Changing needs of community-acquired pneumonia.
J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii3-iii9
Authors: Ramirez JA, Anzueto AR
Community-acquired pneumonia (CAP) is a serious condition associated with significan…

[Read more →]

Comparative ceftaroline activity tested against pathogens associated with community-acquired pneumonia: results from an international surveillance study.
J Antimicrob Chemother. 2011 Apr;66 Suppl 3:iii69-iii80
Authors: Jones R…

[Read more →]

Is cefepime safe for clinical use? A Bayesian viewpoint.
J Antimicrob Chemother. 2011 Apr 6;
Authors: Kalil AC
Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated …

[Read more →]

Ceftaroline pharmacodynamic activity versus community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus and vancomycin-resista…

[Read more →]

Correlation between antibiotic consumption and resistance of Gram-negative bacteria causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009.
J Antimicrob Chemother. 2011 Mar 24;
Authors: L…

[Read more →]

Early versus late oseltamivir treatment in severely ill patients with 2009 pandemic influenza A (H1N1): speed is life.
J Antimicrob Chemother. 2011 Mar 15;
Authors: Kumar A
The need for early antimicrobial therapy is w…

[Read more →]

Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia.
J Antimicrob Chemother. 2011 Mar 10;
Authors: Lu Q, Rouby JJ, Laterre PF,…

[Read more →]

Surviving the first hours in sepsis: getting the basics right (an intensivist’s perspective).
J Antimicrob Chemother. 2011 Apr;66 Suppl 2:ii11-ii23
Authors: Daniels R
Severe sepsis is a major cause of morbidity and mor…

[Read more →]

Antibiotic dosing in critical illness.
J Antimicrob Chemother. 2011 Apr;66 Suppl 2:ii25-ii31
Authors: McKenzie C
Early and effective antibiotic therapy is essential in the management of infection in critical illness. T…

[Read more →]

Diagnostic and prognostic biomarkers of sepsis in critical care.
J Antimicrob Chemother. 2011 Apr;66 Suppl 2:ii33-ii40
Authors: Kibe S, Adams K, Barlow G
Sepsis is a leading cause of mortality in critically ill patient…

[Read more →]

Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A.

J Antimicrob Chemother. 2011 Jan 7;

Authors: Rodríguez A, Díaz E, Martín-Loeches I, Sandiumenge A, Canadell L, Díaz JJ, Figueira JC, Marques A, Alvarez-Lerma F, Vallés J, Baladín B, García-López F, Suberviola B, Zaragoza R, Trefler S, Bonastre J, Blanquer J, Rello J,

Objectives The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A (2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between the timing of antiviral administration and intensive care unit (ICU) outcomes. Methods Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection. Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint. Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality. Results Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7?±?16.7 versus 18.4?±?14.2 days; P?=?0.03), hospital length of stay (34.0?±?20.3 versus 27.2?±?18.2 days; P?=?0.001) and MV days (17.4?±?15.2 versus 14.0?±?12.4; P?=?0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; OR?=?1.9; 95% CI 1.06-3.41). A multivariate model identified ET (OR?=?0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (OR?=?0.44; 95% CI 0.22-0.90; P?<?0.001). Conclusions Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.

PMID: 21385717 [PubMed - as supplied by publisher]

[Read more →]

Influence of fluoroquinolone consumption in inpatients and outpatients on ciprofloxacin-resistant Escherichia coli in a university hospital.

J Antimicrob Chemother. 2010 Dec;65(12):2650-7

Authors: Gallini A, Degris E, Desplas M, Bourrel R, Archambaud M, Montastruc JL, Lapeyre-Mestre M, Sommet A

The increase in fluoroquinolone-resistant Escherichia coli has raised the issue of treatment failure in common infections. Few studies have investigated the possible relationship between outpatient fluoroquinolone consumption and resistance in hospital.

PMID: 20876240 [PubMed - indexed for MEDLINE]

[Read more →]

Activity of moxifloxacin against intracellular community-acquired methicillin-resistant Staphylococcus aureus: comparison with clindamycin, linezolid and co-trimoxazole and attempt at defining an intracellular susceptibility breakpoint.

J Antimicrob Chemother. 2010 Dec 23;

Authors: Lemaire S, Kosowska-Shick K, Appelbaum PC, Glupczynski Y, Van Bambeke F, Tulkens PM

