Community-acquired pneumonia and positive urinary antigen tests: Factors associated with targeted antibiotic therapy.

BACKGROUND: The use of rapid microbiological tests is supported by antimicrobial stewardship policies. Targeted antibiotic therapy (TAT) for community-acquired pneumonia (CAP) with positive urinary antigen test (UAT) has been associated with a favorable impact on outcome. We aimed to determine the factors associated with TAT prescription. PATIENTS AND METHODS: We conducted a retrospective multicenter study including all patients presenting with CAP and positive UAT for Streptococcus pneumoniae or Legionella pneumophila from January 2010 to December 2013. Patients presenting with aspiration pneumonia, coinfection, and neutropenia were excluded. CAP severity was assessed using the Pneumonia Severity Index (PSI). TAT was defined as the administration of amoxicillin for pneumococcal infection and either macrolides or fluoroquinolones (inactive against S. pneumoniae) for Legionella infection. RESULTS: A total of 861 patients were included, including 687 pneumococcal infections and 174 legionellosis from eight facilities and 37 medical departments. TAT was prescribed to 273 patients (32%). Four factors were found independently associated with a lower rate of TAT: a PSI score≥4 (OR 0.37), Hospital A (OR 0.41), hospitalization in the intensive care unit (OR 0.44), and cardiac comorbidities (OR 0.60). Four other factors were associated with a high rate of TAT: positive blood culture for S. pneumoniae (OR 2.32), Hospitals B (OR 2.34), E (OR 2.68), and H (OR 9.32). CONCLUSION: TAT in CAP with positive UAT was related to the hospitals as well as to patient characteristics.

Severe community-acquired pneumonia and positive urinary antigen test for S. pneumoniae: amoxicillin is associated with a favourable outcome.

Positive urinary antigen tests (UAT) for pneumococcal infection in community-acquired pneumonia (CAP) may lead to targeted antibiotic therapy. We report an audit aimed at defining the link between mortality and targeted therapy. We conducted a retrospective multicentre audit of patients with severe CAP for whom a UAT was positive for S. pneumoniae. Patients admitted from January 2010 to December 2013 to 8 medical centres (from A to H) were included. Co-morbidities were defined by the specific treatment administered before hospital care, or if the diagnosis was newly established during the hospital stay. We used the Pneumonia Severity Index (PSI) to assess disease severity. Only patients with PSI > 90 were included. Antibiotic treatments and the PSI were extracted from patients' charts. Amoxicillin had to be prescribed as a targeted antibiotic treatment or at the time of antibiotic reassessment. A total of 389 patients were included. The mean (±STD) PSI score was 128 ± 29; 38.9% of the patients had a class 5 PSI score. Intensive care was required for 36.6% of the patients. Amoxicillin was initially prescribed in 47 cases (12.1%) and in 34 cases after reassessment (8.7%). In logistic regression analysis, we found three parameters associated with mortality: being hospitalised in institution D, class 5 PSI score, and metastatic cancer. In contrast, three antibiotic regimens were protective factors, including targeted therapy: OR = 0.09, p < 0.001. In the context of severe CAP with positive UAT for S. pneumoniae, targeted therapy was associated with a reduction in mortality.

Antimicrobial stewardship policy: time to revisit the strategy?

Recent data indicate that both the overall numbers of antibiotic prescription and the frequency of multidrug-resistant bacteria are increasing significantly. These threatening features are observed, despite national antimicrobial stewardship (AMS) policies aimed at decreasing antibiotic use. AMS should also focus on the initial steps leading to antibiotic prescription. Physicians and their patients should benefit from the structured clinical pathways, the latter being adapted to regional epidemiological data and resources. Continuous evaluation of these predefined clinical paths through a computerized medical dashboard will allow a critical review and finally the optimization of medical practices. These innovative behavioural approaches for clinicians will supply precise information on the relationship among the diagnosis, therapeutics and outcome. This changing environment will carry out the adapted therapeutic procedures, and appropriate antibiotic use will inherently improve.

Prosthetic joint infection: A pluridisciplinary multi-center audit bridging quality of care and outcome.

