Efficacy of Nanoencapsulated Daptomycin in an Experimental Methicillin-Resistant Staphylococcus aureus Bone and Joint Infection Model.

Staphylococcus aureus bone infections remain a therapeutic challenge, leading to long and expensive hospitalizations. Systemic antibiotic treatments are inconsistently effective, due to insufficient penetration into the infectious site. In an osteomyelitis model, the single local administration of nanoparticle-encapsulated daptomycin allows sterilization of the infectious sites after 4 and 14 days of treatment, while daily systemic daptomycin treatment for 4 days was not effective. These results demonstrate the great potential of this local antibiotic treatment.

Withholding and withdrawing life-support in adults in emergency care: joint position paper from the French Intensive Care Society and French Society of Emergency Medicine.

For many patients, notably among elderly nursing home residents, no plans about end-of-life decisions and palliative care are made. Consequently, when these patients experience life-threatening events, decisions to withhold or withdraw life-support raise major challenges for emergency healthcare professionals. Emergency department premises are not designed for providing the psychological and technical components of end-of-life care. The continuous inflow of large numbers of patients leaves little time for detailed assessments, and emergency department staff often lack training in end-of-life issues. For prehospital medical teams (in France, the physician-staffed mobile emergency and intensive care units known as SMURs), implementing treatment withholding and withdrawal decisions that may have been made before the acute event is not the main focus. The challenge lies in circumventing the apparent contradiction between the need to make immediate decisions and the requirement to set up a complex treatment project that may lead to treatment withholding and/or withdrawal. Laws and recommendations are of little assistance for making treatment withholding and withdrawal decisions in the emergency setting. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and French Society of Emergency Medicine (Société Française de Médecine d'Urgence, SFMU) tasked a panel of emergency physicians and intensivists with developing a document to serve both as a position paper on life-support withholding and withdrawal in the emergency setting and as a guide for professionals providing emergency care. The task force based its work on the available legislation and recommendations and on a review of published studies.

Guideline-Based Clinical Assessment Versus Procalcitonin-Guided Antibiotic Use in Pneumonia: A Pragmatic Randomized Trial.

STUDY OBJECTIVE: Efforts to reduce unnecessary and unnecessarily long antibiotic treatment for community-acquired pneumonia have been attempted through use of procalcitonin and through guidelines based on serial clinical assessment. Our aim is to compare guideline-based clinical assessment- and procalcitonin algorithm-guided antibiotic use among patients with community-acquired pneumonia. METHODS: We performed a pragmatic, randomized, multicenter trial from November 2012 to April 2015 at 12 French hospitals. We included emergency department (ED) patients older than 18 years with community-acquired pneumonia. Patients were randomly assigned to either the procalcitonin-guided or clinical assessment group. In accordance with past studies, we hypothesized that serial clinical assessment would be superior to procalcitonin-guided care. The primary outcome was antibiotic duration, and secondary outcomes included rates of antibiotic duration less than or equal to 5 days, and clinical success and combined serious adverse outcomes at 30 days in the intention-to-treat population. RESULTS: Of 370 eligible patients, 285 (77%) were randomly assigned to either clinical assessment- (n=143) or procalcitonin-guided care (n=142). Median age was 67 years (range 18 to 93 years) and 40% of patients were deemed to have Pneumonia Severity Index class IV or V. Procalcitonin algorithm adherence was 76%. Antibiotic duration was not significantly different between clinical assessment- and procalcitonin-guided groups (median 9 versus 10 days, respectively). Clinical success rate was 92% in each group and serious adverse outcome rates were similar (15% versus 20%, respectively). CONCLUSION: Guideline-based serial clinical assessment did not reduce antibiotic exposure compared with procalcitonin-guided care among ED patients with community-acquired pneumonia. The strategies were similar in terms of duration of antibiotic use and clinical outcomes.

Beyond Piperacillin-Tazobactam: Cefepime and AAI101 as a Potent ß-Lactam-ß-Lactamase Inhibitor Combination.

Impeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum ß-lactamases [ESBLs]) continue to evolve and disseminate around the world. One approach to attack this problem is to develop novel therapies that will protect our current agents. AAI101 is a novel penicillanic acid sulfone ß-lactamase inhibitor similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, is in phase III of clinical development for the treatment of serious Gram-negative infections. Here, AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel. The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of ß-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, the in vivo efficacy of cefepime-AAI101 was demonstrated using a mouse septicemia model, indicating the ability of AAI101 to bolster significantly the therapeutic efficacy of cefepime in vivo The combination of AAI101 with cefepime represents a potential carbapenem-sparing treatment regimen for infections suspected to be caused by Enterobacteriaceae expressing ESBLs.