Background Co-trimoxazole, clindamycin and linezolid are used to treat community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, but little is known about intracellular activity. Moxifloxacin is active against intracellular methicillin-susceptible S. aureus (MSSA), but CA-MRSA has not been studied. Methods We used 12 clinical CA-MRSA, 1 MSSA overexpressing norA and 2 hospital-acquired MRSA (moxifloxacin MICs: 0.03 to 4 mg/L). Activity was assessed in broth and after phagocytosis by THP-1 macrophages or keratinocytes {concentration-dependent experiments [24 h of incubation] to determine relative potencies [EC(50)], static concentrations [C(s)] and maximal relative efficacies [E(max) (change in log(10) cfu compared with initial inoculum)] and time-dependent experiments [0-72 h] at human C(max)}. Results Concentration-dependent experiments: in broth, EC(50) and C(s) were correlated with the MIC for all antibiotics, but moxifloxacin achieved significantly (P?<?0.01) greater killing (more negative E(max)) than the comparators; and in THP-1 cells and keratinocytes, moxifloxacin acted more slowly but still reached a near bactericidal effect (2 to 3 log(10) cfu decrease) at 24 h with unchanged EC(50) and C(s) as long as its MIC was ?0.125 mg/L (recursive partitioning analysis). Clindamycin and linezolid were static, and co-trimoxazole was unable to suppress the intracellular growth of CA-MRSA. At human C(max) in broth, moxifloxacin killed more rapidly and more extensively (?5 log(10) cfu decrease at 10 h) than clindamycin (4 log(10) cfu at 48 h) or co-trimoxazole and linezolid (1-2 log(10) cfu at 72 h). Conclusions Moxifloxacin is active against both extracellular and intracellular CA-MRSA if the MIC is low, and is more effective than clindamycin, co-trimoxazole and linezolid.

PMID: 21186193 [PubMed - as supplied by publisher]

[Read more →]

Ceftaroline fosamil: a novel broad-spectrum cephalosporin with expanded anti-Gram-positive activity.

J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv9-16

Authors: Biek D, Critchley IA, Riccobene TA, Thye DA

Ceftaroline fosamil is a novel cephalosporin with broad-spectrum activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Streptococcus pneumoniae, and common Gram-negative organisms. The activity of ceftaroline against MRSA is attributed to its ability to bind to penicillin-binding protein (PBP) 2a with high affinity and inhibit the biochemical activity of PBP 2a more efficiently than other presently available ?-lactams. The activity of ceftaroline against MRSA and the ?-haemolytic streptococci makes it an attractive monotherapy agent for the treatment of complicated skin and skin structure infections (cSSSIs). Recent profiling and surveillance studies have shown that ceftaroline is active against contemporary skin pathogens collected from US and European medical centres in 2008. The mean free drug %T ?>? MIC (percentage of time the drug concentration remains above the MIC) needed for stasis ranged from 26% for S. aureus to 39% for S. pneumoniae in the murine thigh infection model. Pharmacokinetic and pharmacodynamic target attainment predictions for 600 mg of ceftaroline fosamil every 12 h showed that the mean %T? >? MICs for which plasma free-drug concentrations exceeded an MIC of 1 and 2 mg/L were 71% and 51% of the dosing interval, respectively. For a 40% T? > ?MIC target, the predicted attainments for infections due to pathogens for which ceftaroline MICs were 1 or 2 mg/L were 100% and 90%, respectively. Clinical and microbiological successes of ceftaroline fosamil in treating cSSSIs were demonstrated in two Phase III clinical studies, in which 96.8% of all baseline cSSSI isolates from the microbiologically evaluable population were inhibited by ceftaroline at ? 2 mg/L. Ceftaroline fosamil is a promising broad-spectrum agent for the treatment of cSSSIs.

PMID: 21115457 [PubMed - in process]

[Read more →]

Integrated safety summary of CANVAS 1 and 2 trials: Phase III, randomized, double-blind studies evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections.

J Antimicrob Chemother. 2010 Nov;65 Suppl 4:iv67-iv71

Authors: Corrado ML

OBJECTIVES: Treatment of complicated skin and skin structure infections (cSSSIs) requires therapy that is effective against a range of Gram-positive and Gram-negative bacteria, including resistant pathogens such as methicillin-resistant Staphylococcus aureus. Equally important is the need to provide therapy that is safe and well tolerated. Ceftaroline fosamil is a new-generation, parenteral cephalosporin that was developed for the treatment of moderate to severe bacterial infections, including cSSSIs. This report provides an integrated safety summary of the CeftAroliNe Versus VAncomycin in Skin and Skin Structure Infections (CANVAS) 1 and 2 studies (registration numbers NCT00424190 and NCT00423657). METHODS: Adult patients with cSSSIs requiring intravenous therapy received 600 mg of ceftaroline fosamil every 12 h or 1 g of vancomycin plus 1 g of aztreonam every 12 h for 5-14 days (randomized 1?:?1). All patients were followed for treatment-emergent adverse events (TEAEs) occurring from the start of the initial study drug infusion up to the test-of-cure visit, ?1 week following the last dose of study medication; serious adverse events (SAEs) that occurred within 30 days after the last dose were recorded. RESULTS: A total of 1378 patients received any amount of study drug and were included in the safety analysis. The percentage of patients with an SAE was similar between the ceftaroline fosamil and the vancomycin plus aztreonam groups (4.3% versus 4.1%). The majority of patients (>75%) had either no or mild TEAEs and the distribution of TEAEs based on severity was comparable between the groups. The most commonly reported TEAEs in patients treated with ceftaroline fosamil included nausea (5.9%), headache (5.2%), diarrhoea (4.9%) and pruritus (3.5%). CONCLUSIONS: Ceftaroline fosamil was well tolerated and did not result in any unexpected safety concerns. The data from the CANVAS trials suggest that ceftaroline fosamil has the expected safety and tolerability profile common to the cephalosporin class.

PMID: 21115456 [PubMed - in process]

[Read more →]