BACKGROUND: Care to patients with prosthetic joint infections (PJI) is provided after pluridisciplinary collaboration, in particular for complex presentations. Therefore, to carry out an audit in PJI justifies using pluridisciplinary criteria. We report an audit for hip or knee PJI, with emphasis on care homogeneity, length of hospital stay (LOS) and mortality. PATIENTS AND METHODS: Fifteen criteria were chosen for quality of care: 5 diagnostic tools, 5 therapeutic aspects, and 5 pluridisciplinary criteria. Among these, 6 were chosen: surgical bacterial samples, surgical strategy, pluridisciplinary discussion, antibiotic treatment, monitoring of antibiotic toxicity, and prevention of thrombosis. They were scored on a scale to 20 points. We included PJI diagnosed between 2010 and 2012 from 6 different hospitals. PJI were defined as complex in case of severe comorbid conditions or multi-drug resistant bacteria, or the need for more than 1 surgery. RESULTS: Eighty-two PJI were included, 70 of which were complex (85%); the median score was 15, with a significant difference among hospitals: from 9 to 17.5 points, P < 0.001. The median LOS was 17 days, and not related to the criterion score; 16% of the patients required intensive care and 13% died. The cure rate was 41%, lost to follow-up 33%, and therapeutic failure 13%. Cure was associated with a higher score than an unfavorable outcome in the univariate analysis (median [range]): 16 [9-18] vs 13 [4-18], P = 0.002. CONCLUSIONS: Care to patients with PJI was heterogeneous, our quality criteria being correlated to the outcome.

Antimicrobial stewardship program and quality of antibiotic prescriptions.

OBJECTIVE: National recommendations have been issued to define which optimal organization in hospitals could improve the quality of antibiotic prescription. Our aim was to check whether there was a link between applying these national recommendations and the quality of antibiotic prescriptions. PATIENTS AND METHODS: A prospective study was carried out in three French regional hospitals (A to C), to assess how recommendations were applied. Hospital organization was measured with the ICATB score (antimicrobial stewardship index) and the appropriateness of antibiotic prescription was assessed by an audit during 1 week by two investigators, who shadowed physicians during bedside visits, in various medical and surgical departments. RESULTS: There was a considerable difference in the organization of these three hospitals in terms of computerized prescriptions, formulary restriction, availability of recommendations, and antibiotic consumption defined as delivered daily-dose. Institution A had strictly followed recommendations for hospital organization, but these were less observed in institution B and C. The prevalence of antibiotic treatment was comparable in the three hospitals, and concerned over 25% of patients. In institution A, 60% of antibiotic prescriptions were inadequate, 23% were not appropriate and 17% were optimal. In institution B, these figures reached 36%, 34%, and 34%, while in institution C they reached 25%, 55%, and 20%, respectively. CONCLUSION: There is no clear link between applying national recommendations for antibiotic prescription and optimization of hospital organization and the quality of antibiotic prescriptions.

[Epidemiology of Enterobacteriaceae producing extended-spectrum beta-lactamase in Grasse Hospital (2005-2008)]. / Epidémiologie des entérobactéries sécrétrices de bêta-lactamases à spectre étendu (E-BLSE) au centre hospitalier de Grasse (2005-2008).

BACKGROUND: The CASFM 2008 don't recommend to search a BLSE for Enterobacteriaceae (E-BLSE) having a aac(6'). So we wanted to take stock of antibiotics co-resistances in our laboratory for these bacteria. We look for the aminoglycosides and quinolones FQ. METHODS: We studies all E-BLSE isolated in our laboratory from the 1(st) six month of 2005 to the 1st six month of 2008. Only one isolate per patient were included in this study. For each bacterial strain aminoglycosides and quinolones FQ (nalidixic acid [NA], ciprofloxacin [CIP]) were tested. RESULTS: A total of 124 E-BLSE isolates were studied. Escherichia coli increases (12 to 86%) and Enterobacter spp decreases (33 to 5%). We can note an increase of sensibles strains (6 to 23%).The mainly resistance associated is the FQ resistance (CIP: 88 to 68%). The resistance of aminoglycosides is almost associated with the NA resistance (59 to 36%). The presence of aac(6') decreases (29 to 1%). CONCLUSION: BLSE are mainly produced by Escherichia coli and antibiotics coresistances change: increase sensibles strains, supremacy of FQ resistance and decrease of the aac(6').This results can have repercussions on antibiotherapy.

Oxacillinase-mediated resistance to cefepime and susceptibility to ceftazidime in Pseudomonas aeruginosa.

Pseudomonas aeruginosa clinical isolate SOF-1 was resistant to cefepime and susceptible to ceftazidime. This resistance phenotype was explained by the expression of OXA-31, which shared 98% amino acid identity with a class D beta-lactamase, OXA-1. The oxa-31 gene was located on a ca. 300-kb nonconjugative plasmid and on a class 1 integron. No additional efflux mechanism for cefepime was detected in P. aeruginosa SOF-1. Resistance to cefepime and susceptibility to ceftazidime in P. aeruginosa were conferred by OXA-1 as well.

In vivo selection of oxacillinase-mediated ceftazidime resistance in Pseudomonas aeruginosa.

