Archive for July 8, 2018

Clinical response and mortality in tigecycline complicated intra-abdominal infection and complicated skin and soft-tissue infection trials

Internat J of Antimicrob Agents september 2015 V.46 N.3

Matteo Bassetti, Paul C. McGovern, Christoph Wenisch, R. Daniel Meyer, Jean Li Yan, Michele Wible, Scott T. Rottinghaus, Alvaro Quintana

Highlights

  • These analyses provide valuable insights into clinical response and mortality with tigecycline use.
  • These analyses suggest tigecycline is not a significant factor for clinical failure.
  • The cIAI analyses suggest tigecycline is not a significant factor for death.

An imbalance in all-cause mortality was noted in tigecycline phase 3 and 4 comparative clinical trials across all studied indications. We investigated clinical failure and mortality in phase 3 and 4 complicated skin and soft-tissue infection (cSSTI) and complicated intra-abdominal infection (cIAI) tigecycline trials using descriptive analyses of a blinded adjudication of mortality and multivariate regression analyses. Attributable mortality analyses of cSSTI revealed death due to infection in 0.1% of each treatment group (P = 1.000). In cIAI, there were no significant differences between tigecycline (1.2%) and comparator (0.7%) subjects who died due to infection (P = 0.243). For cIAI clinical failure, treatment interaction with organ dysfunction was observed with no difference observed between clinical cure for tigecycline (85.4%) and comparator (76.7%) treatment groups (odds ratio = 0.58, 95% confidence interval 0.28–1.19). Tigecycline-treated subjects had more adverse events of secondary pneumonias (2.1% vs. 1.2%) and more adverse events of secondary pneumonias with an outcome of death (0.5% vs. 0.1%). These analyses do not suggest that tigecycline is a factor either for failure (cSSTI and cIAI studies) or for death (cIAI studies).

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(15)00216-2/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(15)00216-2/pdf

Advertisements

July 8, 2018 at 5:55 pm

Forecasting carbapenem resistance from antimicrobial consumption surveillance: Lessons learnt from an OXA-48-producing Klebsiella pneumoniae outbreak in a West London renal unit

Internat J of Antimicrob Agents August 2015 V.46 N.2

Gharbi, L.S.P. Moore, M. Gilchrist, C.P. Thomas, K. Bamford, E.T. Brannigan, A.H. Holmes

Highlights

  • We forecast the incidence rate of carbapenem resistance using antimicrobial usage data.
  • We assess the impact of an antimicrobial stewardship intervention.
  • Meropenem usage was highly correlated with the incidence of OXA-48-producing organisms.
  • While meropenem usage decreased significantly, amikacin usage increased in the renal unit.

This study aimed to forecast the incidence rate of carbapenem resistance and to assess the impact of an antimicrobial stewardship intervention using routine antimicrobial consumption surveillance data. Following an outbreak of OXA-48-producing Klebsiella pneumoniae (January 2008–April 2010) in a renal cohort in London, a forecasting ARIMA model was derived using meropenem consumption data [defined daily dose per 100 occupied bed-days (DDD/100 OBD)] from 2005–2014 as a predictor of the incidence rate of OXA-48-producing organisms (number of new cases/year/100,000 OBD). Interrupted times series assessed the impact of meropenem consumption restriction as part of the outbreak control. Meropenem consumption at lag −1 year (the preceding year), highly correlated with the incidence of OXA-48-producing organisms (r = 0.71; P = 0.005), was included as a predictor within the forecasting model. The number of cases/100,000 OBD for 2014–2015 was estimated to be 4.96 (95% CI 2.53–7.39). Analysis of meropenem consumption pre- and post-intervention demonstrated an increase of 7.12 DDD/100 OBD/year (95% CI 2.97–11.27; P < 0.001) in the 4 years preceding the intervention, but a decrease thereafter. The change in slope was −9.11 DDD/100 OBD/year (95% CI −13.82 to −4.39). Analysis of alternative antimicrobials showed a significant increase in amikacin consumption post-intervention from 0.54 to 3.41 DDD/100 OBD/year (slope +0.72, 95% CI 0.29–1.15; P = 0.01). Total antimicrobials significantly decreased from 176.21 to 126.24 DDD/100 OBD/year (P = 0.05). Surveillance of routinely collected antimicrobial consumption data may provide a key warning indicator to anticipate increased incidence of carbapenem-resistant organisms. Further validation using real-time data is needed.

