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We investigated links between antimicrobial resistance in community-onset bacteremia and 1-year bacteremia recurrence by using the clinical data warehouse of Europe's largest university hospital group in France. We included adult patients hospitalized with an incident community-onset Staphylococcus aureus, Escherichia coli, or Klebsiella spp. bacteremia during 2017-2019. We assessed risk factors of 1-year recurrence using Fine-Gray regression models. Of the 3,617 patients included, 291 (8.0%) had >1 recurrence episode. Third-generation cephalosporin (3GC)-resistance was significantly associated with increased recurrence risk after incident Klebsiella spp. (hazard ratio 3.91 [95% CI 2.32-6.59]) or E. coli (hazard ratio 2.35 [95% CI 1.50-3.68]) bacteremia. Methicillin resistance in S. aureus bacteremia had no effect on recurrence risk. Although several underlying conditions and infection sources increased recurrence risk, 3GC-resistant Klebsiella spp. was associated with the greatest increase. These results demonstrate a new facet to illness induced by 3GC-resistant Klebsiella spp. and E. coli in the community setting.

Background: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database., Methods: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex., Results: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB., Conclusions: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.

Antibiotic stewardship requires clear insight into antibiotic overuse and the syndromes that lead to prescription. The aim of this study was to estimate the proportion of antibiotic prescriptions attributable to acute lower respiratory tract infections (LRTIs) during the cold season. Using individual data from the French National Health Insurance (NHI) database, weekly time series were constructed of outpatient antibiotic (beta-lactams and macrolides) prescriptions between January 2010 and December 2017. Time series were also constructed of tenth edition of the International Classification of Diseases (ICD-10) discharge diagnoses from a national network of emergency departments (EDs), stratified by specific syndromes (pneumonia, bronchitis, bronchiolitis and influenza-like illness). The number of outpatient antibiotic prescriptions attributable to these syndromes during the cold season in France was modeled and estimated for the entire population, young children (≤5 years) and the elderly (≥75 years). LRTIs accounted for 40% (95% confidence interval [95% CI]: 29, 52) of outpatient antibiotic use during the cold season for the entire population, including 23% (95% CI: 13, 33) and 17% (95% CI: 13, 22) for bacterial and viral infections, respectively. In children and the elderly, viral LRTIs were the reason for 38% (95% CI: 31, 46) and 20% (95% CI: 16, 25) of outpatient antibiotic use, respectively (with bronchiolitis accountable for half of use in young children). In the entire population and in children, respectively, outpatient antibiotic overuse attributable to viral LRTIs was estimated to be 289 (95% CI: 221, 374) and 1588 (95% CI: 1295, 1922) prescriptions per 100 000 inhabitants per week. These results highlight the major role of viral infections in driving antibiotic prescriptions, particularly in young children., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim was to quantify the effects of selective digestive tract decontamination (SDD) consisting of a mouth paste and gastro-enteral suspension, selective oropharyngeal decontamination with a mouth paste (SOD) and 1-2% chlorhexidine (CHX) mouthwash on eradication and acquisition of carriage of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and carbapenem-resistant Gram-negative bacteria (CR-GNB) in Intensive Care Unit (ICU) patients., Methods: This was a nested cohort study within a cluster-randomized cross-over trial in six European countries and 13 ICUs with 8665 patients. Eradication and acquisition during ICU stay of 3GCR-E and CR-GNB were investigated separately in the rectum and respiratory tract for the three interventions and compared with standard care (SC) using Cox-regression competing events analyses., Results: Adjusted cause specific hazard ratios (CSHR) for eradication of rectal carriage for SDD were 1.76 (95% CI 1.31-2.36) for 3GCR-E and 3.17 (95% CI 1.60-6.29) for CR-GNB compared with SC. For the respiratory tract, adjusted CSHR for eradication of 3GCR-E were 1.47 (0.98-2.20) for SDD and 1.38 (0.92-2.06) for SOD compared with SC, and for eradication of CR-GNB these were 0.77 (0.41- 1.45) for SDD and 0.81 (0.44-1.51) for SOD, compared with SC. Adjusted CSHRs for acquisition of rectal carriage during SDD (compared with SC) were 0.51 (0.40-0.64) for 3GCR-E and of 0.56 (0.40-0.78) for CR-GNB. Adjusted CSHRs for acquiring respiratory tract carriage with 3GCR-E compared with SC were 0.38 (0.28-0.50) for SDD and 0.55 (0.42-0.71) for SOD, and for CR-GNB 0.46 (0.33-0.64) during SDD and 0.60 (0.44-0.81) during SOD, respectively. SOD was not associated with eradication or acquisition of 3GCR-E and CR-GNB in the rectum., Conclusions: Among mechanically ventilated ICU patients, SDD was associated with more eradication and less acquisition of 3GCR-E and CR-GNB in the rectum than SC. SDD and SOD were associated with less acquisition of both 3GCR-E and CR-GNB than SC in the respiratory tract., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: Antimicrobial resistance (AMR) has become one of the biggest threats to global public health given its association with mortality, morbidity and cost of health care. However, little is known on the economic burden of hospitalization attributable to AMR from a public health insurance perspective. We assessed the excess costs to the French public health insurance system attributable to AMR infections in hospitals., Methods: Bacterial infectious disease-related hospitalizations were extracted from the National health data information system for all stays occurring in 2015. Bacterial infections, strains, and microbial resistance were identified by specific French ICD-10 codes. Information about health care expenditure, co-morbidities and demographic characteristics (i.e. gender, age) are provided. We used a matched case-control approach to determine the excess of reimbursements paid to stays with AMR compared to stays with an infection without resistance. Cases and controls were matched on gender, age, Charlson comorbidity index, category of infection, infection as principal diagnosis (two classes), microorganism and hospital status. The overall AMR cost was extrapolated to stays with AMR and excluded from the sample (multiple infections), and a second extrapolation was performed to consider stays with unknown resistance status., Results: The final sample included 52,921 matched-pairs (98.2% cases). Our results suggest that AMR overall cost reached EUR109.3 million in France with a mean of EUR1103 per stay; extrapolation to the entire database shows that the overall cost could potentially reach EUR287.1 million if all cases would be identified. The mean excess length of hospital stay attributable to AMR was estimated at 1.6 days., Conclusion: AMR causes substantial cost burden in France for the public health insurance. Our study confirms the need to reinforce programs to prevent AMR infection and thereby reduce their economic burden.