Recognition and treatment of severe sepsis in the emergency department: retrospective study in two French teaching hospitals.

BACKGROUND: Sepsis management in the Emergency Department remains a daily challenge. The Surviving Sepsis Campaign (SSC) has released three-hour bundle. The implementation of these bundles in European Emergency Departments remains poorly described. The main objective was to assess the compliance with the Severe Sepsis Campaign 3-h bundle (blood culture, lactate dosage, first dose of antibiotics and 30 ml/kg fluid challenge). Secondary objectives were the analysis of the delay of severe sepsis recognition and description of the population. METHODS: In accordance with STROBE statement, we performed a retrospective study in two French University Hospital Emergency Departments from February to August 2015. Patients admitted during the study period were screened using the electronic files of the hospital databases. Patient's files were reviewed and included in the study if they met severe sepsis criteria. Demographics, comorbities, treatments were recorded. Delays from admission to severe sepsis diagnosis, fluid loading onset and antibiotics administration were calculated. RESULTS: One hundred thirty patients were included (76 men, mean age 71 ± 14 years). Blood culture, lactate dosage, antibiotics and 30 ml/kg fluid loading were performed within 3 hours in % [95% confidence interval] 100% [96-100%], 62% [54-70%], 49% [41-58%] and 19% [13-27%], respectively. 25 patients out of 130 (19% [13-27%]) fulfilled each criteria of the 3-h bundle. The mean fluid loading volume was 18 ± 11 ml/kg. Mean delay between presentation and severe sepsis diagnosis was 200 ± 263 min, from diagnosis to fluid challenge and first antibiotic dose, 10 ± 27 min and 20 ± 55 min, respectively. CONCLUSION: Compliance with SSC 3-h bundle and delay between admission and sepsis recognition have to be improved. If confirmed by other studies, an improvement program might be deployed.

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract.

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.

Use of broad-spectrum antibiotics in French EDs: different trends for third-generation cephalosporins and fluoroquinolones.

OBJECTIVES: Third-generation cephalosporins and fluoroquinolones are particularly prone to promoting bacterial resistance. Their use in Emergency Departments (EDs) is poorly known. Our objectives were to assess the use of antibacterial agents in French EDs. METHODS: This study is a retrospective study of antibiotics delivered to the adult units of 11 EDs of French academic centres in 2012, and to six of these EDs between 2009 and 2012. RESULTS: The total antibiotic use was 66.4 defined daily doses (DDD)/1000 ED visits in 2012, and it increased between 2009 and 2012 (yearly estimate, +1.8±0.9 DDD/1000 ED visits, P=0.048). The 3GC-FQ class, which grouped third-generation cephalosporins and fluoroquinolones, accounted for 39.2% of the total antibiotic use, and the use of this class of antibiotics was highly variable among EDs (range, 31.6-49.5% of total antibiotic use). The aminopenicillin and ß-lactamase inhibitor/3GC-FQ ratio varied among EDs [median (range), 0.91 (0.52-1.25)]. Between 2009 and 2012, there was a significant decrease in the use of the 3GC-FQ class (yearly estimate, -0.8±0.4% of total antibiotic use), antipneumococcal fluoroquinolones (-0.8±0.3%) and other fluoroquinolones (-0.9%±0.3%), and there was a significant increase in the use of third-generation cephalosporins (+0.7±0.3%), aminoglycosides (+0.4±0.1%), imidazole derivatives (+0.4±0.1%) and lincosamides (+0.1±0.0%). CONCLUSION: Fluoroquinolones and third-generation cephalosporins are widely used in the ED. Their use is highly variable among EDs. Third-generation cephalosporins were increasingly used between 2009 and 2012, whereas the use of fluoroquinolones decreased. Reduced use of cephalosporins in the ED, without increasing fluoroquinolone use, should be aimed at through antibiotic stewardship programs.

ECG interpretation in Emergency Department residents: an update and e-learning as a resource to improve skills.

