients with new AT were absence of protocols for empiric AT (adjusted odds ratio (OR) = 1.64, 95% confidence interval (95%CI): 1.01 to 2.69), age ≥60 (OR = 1.97, 95% CI: 1.19 to 3.26), SAPS II score >38 (OR = 2.78, 95% CI: 1.60 to 4.84), rapidly fatal underlying diseases (OR = 2.91, 95% CI: 1.52 to 5.56), SOFA score ≥6 (OR = 4.48, 95% CI: 2.46 to 8.18). CONCLUSIONS: More than 60% of patients received AT during their ICU stay. Half of them received new AT, frequently initiated out-of-hours. In ICUs with written protocols, empiric AT was initiated more rapidly at the time of suspicion of infection and out-of-hours. These results encourage the establishment of local recommendations for empiric AT.

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

OBJECTIVE: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Early prediction of Candida glabrata fungemia in nonneutropenic critically ill patients.

OBJECTIVE: Candida species represent the fourth cause of nosocomial bloodstream infections worldwide. Because Candida glabrata has become the second most frequently identified yeast and because the rate of fluconazole-resistant C. glabrata strains reaches 10% to 15%, initial antifungal therapy based on fluconazole in nonneutropenic hemodynamically stable patients, as recommended by current guidelines, may be an ineffective option. Our aim was to determine easy-to-identify risk factors for C. glabrata fungemia likely to guide and improve initial antifungal therapy. DESIGN: Prospective multicenter cohort study. SETTING: Five French intensive care units. PATIENTS: Consecutive nonneutropenic patients without known Candida colonization who had blood culture-confirmed fungemia over a 4-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 8206 patients were screened. One hundred fifty-four patients with blood culture-confirmed fungemia constituted the cohort, of whom 48 had C. glabrata fungemia and 106 had nonglabrata fungemia. Patients' baseline characteristics and in-intensive care unit events potentially related to C. glabrata fungemia were systematically recorded. Compared with patients with nonglabrata fungemia, patients with C. glabrata fungemia were older and more severely ill, had received more antibiotics, and were more likely to have undergone surgery. The stepwise logistic regression analysis identified six independent risk factors for C. glabrata fungemia: age >60 yrs, recent abdominal surgery, interval from intensive care unit admission to first positive blood culture

Impact of an Antimicrobial Stewardship Program on Resistance to Fluoroquinolones of Urinary Enterobacteriaceae Isolated From Nursing Home Residents: A Retrospective Cohort Study.

OBJECTIVES: This study investigated the impact of an antimicrobial stewardship program on fluoroquinolone (FLQ) resistance in urinary Enterobacteriaceae isolated from residents of 3 French nursing homes. DESIGN: A multicentric retrospective before-and-after study was conducted. SETTING AND PARTICIPANTS: All the first urinary Enterobacteriaceae isolates obtained from nursing home residents were included. Two time frames were analyzed: 2013-2015 and 2016-2017. METHODS: The antimicrobial stewardship program started in 2015 and was based on (1) 1-day training for use of an "antimicrobial stewardship kit for nursing homes;" and (2) daily support and training of the coordinating physician by an antibiotic mobile team (AMT) in 2 of 3 nursing homes. RESULTS: Overall, 338 urinary isolates were analyzed. Escherichia coli was the most frequent species (212/338, 63%). A significant reduction of resistance to ofloxacin was observed between 2013-2015 and 2016-2017 in general (Δ = -16%, P = .004) and among isolates obtained from patients hospitalized in the county nursing home with AMT support (Δ = -28%, P < .01). A nonstatistically significant reduction in ofloxacin resistance was also observed in the hospital nursing home with AMT support (Δ = -18%, P = .06). CONCLUSIONS AND IMPLICATIONS: Our antimicrobial stewardship program resulted in a decrease in resistance to FLQ among urinary Enterobacteriaceae isolated from nursing home residents. The support of an AMT along with continuous training of the coordinating physician seems to be an important component to ensure efficacy of the intervention.

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression that suggest diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A distinct phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-ß and low IFN-α production and activity), which was associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor nuclear factor-κB and characterized by increased tumor necrosis factor-α and interleukin-6 production and signaling. These data suggest that type I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

Clinical and microbiological profiles of community-acquired and nosocomial intra-abdominal infections: results of the French prospective, observational EBIIA study.

OBJECTIVES: The EBIIA (Etude épidémiologique Bactério-clinique des Infections Intra-Abdominales) study was designed to describe the clinical, microbiological and resistance profiles of community-acquired and nosocomial intra-abdominal infections (IAIs). PATIENTS AND METHODS: From January to July 2005, patients undergoing surgery/interventional drainage for IAIs with a positive microbiological culture were included by 25 French centres. The primary endpoint was the epidemiology of the microorganisms and their resistance to antibiotics. Multivariate analysis was carried out using stepwise logistic regression to assess the factors predictive of death during hospitalization. RESULTS: Three hundred and thirty-one patients (234 community-acquired and 97 nosocomial) were included. The distribution of the microorganisms differed according to the type of infection. Carbapenems and amikacin were the most active agents in vitro against Enterobacteriaceae in both community-acquired and nosocomial infections. Against Pseudomonas aeruginosa, amikacin, imipenem, ceftazidime and ciprofloxacin were the most active agents in community-acquired infections, while imipenem, cefepime and amikacin were the most active in nosocomial cases. Against the Gram-positive bacteria, vancomycin and teicoplanin were the most active in both infections. Against anaerobic bacteria, the most active agents were metronidazole and carbapenems in both groups. Empirical antibiotic therapy adequately targeted the pathogens for 63% of community-acquired and 64% of nosocomial peritonitis. The presence of one or more co-morbidities [odds ratio (OR) = 3.17; P = 0.007], one or more severity criteria (OR = 4.90; P < 0.001) and generalized peritonitis (OR = 3.17; P = 0.006) were predictive of death. CONCLUSIONS: The principal results of EBIIA are a higher diversity of microorganisms isolated in nosocomial infections and decreased susceptibility among these strains. Despite this, the adequacy of treatment is comparable in the two groups.