Defined daily doses (DDD) are the gold standard indicator for quantifying prescriptions. Since 2014, the European Centre for Disease Prevention and Control (ECDC) has also been using the number of packages per 1,000 inhabitants per day (ipd), as a surrogate for prescriptions, to report antibiotic consumption in the community and to perform comparisons between European Union (EU) countries participating in the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). In 2015, consumption was reported to range across Europe from 1.0 to 4.7 packages per 1,000 ipd. Our analysis showed that consumption of antibiotics for systemic use per 1,000 ipd was on average 1.3 times greater in France than in Belgium when considering prescriptions in the numerator, 2.5 times greater when considering packages and 1.2 times greater when considering DDD. As long as the same metrics are used over time, antibiotic consumption data aggregated and disseminated by ECDC are useful for assessing temporal trends at the European level and within individual countries; these data may also be used for benchmarking across EU countries. While DDD - although imperfect - are the most widely accepted metric for this purpose, antibiotic packages do not appear suitable for comparisons between countries and may be misleading.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases., Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality., Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used., Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P  =   0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P  =   0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P  =   0.02]., Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Prudent antibiotic use in response to the antimicrobial resistance challenges. Appropriate antimicrobial use and hospital infection control are the two pillars on which control of antimicrobial resistance relies. Components of prudent antimicrobial prescribing in the hospital setting include : 1) an accurate microbiological diagnosis of the infection treated using appropriate microbiological samplings before initiating therapy, while avoiding treatment of patients only colonised ; 2) reappraisal of therapy at 48 to 72 h, considering de-escalation and considering PK/PD parameters; 3) reappraisal of therapy in between the 5th and 7th day, giving consideration to shortening the duration of therapy to the minimum effective length. Local epidemiology is also important to consider, especially in high-risk units. Antimicrobial stewardship teams have an important role to play in the overall fight against antimicrobial resistance in hospitals, notably regarding good prescribing of "critically important" antibiotics., Competing Interests: C. Brun-Buisson déclare avoir un lien d’intérêts en raison de sa fonction de délégué à l’antibiorésistance au ministère des Affaires sociales et de la Santé.