OBJECTIVE: ECG interpretation is a pivotal skill to acquire during residency, especially for Emergency Department (ED) residents. Previous studies reported that ECG interpretation competency among residents was rather low. However, the optimal resource to improve ECG interpretation skills remains unclear. The aim of our study was to compare two teaching modalities to improve the ECG interpretation skills of ED residents: e-learning and lecture-based courses. PARTICIPANTS AND METHODS: The participants were first-year and second-year ED residents, assigned randomly to the two groups. The ED residents were evaluated by means of a precourse test at the beginning of the study and a postcourse test after the e-learning and lecture-based courses. These evaluations consisted of the interpretation of 10 different ECGs. RESULTS: We included 39 ED residents from four different hospitals. The precourse test showed that the overall average score of ECG interpretation was 40%. Nineteen participants were then assigned to the e-learning course and 20 to the lecture-based course. Globally, there was a significant improvement in ECG interpretation skills (accuracy score=55%, P=0.0002). However, this difference was not significant between the two groups (P=0.14). CONCLUSION: Our findings showed that the ECG interpretation was not optimal and that our e-learning program may be an effective tool for enhancing ECG interpretation skills among ED residents. A large European study should be carried out to evaluate ECG interpretation skills among ED residents before the implementation of ECG learning, including e-learning strategies, during ED residency.

Plasmatic presepsin (sCD14-ST) concentrations in acute pyelonephritis in adult patients.

INTRODUCTION: Presepsin (sCD14-ST) is an emerging biomarker for infection. We hypothesized that presepsin could specifically increase during acute pyelonephritis and correlate with severity. METHODS: We compared presepsin values in patients with acute pyelonephritis and controls, and we assessed its capacity to predict bacteraemia and admission in patients. RESULTS: In 312 patients with acute pyelonephritis (median age 33years), presepsin concentrations were higher than in controls (476 vs 200ng/L, p<0.001). ROC curve indicated an AUC at 0.90 [for presepsin (vs. 0.99 and 0.98 for CRP and PCT, respectively; p<0.05) and an optimal threshold at 340ng/L (74% sensitivity, 94% specificity). Presepsin concentrations increased in acute pyelonephritis patients with bacteraemia (614 vs. 461ng/L, p,=0.001) and in those requiring admission (614ng/L vs. 320ng/L, p<0.001). Performance of presepsin to predict bacteraemia [AUC=0.63, 95%CI: 0.55-0.72] was similar to CRP (AUC=0.64, p=0.87) and less accurate than PCT (AUC=0.78, p<0.001). AUC for presepsin to detect the need for admission was 0.67, and comparable to CRP (p=0.26) and PCT (p=0.18). CONCLUSION: Presepsin is a valuable biomarker to detect patients with acute pyelonephritis. However, it presents mild performance to predict bacteraemia and the need for admission, and offers no advantage as compared to CRP and PCT.

Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection.

BACKGROUND: Bacteremia, or bloodstream infection (BSI), is a leading cause of death among patients with certain types of cancer. A previous study reported that intestinal domination, defined as occupation of at least 30 % of the microbiota by a single bacterial taxon, is associated with BSI in patients undergoing allo-HSCT. However, the impact of the intestinal microbiome before treatment initiation on the risk of subsequent BSI remains unclear. Our objective was to characterize the fecal microbiome collected before treatment to identify microbes that predict the risk of BSI. METHODS: We sampled 28 patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic stem cell transplantation (HSCT) prior to administration of chemotherapy and characterized 16S ribosomal RNA genes using high-throughput DNA sequencing. We quantified bacterial taxa and used techniques from machine learning to identify microbial biomarkers that predicted subsequent BSI. RESULTS: We found that patients who developed subsequent BSI exhibited decreased overall diversity and decreased abundance of taxa including Barnesiellaceae, Coriobacteriaceae, Faecalibacterium, Christensenella, Dehalobacterium, Desulfovibrio, and Sutterella. Using machine-learning methods, we developed a BSI risk index capable of predicting BSI incidence with a sensitivity of 90 % at a specificity of 90 % based only on the pretreatment fecal microbiome. CONCLUSIONS: These results suggest that the gut microbiota can identify high-risk patients before HSCT and that manipulation of the gut microbiota for prevention of BSI in high-risk patients may be a useful direction for future research. This approach may inspire the development of similar microbiome-based diagnostic and prognostic models in other diseases.

MIC score, a new tool to compare bacterial susceptibility to antibiotics application to the comparison of susceptibility to different penems of clinical strains of Pseudomonas aeruginosa.