Ceftazidime-susceptible and -resistant Pseudomonas aeruginosa strains were isolated from pulmonary specimens following a treatment with ceftazidime in a patient who developed a nosocomial pneumonia. The ceftazidime-susceptible and -resistant strains were clonally related and harbored a self-transferable approximately 155-kb plasmid. These isolates expressed two OXA-10-like oxacillinases, the narrow-spectrum OXA-35 and the expanded-spectrum OXA-19, respectively, differing by one amino acid substitution. This is the first example of in vivo selection of an extended-spectrum oxacillinase from a restricted-spectrum oxacillinase.

Genetic diversity of carbapenem-hydrolyzing metallo-beta-lactamases from Chryseobacterium (Flavobacterium) indologenes.

The class B carbapenem-hydrolyzing beta-lactamase IND-1 has been characterized for Chryseobacterium indologenes strain 001. With internal primers for the bla gene for IND-1 (bla(IND-1)) and an internal bla(IND-1) probe, PCR amplifications failed, while hybridization results were positive when DNA from another C. indologenes isolate, strain CIP101026, was used as a template. Thus, a bla(IND)-related gene was cloned from this C. indologenes reference strain. Sequencing of the insert of a recombinant plasmid conferring resistance to carbapenems revealed an open reading frame with a G + C content of 39.9% and coding for a 243-amino-acid preprotein named IND-2. IND-2 shared 80% amino acid identity with IND-1 and had a similar broad-spectrum resistance profile, including resistance to carbapenems. It was classified in functional subgroup 3a of class B carbapenem-hydrolyzing beta-lactamases. IND-1 and IND-2, despite their genetic diversity, possessed similar kinetic parameters, except that ceftazidime was hydrolyzed less by IND-2. To obtain the entire bla(IND)-related gene sequences of eight other C. indologenes isolates, PCR was performed using internal and external primers, followed by inverse PCR techniques. The likely chromosome-mediated metallo-beta-lactamases of the 10 C. indologenes isolates were divided into several groups and subgroups. IND-1, IND-2, IND-2a, IND-3, and IND-4 shared 77 to 99% amino acid identity.

Efficacies of imipenem, meropenem, cefepime, and ceftazidime in rats with experimental pneumonia due to a carbapenem-hydrolyzing beta-lactamase-producing strain of Enterobacter cloacae.

The antibacterial activities of imipenem-cilastatin, meropenem-cilastatin, cefepime and ceftazidime against Enterobacter cloacae NOR-1, which produces the carbapenem-hydrolyzing beta-lactamase NmcA and a cephalosporinase, and against one of its in vitro-obtained ceftazidime-resistant mutant were compared by using an experimental model of pneumonia with immunocompetent rats. The MICs of the beta-lactams with an inoculum of 5 log(10) CFU/ml were as follows for E. cloacae NOR-1 and its ceftazidime-resistant mutant, respectively: imipenem, 16 and 128 microg/ml, meropenem, 4 and 32 microg/ml, cefepime, <0.03 and 1 microg/ml, and ceftazidime, 1 and 512 microg/ml. The chromosomally located cephalosporinase and carbapenem-hydrolyzing beta-lactamase NmcA were inducible by cefoxitin and meropenem in E. cloacae NOR-1, and both were stably overproduced in the ceftazidime-resistant mutant. Renal impairment was induced (uranyl nitrate, 1 mg/kg of body weight) in rats to simulate the human pharmacokinetic parameters for the beta-lactams studied. Animals were intratracheally inoculated with 8.5 log(10) CFU of E. cloacae, and therapy was initiated 3 h later. At that time, animal lungs showed bilateral pneumonia containing more than 6 log(10) CFU of E. cloacae per g of tissue. Despite the relative low MIC of meropenem for E. cloacae NOR-1, the carbapenem-treated rats had no decrease in bacterial counts in their lungs 60 h after therapy onset compared to the counts for the controls, regardless of whether E. cloacae NOR-1 or its ceftazidime-resistant mutant was inoculated. A significant decrease in bacterial titers was observed for the ceftazidime-treated rats infected with E. cloacae NOR-1 only. Cefepime was the only beta-lactam tested effective as treatment against infections due to E. cloacae NOR-1 or its ceftazidime-resistant mutant.

Prognostic relevance of a scoring system based on clinical and biological parameters in early chronic lymphocytic leukemia.