In a 2008-2011 survey, 17,945 patients in 18 hospital units in Europe and Israel were screened for carriage of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae, resulting in identification of 124 positive patients. The isolates were dominated by Klebsiella pneumoniae sequence type 258 (ST258) KPC-2 and ST512 KPC-3, mainly from Greece and Italy, respectively, whereas Israeli isolates were of diverse species, clones, and KPC variants. Various blaKPC platforms were observed, among which IncFIIK-FIBK plasmids with blaKPC-2/-3 genes in the Tn4401a transposon prevailed., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Objectives: The objective of this study was to examine Klebsiella oxytoca clonal and phylogenetic diversity, based on an international collection of carriage isolates non-susceptible to expanded-spectrum cephalosporins (ESCs)., Methods: The study material comprised 68 rectal carriage K. oxytoca isolates non-susceptible to ESCs recovered in 2008-11 from patients in 14 hospitals across Europe and Israel. ESC resistance was tested phenotypically; genes encoding ESBLs, AmpC cephalosporinases and carbapenemases were amplified and sequenced. The isolates were typed by PFGE and MLST, followed by sequencing of blaOXY genes., Results: MLST and PFGE distinguished 34 STs and 47 pulsotypes among the isolates, respectively. Six STs were split into several pulsotypes each. Five STs were more prevalent (n = 2-9) and occurred in several countries each, including ST2, ST9 and ST141, which belong to a growing international clonal complex (CC), CC2. Four phylogenetic lineages were distinguished, each with another type of chromosomal OXY-type β-lactamase. Three of these, with OXY-1/-5, OXY-2 types and OXY-4, corresponded to previously described phylogroups KoI, KoII and KoIV, respectively. A single isolate from Israel represented a distinct lineage with a newly defined OXY-7 type. The phylogroups showed interesting differences in mechanisms of ESC resistance; KoI strains rarely overexpressed the OXY enzymes but commonly produced ESBLs, whereas KoII strains often were OXY hyperproducers and carried ESBLs much less frequently. AmpCs (DHA-1) and carbapenemases (VIM-1) occurred sporadically., Conclusions: The study confirmed the high genetic diversity of the collection of K. oxytoca ESC-non-susceptible isolates, composed of phylogroups with distinct types of OXY-type β-lactamases, and revealed some STs of broad geographical distribution., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Empirical broad spectrum antimicrobial therapy prescribed in life-threatening situations should be de-escalated to mitigate the risk of resistance emergence. Definitions of de-escalation (DE) vary among studies, thereby biasing their results. The aim of this study was to provide a consensus definition of DE and to establish a ranking of β-lactam according to both their spectra and their ecological consequences. Twenty-eight experts from intensive care, infectious disease and clinical microbiology were consulted using the Delphi method (four successive questionnaires) from July to November 2013. More than 70% of similar answers to a question were necessary to reach a consensus. According to our consensus definition, DE purpose was to reduce both the spectrum of antimicrobial therapy and the selective pressure on microbiota. DE included switching from combination to monotherapy. A six-rank consensual classification of β-lactams allowing gradation of DE was established. The group was unable to differentiate ecological consequences of molecules included in group 4, i.e. piperacillin/tazobactam, ticarcillin/clavulanic acid, fourth-generation cephalosporin and antipseudomonal third-generation cephalosporin. Furthermore, no consensus was reached on the delay within which DE should be performed and on whether or not the shortening of antibiotic therapy duration should be included in DE definition. This study provides a consensual ranking of β-lactams according to their global ecological consequences that may be helpful in future studies on DE. However, this work also underlines the difficulties of reaching a consensus on the relative ecological impact of each individual drug and on the timing of DE., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study aimed to determine the clinical course of patients and the quality of antibiotic use using a systematic and unsolicited post-prescription antibiotic review. Seven hundred and fifty-three adult patients receiving antibiotic therapy for 3-5 days were randomized to receive either a post-prescription review by the infectious disease physician (IDP), followed by a recommendation to the attending physician to modify the prescription when appropriate, or no systematic review of the prescription. In the intervention group, 63.3% of prescriptions prompted IDP recommendations, which were mostly followed by ward physicians (90.3%). Early antibiotic modifications were more frequent in the intervention group (57.1% vs. 25.7%, p <0.0001), including stopping therapy, shortening duration and de-escalating broad-spectrum antibiotics. IDP intervention led to a significant reduction of the median [IQR] duration of antibiotic therapy (6 [4-9] vs. 7 days [5-9], p <0.0001). In-hospital mortality, ICU admission and new course of antibiotic therapy rates did not differ between the two groups. Fewer patients in the intervention group were readmitted for relapsing infection (3.4% vs. 7.9%, p 0.01). There was a trend for a shorter length of hospital stay in patients suffering from community-acquired infections in the intervention group (5 days [3-10] vs. 6 days [3-14], p 0.06). This study provides clinical evidence that a post-prescription antibiotic review followed by unsolicited IDP advice is effective in reducing antibiotic exposure of patients and increasing the quality of antibiotic use, and may reduce hospital stay and relapsing infection rates, with no adverse effects on other patient outcomes., (© 2012 The Authors Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