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(15)00149-1/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(15)00149-1/pdf

 

July 8, 2018 at 5:53 pm

Emergent and evolving antimicrobial resistance cassettes in community-associated fusidic acid and meticillin-resistant Staphylococcus aureus

Internat J of Antimicrob Agents May 2015 V.45 N.5

Matthew J. Ellington, Sandra Reuter, Simon R. Harris, Matthew T.G. Holden, Edward J. Cartwright, Daniel Greaves, Sarah M. Gerver, Russell Hope, Nicholas M. Brown, M. Estee Török, Julian Parkhill, Claudio U. Köser, Sharon J. Peacock

Highlights

  • Resistance to fusidic acid rose among meticillin-resistant Staphylococcus aureus (MRSA) during the 2000s.
  • Combined surveillance data and whole-genome sequencing analysis dissected changes in the epidemiology of MRSA.
  • Fusidic acid resistance emerged fastest in the community, where it was used the most.
  • Resistance occurred in diverse MRSA strains, encoded on staphylococcal cassette chromosome (SCC) elements.
  • Compact chimeric dual-resistance cassettes indicate a new mechanism for resistance accrual in MRSA.

Fusidic acid is a topical and systemic antimicrobial used for the treatment of staphylococcal infections in hospitals and the community. Sales of fusidic acid and resistance rates among meticillin-resistant Staphylococcus aureus (MRSA) doubled between 1990 and 2001. For the following decade, fusidic acid resistance rates among isolates from Addenbrooke’s Hospital (Cambridge, UK) were compared with national resistance rates from MRSA bacteraemia surveillance data and with antimicrobial sales data. Sales of fusidic acid remained relatively constant between 2002 and 2012, whilst fusidic acid resistance increased two- and four-fold in MRSA bacteraemias nationally and in MRSA isolates from Cambridge, respectively. A subgroup of MRSA resistant only to fusidic acid increased after 2006 by 5-fold amongst bacteraemias nationally and 17-fold (to 7.7% in 2012) amongst Cambridge MRSA isolates. All of the available local isolates from 2011 to 2012 (n = 23) were acquired in the community, were not related epidemiologically and belonged to multilocus sequence typing (MLST) groups ST1, 5, 8, 45 or 149 as revealed from analysis of whole-genome sequence data. All harboured the fusC gene on one of six distinct staphylococcal cassette chromosome (SCC) elements, four of which were dual-resistance chimeras that encoded β-lactam and fusidic acid resistance. In summary, fusidic acid-resistant MRSA increased in prevalence during the 2000s with notable rises after 2006. The development of chimeric cassettes that confer dual resistance to β-lactams and fusidic acid demonstrates that the genetics underpinning resistance in community-associated MRSA are evolving.

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(15)00064-3/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(15)00064-3/pdf

 

July 8, 2018 at 5:51 pm

β-Lactam antibiotics and vancomycin inhibit the growth of planktonic and biofilm Candida spp.: An additional benefit of antibiotic-lock therapy?

Internat J of Antimicrob Agents April 2015 V.45 N.4

José J.C. Sidrim, Carlos E.C. Teixeira, Rossana A. Cordeiro, Raimunda S.N. Brilhante, Débora S.C.M. Castelo-Branco, Silviane P. Bandeira, Lucas P. Alencar, Jonathas S. Oliveira, André J. Monteiro, José L.B. Moreira, Tereza J.P.G. Bandeira, Marcos F.G. Rocha

Highlights

  • β-Lactams and vancomycin reduced Candida biofilm formation.
  • β-Lactams and vancomycin inhibited the maintenance of mature Candida biofilms.
  • Antibiotic-lock therapy with these drugs might control Candida biofilm formation and maintenance.