INTRODUCTION: Among patients with indolent form of B-cell chronic lymphocytic leukemia, some of them will progress into more advanced stages. To better define this subpopulation of patients, we attempted to define some parameters capable of predicting a pejorative clinical outcome. MATERIALS AND METHODS: Eighty-eight previously untreated patients with B-cell chronic lymphocytic leukemia in Binet stage A were analysed to study the prognostic value of simple serological variables: soluble CD23 (sCD23), beta2 microglobulin (beta2m), lactate-dehydrogenase activities and albumin level. Results were compared to other conventional clinical and biological parameters by univariate and multivariate statistical analysis. RESULTS: Our data show that: (1) among those studied, sCD23 >50 u/ml was the only serological significant parameter clearly correlated with disease progression and (2) stage A" patients (hemoglobin level between 100 and 120 g/l and/or lymphocytosis >30.10(9)/l), axillary lymph nodes and hypogammaglobulinemia were found to be other variables associated with a pejorative outcome. These four variables enabled the establishment of a scoring system, capable of predicting disease progression since 66% of the patients with a score < or =2 are going to evolve into advanced stages vs 12% with a score <2. Furthermore, the time to progression is shortened when the score is increasing. CONCLUSION: Our findings show the prognostic relevance of a scoring system including sCD23 level. This score could be taken into account in the treatment strategy of B-cell chronic lymphocytic leukemia.

Treatment of experimental pneumonia in rats caused by a PER-1 extended-spectrum beta-lactamase-producing strain of Pseudomonas aeruginosa.

The antibacterial activity of imipenem, cefepime and piperacillin-tazobactam alone or in combination with amikacin against a Pseudomonas aeruginosa strain producing an extended-spectrum beta-lactamase (PER-1) were compared using an experimental model of pneumonia in non-leucopenic rats. Animals were infected intratracheally with 8.0 +/- 0.4 log10 cfu of P. aeruginosa, and therapy was initiated 3 h later, by which time animal lungs showed bilateral pneumonia containing >7 log10 P. aeruginosa cfu/g of tissue. Since rats eliminate antibiotics much more rapidly than humans, renal impairment was induced in all animals to simulate the pharmacokinetic parameters of humans. MICs determined using an inoculum of 4 log10 cfu/mL were as follows: imipenem, 1 mg/L; cefepime, 8 mg/L; piperacillin-tazobactam, 32 mg/L; and amikacin, 16 mg/L. A noticeable inoculum effect was observed with the four antimicrobial agents tested, which was greatest for cefepime and piperacillin-tazobactam. In-vitro studies indicated that imipenem was the beta-lactam with the greatest bactericidal effect and that amikacin was synergic only in combination with cefepime and imipenem. Cefepime and piperacillin-tazobactam alone failed to decrease bacterial counts in the rats' lungs 60 h after therapy onset, whereas imipenem and, to a lesser extent, amikacin significantly reduced the number of viable microorganisms. Combination of amikacin with any of the three beta-lactams tested was synergic, despite a high amikacin MIC for the infecting strain. These results paralleled our in-vitro data showing a marked inoculum effect for cefepime and piperacillin-tazobactam. Based on the results of this study, the best treatment for infections caused by this type of extended-spectrum beta-lactamase-possessing strain would be imipenem plus amikacin.

Molecular characterization of a carbapenem-hydrolyzing beta-lactamase from Chryseobacterium (Flavobacterium) indologenes.

Chryseobacterium (Flavobacterium) indologenes 001 clinical strain was resistant to several beta-lactam classes including carbapenems. Shotgun cloning experiments of Sau3AI restricted genomic DNA of C. indologenes 001 into pBKCMV cloning vector followed by transformation into Escherichia coli DH10B gave one recombinant plasmid possessing a 4.2-kb DNA insert. It encoded a pI 7.2 beta-lactamase of 239 amino acids (IND-1) which is a metallo-enzyme with a broad spectrum beta-lactam hydrolysis profile. This class B carbapenem-hydrolyzing beta-lactamase shares the highest identity (43%) with BlaB from C. meningosepticum, thus showing heterogeneity of carbapenem-hydrolyzing beta-lactamases in Chryseobacterium spp.

Efficacies of cefepime, ceftazidime, and imipenem alone or in combination with amikacin in rats with experimental pneumonia due to ceftazidime-susceptible or -resistant Enterobacter cloacae strains.

The antibacterial activities of human regimens of cefepime, ceftazidime, and imipenem alone or in combination with amikacin against an isogenic pair of Enterobacter cloacae strains (wild type and its corresponding derepressed cephalosporinase mutant) were compared by using our nonlethal model of pneumonia with 180 immunocompetent rats. Compared with untreated animals, all beta-lactam-treated rats, except those inoculated with the mutant isolate and receiving ceftazidime, had significantly lower bacterial counts in their lungs 60 h after the onset of therapy. Although the combination of a beta-lactam and amikacin was more bactericidal than each corresponding antimicrobial agent alone, true synergy was noted only with cefepime and imipenem against the constitutive derepressed strain.