This study aimed to compare the susceptibility to carbapenems (imipenem, meropenem and doripenem) of clinical strains of Pseudomonas aeruginosa. It also studied whether susceptibility to imipenem or meropenem could predict, reliably, susceptibility to doripenem. Pseudomonal strains were collected from respiratory specimens, half of them from cystic fibrosis patients. MICs were determined according to European Committee on Antimicrobial Susceptibility Testing recommendations. Carbapenems were compared according to the susceptible, intermediate or resistant categories. A new approach also allowed comparing these carbapenems in a 'MIC score' taking into account the differences in breakpoints between drugs. One hundred thirty-nine strains were studied. They were found to be statistically more susceptible to meropenem than to the two other drugs. However, this difference was small: less than one dilution between the agents. This study also highlighted a significant correlation between susceptibility to penems taken in pairs. However, susceptibility to imipenem or meropenem did not reliably predict susceptibility to doripenem. Despite potential differences in resistance mechanisms, the Pseudomonas aeruginosa strains showed close susceptibility to three carbapenems. This was true for both cystic fibrosis patients and others. However, there were variations between strains. That justifies MICs to be determined for each of the three penems. This might be useful in case of elevated MICs and/or for potentially difficult-to-treat infections such as pneumonia in patients with cystic fibrosis patients.

e-Learning versus lecture-based courses in ECG interpretation for undergraduate medical students: a randomized noninferiority study.

OBJECTIVE: An ECG is pivotal for the diagnosis of coronary heart disease. Previous studies have reported deficiencies in ECG interpretation skills that have been responsible for misdiagnosis. However, the optimal way to acquire ECG interpretation skills is still under discussion. Thus, our objective was to compare the effectiveness of e-learning and lecture-based courses for learning ECG interpretation skills in a large randomized study. PARTICIPANTS AND METHODS: We conducted a prospective, randomized, controlled, noninferiority study. Participants were recruited from among fifth-year medical students and were assigned to the e-learning group or the lecture-based group using a computer-generated random allocation sequence. The e-learning and lecture-based groups were compared on a score of effectiveness, comparing the 95% unilateral confidence interval (95% UCI) of the score of effectiveness with the mean effectiveness in the lecture-based group, adjusted for a noninferiority margin. RESULTS: Ninety-eight students were enrolled. As compared with the lecture-based course, e-learning was noninferior with regard to the postcourse test score (15.1; 95% UCI 14.2; +∞), which can be compared with 12.5 [the mean effectiveness in the lecture-based group (15.0) minus the noninferiority margin (2.5)]. Furthermore, there was a significant increase in the test score points in both the e-learning and lecture-based groups during the study period (both P<0.0001). CONCLUSION: Our randomized study showed that the e-learning course is an effective tool for the acquisition of ECG interpretation skills by medical students. These preliminary results should be confirmed with further multicenter studies before the implementation of e-learning courses for learning ECG interpretation skills during medical school.

Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study.

INTRODUCTION: Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice. METHODS: Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed. RESULTS: One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15%. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model. CONCLUSIONS: We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality.

High variability among Emergency Departments in 3rd-generation cephalosporins and fluoroquinolones use for community-acquired pneumonia.

OBJECTIVE: Fluoroquinolones and 3rd-generation cephalosporins that are prescribed for pneumonia may be avoided and replaced by a penicillin in some cases. We aimed to determine if the proportion of patients treated for pneumonia with a cephalosporin, a fluoroquinolone or both varies among Emergency Departments (EDs), and to estimate the proportion of avoidable prescriptions. METHODS: This was a retrospective study of patients treated for pneumonia in eight French EDs, and subsequently hospitalized in non-ICU wards. Third-generation cephalosporins or respiratory fluoroquinolones were presumed unavoidable if they met both criteria: (1) age ≥65 years or comorbid condition; and (2) allergy or intolerance to penicillin, or failure of penicillin, or previous treatment with penicillin, or for fluoroquinolones only, suspected legionellosis. RESULTS: We included 832 patients. Thirty-four percent (95 % CI, 31-38 %) of patients were treated with a cephalosporin, a respiratory fluoroquinolone or both (range among EDs 19-44 %). Four EDs were independent risk factors for prescription of a cephalosporin, a fluoroquinolone or both [adjusted OR, 2.27 (1.64-3.15)], as were immune compromise [aOR 2.54 (1.56-4.14)], antibacterial therapy started before arrival in the ED [aOR 3.32 (2.30-4.81)], REA-ICU class III or IV [aOR 1.93 (1.15-3.23)], PSI class V [aOR 1.49 (1.00-2.20)], fluid resuscitation [aOR 3.98 (2.49-6.43)] and non-invasive ventilation in the ED [aOR, 7.18 (1.7-50.1)]. Treatment with a cephalosporin, a fluoroquinolone or both was avoidable in 67 % (62-73 %) of patients. CONCLUSION: Cephalosporins and fluoroquinolones use in pneumonia is highly variable among EDs. The majority of these prescriptions are avoidable. Antibiotic stewardship programs should be implemented to restrict their use in EDs.