The purpose of this investigation was to describe the impact of an early review of antibiotic prescriptions in a hospital using unsolicited infectious disease physician (IDP) counselling, identify areas for improvement and examine factors associated with physicians' non-compliance. The prescriptions of 15 selected antibiotics from surgical or medical wards were screened daily and reviewed between days 3 and 5 by a single IDP during an 8-month period to identify those likely needing counselling. Improved antibiotic use was sought by encouraging ward physicians to withdraw or de-escalate therapy, promoting oral switch or reducing the duration of therapy whenever appropriate. Variables potentially associated with IDP counselling and physicians' non-compliance were tested using bivariate analysis and then entered in a logistic regression model. Among 857 prescriptions analysed, 54.6 % prompted unsolicited counselling, mostly for stopping therapy (18.8 %), reducing its duration (18.0 %) or de-escalation (13.0 %). Variables independently associated with IDP counselling included antibiotic combination (adjusted odds ratio [aOR], 5.27 [95 % confidence interval (CI), 1.80-15.45]; p = 0.002), non-clinically documented infection (aOR, 4.98 [95 % CI, 2.81-8.82]; p < 0.001) and microbiologically documented infection (aOR, 2.04 [95 % CI, 1.51-2.75]; p < 0.001). The physicians' compliance rate was 77.3 %. Variables independently associated with physicians' non-compliance to the IDP recommendation were the surgical speciality of the ward physician (aOR, 1.91 [95 % CI, 1.17-3.12]; p = 0.009) and advice to reduce the duration of therapy (aOR, 1.88 [95 % CI, 1.12-3.15]; p = 0.017). An unsolicited post-prescription antibiotic review can be successfully implemented with a high rate of physicians' compliance. Areas for targeting improvement measures include prescriptions in surgical wards and shortening the duration of therapy.

Community-associated methicillin-resistant S. aureus (CA-MRSA) is increasingly common in hospitals, with potentially serious consequences. The aim of this study was to assess the impact of antibiotic prescription patterns on the selection of CA-MRSA within hospitals, in a context of competition with other circulating staphylococcal strains, including methicillin-sensitive (MSSA) and hospital-associated methicillin-resistant (HA-MRSA) strains. We developed a computerized agent-based model of S. aureus transmission in a hospital ward in which CA-MRSA, MSSA, and HA-MRSA strains may cocirculate. We investigated a wide range of antibiotic prescription patterns in both intensive care units (ICUs) and general wards, and we studied how differences in antibiotic exposure may explain observed variations in the success of CA-MRSA invasion in the hospitals of several European countries and of the United States. Model predictions underlined the influence of antibiotic prescription patterns on CA-MRSA spread in hospitals, especially in the ICU, where the endemic prevalence of CA-MRSA carriage can range from 3% to 20%, depending on the simulated prescription pattern. Large antibiotic exposure with drugs effective against MSSA but not MRSA was found to promote invasion by CA-MRSA. We also found that, should CA-MRSA acquire fluoroquinolone resistance, a major increase in CA-MRSA prevalence could ensue in hospitals worldwide. Controlling the spread of highly community-prevalent CA-MRSA within hospitals is a challenge. This study demonstrates that antibiotic exposure strategies could participate in this control. This is all the more important in wards such as ICUs, which may play the role of incubators, promoting CA-MRSA selection in hospitals.

Objectives: The unsolicited and systematic evaluation of positive blood cultures (pBC) after laboratory report by a single infectious disease specialist (IDS) was evaluated during one year, using a computer-generated alert by the laboratory. The main objectives of IDS counselling were to improve antibiotic use for bloodstream infection (i.e., initiating or modifying therapy) and to stop unjustified therapy for contaminated pBC., Methods: During the first part of the study (4 months), all pBC in patients from ICUs, medical and surgical wards were analyzed. After an interim analysis, only pBC from medical and surgical wards were evaluated during the second part (8 months)., Results: Overall, 1090 episodes of pBC (representing 866 patients) were evaluated and classified as bloodstream infection (65.5%), contamination (29%) or undetermined (5.5%). Forty-three percent of episodes prompted IDS counselling, including initiation (5%), modification (27.5%), withdrawal (3.5%) and diagnosis workup (5%). Restricting the evaluation to medical and surgical wards increased the rate of counselling (61.2% vs. 27.7%, P<0.0001), notably for de-escalating (20% vs. 8%, P<0.0001), initiating (9% vs. 2%, P<0.0001), oral switch (6% vs. 2%, P<0.0001), withdrawing (5% vs. 2%, P=0.002) or reducing the duration of therapy (5% vs. 2%, P=0.002)., Discussion and Conclusions: In complement to the laboratory report, a computer-generated alert used by the IDS was useful for the management of pBC in hospital. The impact of IDS counselling was more effective when the evaluation was restricted to medical and surgical wards., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objectives: Encouraging reassessment of intravenous antibiotic therapy at days 3-4 is an important step in the management of patients and may be done by delivering a questionnaire or through systematic infectious disease physician (IDP) advice to prescribers., Patients and Methods: In this before-and-after study, prescriptions of 13 selected intravenous antibiotics from surgical or medical wards were screened from a computer-generated listing and prospectively included. Three strategies were compared over three consecutive 8 week periods: conventional management by the attending physician (control group); distribution of a questionnaire to the physician (questionnaire group); or distribution of the questionnaire followed by IDP advice (Q-IDP group). The primary outcome was the percentage of modifications of antibiotic therapy at day 4, including withdrawal of therapy, de-escalation, oral switch or reducing the planned duration of therapy., Results: Overall, 402 prescriptions were included. At day 4, 48.9% and 54.5% of prescriptions were modified in the control and questionnaire groups, respectively (P = 0.35). In contrast, more prescriptions (66.2%) were modified in the Q-IDP group as compared with the control group (P = 0.004). Stopping therapy in the absence of apparent bacterial infection occurred significantly more often in the Q-IDP group than in the control (P < 0.0001) or questionnaire groups (P = 0.002)., Conclusions: This study shows a modest impact of only distributing a questionnaire aimed at reminding physicians to reassess therapy, whereas systematic IDP intervention improves the modification rate.