The aim of this study was to evaluate the effects of cefepime, meropenem, piperacillin/tazobactam (TZP) and vancomycin on strains of Candida albicans and Candida tropicalis in planktonic and biofilm forms. Twenty azole-derivative-resistant strains of C. albicans (n = 10) and C. tropicalis (n = 10) were tested. The susceptibility of planktonic Candida spp. to the antibacterial agents was investigated by broth microdilution. The XTT reduction assay was performed to evaluate the viability of growing and mature biofilms following exposure to these drugs. Minimum inhibitory concentrations (MICs) ranged from 0.5 mg/mL to 2 mg/mL for cefepime, TZP and vancomycin and from 0.5 mg/mL to 1 mg/mL for meropenem and the drugs also caused statistically significant reductions in biofilm cellular activity both in growing and mature biofilm. Since all of the tested drugs are commonly used in patients with hospital-acquired infections and in those with catheter-related infections under antibiotic-lock therapy, it may be possible to obtain an additional benefit from antibiotic-lock therapy with these drugs, namely the control of Candida biofilm formation.

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(15)00006-0/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(15)00006-0/pdf

July 8, 2018 at 5:50 pm

A thorough QT study with dalbavancin: A novel lipoglycopeptide antibiotic for the treatment of acute bacterial skin and skin-structure infections

Internat J of Antimicrob Agents April 2015 V.45 N.4

Michael W. Dunne, Meijian Zhou, Borje Darpo

Highlights

  • A well designed and executed thorough QT study was performed.
  • Dalbavancin did not have an effect on the QTcF interval, and an effect exceeding 10 ms could be excluded at all time points after a single intravenous dose of 1000 mg and 1500 mg.
  • Dalbavancin did not exert a relevant effect on heart rate or on PR and QRS intervals.
  • A single 1500 mg dose of dalbavancin was well tolerated and displayed dose-proportional pharmacokinetics.

Two hundred healthy subjects were enrolled in a randomised, partially double-blinded, single-centre, parallel design thorough QT study to demonstrate that dalbavancin had no clinical effect on the 12-lead ECG QTc. Fifty patients in each group received either dalbavancin 1000 mg intravenous (i.v.), dalbavancin 1500 mg i.v. or placebo i.v., each infused over 30 min, or 400 mg oral moxifloxacin. Ten replicate 12-lead ECGs were extracted at pre-defined time points before and up to 24 h post dosing and at corresponding time points during baseline. Dalbavancin did not have an effect on the QTcF interval, and an effect exceeding 10 ms could be excluded at all time points after a single i.v. dose of 1000 mg and 1500 mg. The largest placebo-corrected change-from-baseline QTcF (ΔΔQTcF) was 1.5 ms in the 1000 mg dalbavancin group at 6 h and 0.2 ms in the 1500 mg group at 24 h. A small concentration-dependent effect of dalbavancin on ΔΔQTcF was identified with an estimated negative population slope of −0.0051 ms per μg/mL. Assay sensitivity was demonstrated by the effect of 400 mg moxifloxacin, which peaked at 2 h at ΔΔQTcF of 12.9 ms, with the lower bound of the 90% CI of the effect exceeding 5 ms at all three pre-defined time points. Dalbavancin did not exert a relevant effect on heart rate or PR or QRS intervals. Dalbavancin in i.v. doses up to 1500 mg did not prolong the QTc interval and had no effect on heart rate or PR and QRS intervals.