Interest of repetitive transcranial magnetic stimulation of the motor cortex in the management of refractory cancer pain in palliative care: Two case reports.

BACKGROUND: Non-drug treatments should be systematically associated to the medical analgesic treatment during the terminal phase of cancer. CASES PRESENTATION: Patient 1, a 23-year-old woman, presented an adenocarcinoma of the rectum, with liver and lung metastases. Pain was initially treated by oral morphine and a combination of pregabalin and amitriptyline. Ketamine and intrathecal administration of morphine were both ineffective. Patient 2, a 69-year-old woman, presented a cutaneous T-cell lymphoma. She was admitted to the palliative care unit with mixed pain related to cutaneous lymphomatous infiltration. World Health Organization (WHO) step 3 analgesics had not been tolerated. CASES MANAGEMENT: Both patients received five consecutive 20-min sessions of repetitive transcranial magnetic stimulation to the right motor cortex. CASES OUTCOME: Patient 1 experienced a marked improvement of her pain over the days following the first repetitive transcranial magnetic stimulation session. Medical treatment was able to be rapidly decreased by about 50%, which restored an almost normal level of consciousness and lucidity. Patient 2's pain was also markedly decreased over the days following these five consecutive sessions, and repetitive transcranial magnetic stimulation also appeared to have had a beneficial effect on the patient's anxiety and mood. CONCLUSION: In the context of palliative care of cancer patients experiencing refractory pain that is difficult to control by the usual treatments, motor cortex repetitive transcranial magnetic stimulation, due to its noninvasive nature, can be used as an adjuvant therapy to improve various components of pain, including the emotional components. By reducing the doses of analgesics, repetitive transcranial magnetic stimulation decreases the severity of their adverse effects and improves the patient's quality of life.

The effect of work shift configurations on emergency medical dispatch center response.

OBJECTIVE: It has been proved that emergency medical dispatch centers (EMDC) save lives by promoting an appropriate allocation of emergency medical service resources. Indeed, optimal dispatcher call duration is pivotal to reduce the time gap between the time a call is placed and the delivery of medical care. However, little is known about the impact of work shift configurations (i.e., work shift duration and work shift rotation throughout the day) and dispatcher call duration. Thus, the objective of our study was to assess the effect of work shift configurations on dispatcher call duration. METHODS: During a 1-year study period, we analyzed the dispatcher call durations for medical and trauma calls during the 4 different work shift rotations (day, morning, evening, and night) and during the 10-hour work shift of each dispatcher in the EMDC of Nantes. We extracted dispatcher call durations from our advanced telephone system, configured with CC Pulse + (Genesys, Alcatel Lucent), and collected them in a custom designed database (Excel, Microsoft). Afterward, we analyzed these data using linear mixed effects models. RESULTS: During the study period, our EMDC received 408,077 calls. Globally, the mean dispatcher call duration was 107 ± 45 seconds. Based on multivariate linear mixed effects models, the dispatcher call duration was affected by night work shift and work shift duration greater than 8 hours, increasing it by about 10 ± 1 seconds and 4 ± 1 seconds, respectively (both p < 0.001). CONCLUSION: Our study showed that there was a statistically significant difference in dispatcher call duration over work shift rotation and duration, with longer durations seen over night shifts and shifts over 8 hours. While these differences are small and may not have clinical significance, they may have implications for EMDC efficiency.

In vivo efficacy of ceftolozane against Pseudomonas aeruginosa in a rabbit experimental model of pneumonia: comparison with ceftazidime, piperacillin/tazobactam and imipenem.

The aim of this study was to compare ceftolozane with ceftazidime, piperacillin/tazobactam (TZP) and imipenem in an experimental rabbit model of Pseudomonas aeruginosa pneumonia. Efficacy was assessed following 2 days of treatment by total colony counts in different tissues (lung, spleen and blood culture). Mean ± standard deviation pulmonary bacterial loads were 4.9 ± 0.3, 3.6 ± 0.3, 4.8 ± 0.2, 5.5 ± 0.8 and 3.9 ± 0.3 log10CFU/g of lung for ceftolozane (1g), ceftolozane (2g), ceftazidime, TZP and imipenem, respectively, compared with 6.3 ± 0.9 log10CFU/g of lung for control animals. The higher ceftolozane dose [2g three times daily (t.i.d.)] showed significantly better efficacy than the lower dose (1g t.i.d.). In conclusion, in this rabbit model of P. aeruginosa pneumonia, ceftolozane had an efficacy equivalent to that of comparator agents at a dose of 1g t.i.d. and had better efficacy at a higher dose (2g t.i.d.).