Background: Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting., Methods: In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667., Findings: Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001)., Interpretation: A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes., Funding: Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Little is known about the incidence of inadequate treatment of severe Staphylococcus aureus infection in Europe. We aimed to evaluate the adequacy of antibiotic therapy for S. aureus bacteremia (SAB), to identify determinants of inadequate treatment, and to determine the effect of inadequate treatment on patient outcome in a representative selection of hospitals in 9 Western European countries., Methods: In this retrospective cohort study, all adult patients with SAB (due to methicillin-susceptible S. aureus [MSSA] or methicillin-resistant S. aureus [MRSA]) who were admitted to 60 randomly selected hospitals from 1 November 2007 through 31 December 2007 were included. Adequate antimicrobial therapy was defined as intravenous administration of at least 1 antibiotic to which the isolate showed in vitro susceptibility that was initiated within 2 days after onset of SAB., Results: A total of 334 SAB episodes (257 due to MSSA and 77 due to MRSA) were included. Ninety-four patients (28%) received inadequate empirical therapy (21% in the MSSA group and 52% in the MRSA group). Both length of stay before SAB onset and methicillin-resistant infection were associated with inadequate therapy, with adjusted odds ratios (ORs) of 1.01 (95% confidence interval [CI], 1.00-1.03) and 3.7 (95% CI, 2.2-6.4), respectively. Age (OR, 1.06; 95% CI, 1.03-1.10), Charlson comorbidity score (OR, 2.1; 95% CI, 1.2-3.6), severe sepsis or septic shock (OR, 2.7; 95% CI, 1.5-4.8), and intensive care unit stay at onset of SAB (OR, 2.9; 95% CI, 1.5-5.6) but not inadequate treatment (OR, 0.7; 95% CI, 0.4-1.3) were associated with increased 30-day mortality., Conclusion: Inadequate empirical antimicrobial therapy for SAB is common in Western Europe and is strongly associated with infection caused by MRSA. In this study, inadequate treatment was not associated with increased 30-day mortality rates.

Objectives: Although medical-surgical therapy can reduce mortality in patients with infective endocarditis (IE), the optimal timing of surgery remains controversial. We evaluated the influence of preoperative antimicrobial therapy duration on positivity of valve culture and outcome., Methods: We retrospectively studied 94 consecutive patients admitted in our intensive care unit (ICU) and operated before completion of standard antimicrobial therapy., Results: Of 90 valves cultured, 46 were positive. In univariate analysis, time between diagnosis and surgery as well as duration of adequate therapy before surgery was shorter in patients with positive valve cultures as compared to those with negative cultures. A preoperative duration of adequate therapy > or =7 days was strongly associated with negative valve cultures (76% vs. 22%, P<0.001). Logistic regression analysis identified duration of preoperative adequate antimicrobial therapy as an independent risk factor for positive valve culture. However, there was no significant difference between patients with positive or negative valve culture regarding the occurrence of complications, ICU and hospital length of stay, hospital and long-term mortality, endocarditis relapse and reinfection, as well as treatment failure., Conclusions: Although the duration of adequate preoperative antimicrobial therapy is associated with the positivity of valve culture, the latter factor does not influence short- or long-term outcome.

Objectives: The aim of this study was to measure the impact on antibiotic use of a computer-generated alert prompting post-prescription review and direct counselling in hospital wards., Methods: A computer-generated alert on new prescriptions of 15 antibiotics was reviewed weekly by an infectious disease physician for 41 weeks. During the first 6 months of the study, criteria selected for potential intervention were: (i) a planned duration of treatment of > or =10 days; (ii) discordance between the spectrum of the prescribed antibiotic and available microbiological results; or (iii) prescriptions of broad-spectrum beta-lactams, fluoroquinolones, glycopeptides or linezolid. During the following 5 months, the alert was restricted to any prescription of the 15 antibiotics in the 9 wards where overall antibiotic use had not decreased in the past year., Results: We analysed 2385 prescriptions, 932 (39%) of which generated an alert for potential intervention. Among the latter, 482 (51.7%) prescriptions prompted direct counselling, mainly for shortening the planned duration of therapy (18.9%), withdrawing antibiotics (16.2%) or streamlining therapy (15.5%). The attending physicians' compliance with the recommendations was 80%. The overall median (interquartile range) days of therapy prescribed by the attending physicians was reduced from an initial duration of 8 (7-14) to 7 (6-11) days (P < 0.0001), resulting in 26.5% less antibiotic days prescribed. The time required for the intervention was 6 h per week., Conclusions: This computer-prompted post-prescription review led physicians to modify one half of the antibiotic courses initially prescribed and was well accepted by the majority, although they had not requested counselling.