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(15)00030-8/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(15)00030-8/pdf

July 8, 2018 at 5:47 pm

REVIEW – Inhaled antibiotics beyond aminoglycosides, polymyxins and aztreonam: A systematic review

Internat J of Antimicrob Agents March 2015 V.45 N.3

Matthew E. Falagas, Kyriakos K. Trigkidis, Konstantinos Z. Vardakas

Highlights

  • Evaluation of published evidence regarding uncommon inhaled antibiotics.
  • Clinical and microbiological outcomes.
  • Future prospects.

We sought to evaluate published evidence regarding clinical or microbiological outcomes related to the use of inhaled antibiotics other than aminoglycosides, polymyxins and aztreonam. A systematic search of PubMed and Scopus databases as well as bibliographies of eligible articles was performed. In total, 34 eligible studies were identified. Among several inhaled β-lactams, ceftazidime was used with varying success in the prevention and treatment of ventilator-associated pneumonia (VAP) and improved clinical outcomes in chronic Pseudomonas aeruginosa lower respiratory tract infections (LRTIs) in patients with cystic fibrosis (CF) or bronchiectasis. Inhaled vancomycin, as an adjunctive therapy, was effective in treating Gram-positive VAP, whilst inhaled levofloxacin, ciprofloxacin and an inhaled combination of fosfomycin and tobramycin were associated with improved microbiological or clinical outcomes in chronic LRTI in patients with CF or bronchiectasis. In conclusion, published evidence is heterogeneous with regard to antibiotics used, studied indications, patient populations and study designs. Therefore, although the currently available data are encouraging, no safe conclusion regarding the effectiveness and safety of the drugs in question can be reached.

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(14)00329-X/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(14)00329-X/pdf

July 8, 2018 at 5:46 pm

REVIEW – The clinical positioning of telavancin in Europe

Internat J of Antimicrob Agents March 2015 V.45 N.3

Robert Masterton, Giuseppe Cornaglia, Patrice Courvalin, Hartmut M. Lode, Jordi Rello, Antoni Torres

Highlights

  • Clinical experience with the lipoglycopeptide telavancin in Europe is limited.
  • Telavancin has potent in vitro activity against Gram-positive isolates, e.g. meticillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA).
  • Telavancin is non-inferior to vancomycin for nosocomial Gram-positive pneumonia.
  • Baseline moderate-to-severe renal impairment increases mortality risk of telavancin.
  • Where renal function permits, telavancin is an alternative to vancomycin or linezolid.

Telavancin was the first marketed lipoglycopeptide. Although licensed in Europe in 2011 for the treatment of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus (MRSA), it did not become clinically available until March 2014. Given the limited clinical experience with telavancin in Europe, this review provides an overview of its antimicrobial and clinical activity as well as its position among today’s antimicrobials, with particular focus on the implications of its licensing requirements. Telavancin has potent in vitro activity against isolates of Gram-positive pathogens, including MRSA and glycopeptide-intermediate S. aureus strains. In addition, at clinically attainable doses telavancin inhibits Gram-positive isolates of antibiotic-resistant strains from biofilm models. The in vitro potency of telavancin has been corroborated in the clinical setting. Comparative clinical studies of telavancin demonstrate non-inferiority compared with vancomycin in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for telavancin-treated patients with monomicrobial S. aureus infection, including isolates with reduced vancomycin susceptibility. These studies also demonstrate an overall similar safety profile for telavancin and vancomycin, although importantly, patients with moderate-to-severe renal impairment at baseline are at greater risk for mortality with telavancin and this feature must be taken into account when selecting patients for its usage. In Europe, telavancin is a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. For example, it should be considered in such patients when vancomycin and linezolid are not suitable and where renal function permits.

FULL TEXT

https://www.ijaaonline.com/article/S0924-8579(14)00384-7/fulltext

PDF

https://www.ijaaonline.com/article/S0924-8579(14)00384-7/pdf

July 8, 2018 at 5:44 pm

Older Posts


Calendar

July 2018
M T W T F S S
« Jun   Aug »
 1
2345678
9101112131415
16171819202122
23242526272829
3031  

Posts by Month

Posts by Category