Epidemiology, management, and prognosis of secondary non-postoperative peritonitis: a French prospective observational multicenter study.

BACKGROUND: Despite improvements in treatment, secondary peritonitis still is associated with high morbidity and mortality rates. Better knowledge of real-life clinical practice might improve management. METHODS: Prospective, observational study (January-June 2005) of 841 patients with non-postoperative secondary peritonitis. RESULTS: Peritonitis originated in the colon (32% of patients), appendix (31%), stomach/duodenum (18%), small bowel (13%), or biliary tract (6%). Most patients (78%) presented with generalized peritonitis and 26% with severe peritonitis (Simplified Acute Physiology Score [SAPS] II score>38). Among the 841 patients, 27.3% underwent laparoscopy alone; 11% underwent repeat surgery, percutaneous drainage, or both. A SAPS II score>38 and the presence of Enterococcus spp. were predictive of abdominal and non-surgical infections (odds ratio [OR]=1.84; p=0.013 and OR=2.93; p<0.0001, respectively). A SAPS II score>38 also was predictive of death (OR=10.5; p<0.0001). The overall mortality rate was high (15%). Patients receiving inappropriate initial antimicrobial therapy had significantly higher morbidity and mortality rates than patients receiving appropriate therapy (44 vs. 30%; p=0.004 and 23% vs. 14%; p=0.015, respectively). The SAPS II score and rates of severe peritonitis, morbidity, and mortality were significantly lower in patients with appendiceal peritonitis. CONCLUSIONS: Patients with non-postoperative peritonitis should be considered high risk and should receive appropriate initial therapy. The presence of Enterococcus spp. in peritoneal cultures significantly increased morbidity but not the mortality rate. Appendiceal peritonitis that was less severe and had a better prognosis than peritonitis originating in other sites should be considered a special case in future studies.

Epidemiology and Appropriateness of Antibiotic Prescribing in Severe Pneumonia After Lung Resection.

BACKGROUND: Postoperative pneumonia (POP) is a severe complication of major lung resection. The objective of this study was to describe the current epidemiology and appropriateness of antibiotic prescriptions in severe POP, 4 years after implementation of an antimicrobial stewardship program that was based on weekly multidisciplinary review of all antibiotic therapies. METHODS: This study was a retrospective analysis of a prospectively collected database. It included all cases of severe POP occurring within 30 days after major lung resection of in a 1,500-bed hospital between 2013 and 2015. Criteria for severe POP were acute respiratory failure, severe sepsis, or a rapidly extensive pulmonary infiltrate. The study collected data on incidence, clinical outcomes, and microbiological analyses. Appropriateness of antibiotic prescribing was assessed by quality indicators previously validated in the literature. RESULTS: Over the study period, 1,555 patients underwent major lung surgery. Severe POP occurred in 91 patients (5.8%; confidence interval, 4.7%; 7.0%), with a mortality rate of 9.0% (8 of 91; confidence interval, 3.0%; 14.6%). In POP with positive microbiological results, the proportion of gram-negative bacteria other than Haemophilus was 76% (50 of 66 cases). All patients (91 of 91) had respiratory samples taken within 24 hours after the start of antibiotics; empiric therapy was concordant with the guideline in 80% (69 of 86), and it was switched to pathogen-directed therapy in 74% (46 of 62). In 71 of 91 patients (78%), the antibiotic duration was up to 7 days. CONCLUSIONS: This study reported a high proportion of gram-negative bacteria in severe POP. Four years after implementation of the program, quality indicators of antibiotic prescribing were all >70%. The rate of de-escalation to pathogen-directed therapy could be improved, however.

Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey).

BACKGROUND: Bloodstream infections (BSIs) are severe infections that can be community or hospital acquired. Effects of time to appropriate treatment and impact of antimicrobial management team are discussed in terms of outcome of BSI. We sought to evaluate the impact of initial BSI management on short-term mortality. PATIENTS AND METHODS: A prospective, multicenter survey was conducted in 121 French hospitals. Participants declaring BSI during a 1-month period were included consecutively. Data on patient comorbidities, illness severity, BSI management, and resistance profile of bacterial strains were collected. Predictors of 10-day mortality were identified by multivariate regression for overall BSI, health care-related and hospital-acquired BSI. RESULTS: We included 1,952 BSIs. More than a third of them were hospital acquired (39%). Multidrug resistance was identified in 10% of cases, mainly in health care-related BSI. Empirical therapy and targeted therapy were appropriate for 61% and 94% of cases, respectively. Increased 10-day mortality was associated with severe sepsis, septic shock, increasing age, and any focus other than the urinary tract. Decreased mortality was associated with receiving at least one active antibiotic within the first 48 hours. Intervention of antimicrobial management team during the acute phase of BSI was associated with a decreased mortality at day 10 in the overall population and in health care-related BSI. CONCLUSION: Optimizing BSI management by increasing rapidity of appropriate treatment initiation may decrease short-term mortality, even in countries with low rate of multidrug-resistant organisms. Early intervention of antimicrobial management team is crucial in terms of mortality.