Purpose of Review: Antibiotic stewardship is designed to optimize antimicrobial therapy administered to hospitalized patients, to ensure cost-effective therapy and improve patients' outcome while containing bacterial resistance. Current data on the development of effective programmes, including guidelines for their implementation, have demonstrated some efficacy and controversies are reviewed., Recent Findings: Guidelines have been recently issued for the development and implementation of active antibiotic stewardship programmes in hospitals. A multidisciplinary team including at least an infectious disease physician and a clinical pharmacist is required. Multiple strategies are available, including prospective audit with feedback to the provider, education and antimicrobial restriction. Interventions have shown a positive effect on optimization of antimicrobial use, reduced costs and bacterial resistance, but studies showing improvement in patient outcomes are sparse. Results of studies may be confounded by several factors, mainly due to their before-after design and lack of control for cointerventions., Summary: Combined with an effective infection control programme, antibiotic stewardship can help contain antimicrobial resistance. Studies demonstrating improvement of patients' outcomes are needed to increase acceptance by a broader audience of physicians. A proactive strategy of prospective auditing with direct counsels and feedback to the prescriber, ensuring systematic reassessment of ongoing therapy, appears most useful.

Objective: To characterize empiric antibiotic use in patients with suspected nosocomial ICU-acquired infections (NI), and determine the impact of prolonged therapy in the absence of infection., Design and Setting: Multicenter prospective cohort, with eight medical-surgical ICUs in North America and Europe., Patients: 195 patients with suspected NI., Methods: The diagnosis of NI was adjudicated by a blinded Clinical Evaluation Committee using retrospective review of clinical, radiological, and culture data., Results: Empiric antibiotics were prescribed for 143 of 195 (73.3%) patients with suspected NI; only 39 of 195 (20.0%) were adjudicated as being infected. Infection rates were similar in patients who did (26 of 143, 18.2%), or did not (13 of 52, 25.0%) receive empiric therapy (p = 0.3). Empiric antibiotics were continued for more than 4 days in 56 of 95 (59.0%) patients without adjudicated NI. Factors associated with continued empiric therapy were increased age (p = 0.02), ongoing SIRS (p = 0.03), and hospital (p = 0.004). Patients without NI who received empiric antibiotics for longer than 4 days had increased 28-day mortality (18 of 56, 32.1%), compared with those whose antibiotics were discontinued (3 of 39, 7.7%; OR = 5.7, 95% CI 1.5-20.9, p = 0.005). When the influence of age, admission diagnosis, vasopressor use, and multiple organ dysfunction was controlled by multivariable analysis, prolonged empiric therapy was not independently associated with mortality (OR = 3.8, 95% CI 0.9-15.5, p = 0.07)., Conclusions: Empiric antibiotics were initiated four times more often than NI was confirmed, and frequently continued in the absence of infection. We found no evidence that prolonged use of empiric antibiotics improved outcome for ICU patients, but rather a suggestion that the practice may be harmful.

Objectives: Many factors are involved in the appropriate use of aminoglycosides, such as modalities of administration, drug levels monitoring and duration of treatment. We assessed prospectively the impact of an antibiotic control team on the appropriateness of prescriptions., Methods: After a first observational audit assessing the appropriateness of prescriptions, and issuing updated recommendations, we performed an interventional audit, where an antibiotic control team provided counselling when prescriptions were considered inappropriate. Appropriateness of prescriptions, clinical outcomes of patients and medical costs were compared between the two periods., Results: One hundred consecutive prescriptions were analysed in each period, and 32% of prescriptions were modified by the control team. As compared with the observational period, prescriptions in the intervention period were more appropriate with regard to treatment duration (73% versus 56%, P = 0.01) and drug levels monitoring (61% versus 40%, P = 0.05), and the median treatment duration was shorter (4 versus 6 days, P = 0.0002). Independent factors associated with appropriate treatment duration were hospitalization in intensive care unit [adjusted odds ratio (aOR), 4.46; 95% confidence interval (CI), 1.60-12.46], polymicrobial infection (aOR, 3.97; 1.32-11.92) and antibiotic control team intervention (aOR, 2.49; 1.27-4.87). The intervention period was associated with lower rate of nephrotoxicity (15% versus 4%, P = 0.01) and lower direct medical costs (4,039.4 Euros per 100 persons treated)., Conclusions: Aminoglycoside use was frequently associated with excessive treatment duration and incorrect drug level monitoring. Reinforcing practice guidelines through direct counselling improved the appropriateness of prescriptions.

Introduction: Intensive Care Unit (ICU) admission for acute exacerbation of chronic obstructive lung disease (COLD) is a major cause of morbidity and mortality in such patients. Although bacterial and/or viral infections are considered as the major precipitating factor, the antibiotic strategy in this setting is unclear. The potential benefit of routine antibiotic therapy in the absence of evidence of overt infection remains controversial, and has not been adequately studied in patients admitted to the ICU. To assess the benefit (or lack thereof) of routine early systemic antibiotic therapy in patients with COLD admitted to the ICU., Methods: This is a multicenter, randomized, double-blind controlled trial, comparing amoxicillin-clavulanic acid administered for 7 days to a placebo. Patients included are those with documented or suspected COLD, exclusive of other bronchial or lung disease, and admitted for acute exacerbation, in the absence of overt sepsis or broncho-pneumonia, and having no other organ failure. Patients recently hospitalized, having received antibiotics for > 24 h, or on long-term steroids will not be included. Co-interventions (bronchodilators, steroids) are controlled for. Patients will be administered the antibiotic or placebo within 24 hours of admission., Expected Results: A 20% reduction of the duration of clinical symptoms of exacerbation is expected. To this end, 520 patients are planned to be included in 15 centers in a 2-year period. Secondary end-points are the incidence of documented infection (lower respiratory tract or other sites), antibiotic use, the proportion of patients having infection with resistant bacteria, the incidence of endotracheal intubation, the duration of stay and mortality in the ICU and the hospital.

Bartonella species are emerging as an important cause of blood culture-negative endocarditis, but the optimal management of this disease has not been fully defined. We describe a case of subacute Bartonella henselae endocarditis of a prosthetic aortic valve in an immunocompetent woman that was cured with long-term antibiotic therapy alone. In addition, we demonstrate that follow-up of serologic titers against B. henselae was helpful in assessing definitive cure of the infection.

The prevalence of penicillin-nonsusceptible pneumococci is sharply divided between France (43%) and Germany (7%). These differences may be explained on different levels: antibiotic-prescribing practices for respiratory tract infections; patient-demand factors and health-belief differences; social determinants, including differing child-care practices; and differences in regulatory practices. Understanding these determinants is crucial for the success of possible interventions. Finally, we emphasize the overarching importance of a sociocultural approach to preventing antibiotic resistance in the community.

We evaluated the appropriateness of use of restricted antimicrobial agents in the context of a newly implemented order form and delivery system for restricted antimicrobial agents, using sequential prospective audits of prescriptions. Four antimicrobial agents were selected: glycopeptides (61 prescriptions), ciprofloxacin (42), piperacillin-tazobactam (42) and imipenem- cilastatin (47). The justification and adequacy of the antibiotic or combination used, reassessment of therapy and duration of treatment were appraised with reference to the clinical situation and hospital's guidelines. Of the 192 prescriptions, 30 (16%) were empirical therapy, 95 (49%) empirical and secondarily documented and 67 (35%) initially documented therapy. Overall, 73% of prescriptions conformed to guidelines, but the adequacy varied from 93% for vancomycin to only 38% for ciprofloxacin. Of 83/157 initially inadequate prescriptions, 42 (51%) were switched according to guidelines, but only 14% of ciprofloxacin prescriptions were adapted later. An intervention audit with counselling on ciprofloxacin usage increased this rate to 75%. Although implementation of the guidelines resulted in a marked reduction in overall antimicrobial costs, inappropriate antibiotic usage may persist for some drugs despite restricted access. These results emphasize the need for combined interventions using education and expert counselling, targeted to classes of antibiotic for which inappropriate usage is most common.

In a randomized trial conducted in 27 intensive care units, we compared the clinical efficacy and safety of piperacillin-tazobactam (TAZ; 4 g/0.5 g q.i.d.) and of ceftazidime (CAZ; 1 g q.i.d.), both combined with amikacin (7.5 mg/kg b.i.d.), as therapy for ventilator-associated pneumonia (VAP; acquired after > or =48 hours of mechanical ventilation). VAP was diagnosed with use of protected samples and quantitative cultures, and outcome was assessed blindly from treatment. Of 204 patients suspected of having VAP and randomized to a treatment arm of the study, 127 (64%) had bacteriologically confirmed infections, of which 37% were polymicrobial and 32% involved Pseudomonas aeruginosa; 115 patients (51 TAZ and 64 CAZ recipients) remained evaluable as per protocol. Clinical/bacteriologic cure rates (TAZ vs. CAZ, 51% vs. 36%; 95% confidence interval of difference, -0.2% to 30.2%), and 28-day mortality rates (16% vs. 20%) were similar; however, fewer bacteriologic failures occurred with TAZ (33% vs. 51%; P = .05). We conclude that the two regimens were of equivalent clinical efficacy in therapy for confirmed VAP.

ICUs are often viewed as the epicenter of bacterial resistance. Overuse of antibiotics is one factor associated with this characteristic; other such factors include overcrowding, suboptimal observance of hygienic practices, cross-transmission of resistant strains, and high susceptibility of patients housed in ICUs. Evidence is scarce that different approaches to diagnosing infections, especially of the lower respiratory tract, can influence overall patterns of antibiotic usage and resistance. However, it is likely that more antibiotics are being administered to patients with suspected respiratory tract infections when diagnosed using nonspecific techniques than when more specific techniques are being used routinely. Additionally, the evidence is mounting that prior antibiotic usage is associated with increased risk of lower respiratory tract infection (LRTI), and also of infection caused by high-risk antibiotic-resistant pathogens, which in turn are associated with higher risk of treatment failure and mortality than their susceptible counterparts. A logical approach that may partially resolve this problem is to use specific diagnostic techniques, which will result in avoiding overtreating patients with suspected LRTI.

The antibiotic therapy in septic syndrome is most often empiric. Decisions and antibiotic choices should result from a careful analysis of past history and setting (hospital-acquired infections vs community acquired infections), risk factors specific to the host, and characteristics of the suspected infections focus: direct examination of body fluid specimens should be obtained rapidly to guide the empiric choice. The choice of antibiotics should conform to usual guidelines, with the aim of a rapid bactericidal effect in blood, while attempting to avoid risks of toxicity. Changes in pharmacokinetics of drugs are usual in this context, and frequent dosing is necessary. While effective antibiotic therapy is a recognized prognostic parameter, antibiotics are only one part of therapy, besides supportive therapy of failing organs, and effective drainage or surgery of the infected focus, when feasible.

Study Objective: To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates., Design: A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3)., Setting: A medical intensive care unit of a tertiary care university hospital., Patients: Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination)., Interventions: Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit., Measurements and Main Results: Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3)., Conclusions: Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections.

Salam Abbara,1,2 Didier Guillemot,1– 3 Salma El Oualydy,4 Maeva Kos,4 Cécile Poret,5 Stéphane Breant,5 Christian Brun-Buisson,1,2 Laurence Watier1,2 1Anti-Infective Evasion and Pharmacoepidemiology Team, Inserm, UVSQ, University Paris-Saclay, CESP, Montigny-Le-Bretonneux, France; 2Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE), University Paris Cité, Paris, France; 3Public Health, Medical Information, Clinical Research, AP-HP, University Paris Saclay, Le Kremlin-Bicêtre, France; 4Plateforme des données de santé - Health Data Hub, Paris, France; 5AP-HP, Direction des Systèmes d’Information, Pôle Innovation et Données, Paris, FranceCorrespondence: Salam Abbara, Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE) Unit, 25-28 rue du Docteur Roux, Paris, 75015, France, Tel +33 1 45 68 80 00, Email salam.abbara@gmail.comPurpose: Antibiotic-resistant bacteremia is a leading global cause of infectious disease morbidity and mortality. Clinical data warehouses (CDWs) allow for the secure, real-time coupling of diverse data sources from real-world clinical settings, including care-based medical-administrative data and laboratory-based microbiological data. The main purpose of this study was to assess the contribution of CDWs in the epidemiological study of antibiotic resistance by constructing a database of bacteremia patients, BactHub, and describing their main clinico-microbiological features and outcomes.Patients and Methods: Adult patients with bacteremia hospitalized between January 1, 2016 and December 31, 2019 in 14 acute care university hospitals from the Greater Paris area were identified; their first bacteremia episode was included. Data describing patients, episodes of bacteremia, bacterial isolates, and antimicrobial resistance were structured.Results: Among 29,228 patients with bacteremia, 41% of episodes were community-onset (CO) and 59% were hospital-acquired (HA). Thirty-day and ninety-day mortality rates were 15% and 20% in CO episodes, and 18% and 36% in HA episodes. Overall resistance rates were high, including third-generation cephalosporin resistance among Klebsiella pneumoniae (CO 21%, HA 37%) and Escherichia coli (CO 13%, HA 17%), and methicillin resistance among Staphylococcus aureus (CO 11%, HA 14%). Annual incidence rates increased significantly from 2017 to 2019, from 20.0 to 20.9 to 22.1 stays with bacteremia per 1000 stays (p < 0.0001).Conclusion: The Bacthub database provides accurate clinico-microbiological data describing bacteremia across France’s largest hospital group. Data from Bacthub may inform surveillance and the clinical decision-making process for bacteremia patients, including choice of antimicrobial therapy. The database also offers opportunities for research, including analysis of hospital care pathways and significant patient outcomes such as mortality and recurrence of infection.Keywords: data warehousing, bacteremia, drug resistance, microbial, anti-bacterial agents, mortality, incidence