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Antibiotics in the clinical pipeline in 2011

wallyr — Sun, 22 May 2011 18:55:57 +0000

Butler MS et al. – The emergence of multi–drug–resistant bacteria and the lack of new antibiotics in the antibiotic drug development pipeline, especially those with new modes of action, is a major health concern.
Abstract
The emergence of multi-drug-resistant bacteria and the lack of new antibiotics in the antibiotic drug development pipeline, especially those with new modes of action, is a major health concern. This review lists the 20 new antibiotics launched since 2000 and records the 40 compounds currently in active clinical development. Compounds in the pipeline from new antibiotic classes are reviewed in detail with reference to their development status, mode of action, spectrum of activity and lead discovery. In addition, the NP or synthetic derivation is discussed, with activity against Gram-negative bacteria highlighted.

The Journal of Antibiotics , (18 May 2011) | doi:10.1038/ja.2011.44

Rising incidence of Staphylococcus aureus with reduced susceptibility to vancomycin and susceptibility to antibiotics: a global analysis 2004–2009

wallyr — Sun, 27 Feb 2011 05:56:03 +0000

Stephen P. Hawsera, , , Samuel K. Bouchillonb, Daryl J. Hobanb, Michael Dowzickyc and Tim Babinchakca
aIHMA Europe Sàrl, 4 Route de la Corniche, 1066 Epalinges, Switzerland
b International Health Management Associates, Schaumburg, IL, USA
c Pfizer, Inc., Collegeville, PA, USA
Received 30 September 2010; accepted 28 October 2010. Available online 15 January 2011.
Abstract
During 2004–2009, 20 004 isolates of Staphylococcus aureus were collected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Of these isolates, 8249 (41.2%) were meticillin-resistant S. aureus (MRSA) and 11 755 (58.8%) were meticillin-susceptible S. aureus (MSSA). A total of 4.0%, 5.3% and 3.0% of all S. aureus, MRSA and MSSA isolates, respectively, exhibited vancomycin minimum inhibitory concentrations (MICs) ≥2 μg/mL. Whilst no vancomycin-resistant S. aureus were encountered in this study and the majority of these isolates remained susceptible to vancomycin at the Clinical and Laboratory Standards (CLSI) breakpoint of 2 μg/mL, the total number of isolates with MICs creeping up to 2 μg/mL and above increased in all S. aureus from 4.0% in 2004 to 7.7% in 2009 (P < 0.001). Moreover, in MRSA this phenotype increased from 5.6% in 2004 to 11.1% in 2009 (P < 0.001). The increase was also notable for MSSA, which rose from 2.6% in 2004 to 5.6% in 2009 (P < 0.001). Of the 12 antibiotics tested, linezolid, minocycline, tigecycline and vancomycin were the most active agents by susceptibility against all S. aureus, all MRSA and all MSSA isolates. Against MRSA isolates with vancomycin MICs ≥ 2 μg/mL, susceptibility to vancomycin decreased from 100% in 2004 to 95.77% in 2009 (P > 0.05). Similarly, in MSSA isolates susceptibility to vancomycin decreased from 100% in 2004 to 91.07% in 2009 (P > 0.05). These data suggest that although the number of isolates of S. aureus with reduced susceptibility to vancomycin has increased significantly from 2004 to 2009, this upward creep of MICs has not yet impacted significantly on the overall susceptibility of vancomycin against either MRSA or MSSA.

International Journal of Antimicrobial Agents
Volume 37, Issue 3, March 2011, Pages 219-224

The Effect of Hospital-Acquired Clostridium difficile Infection on In-Hospital Mortality

wallyr — Sat, 04 Dec 2010 21:43:09 +0000

Oake N et al. – Hospital–acquired Clostridium difficile infection was independently associated with an increased risk of in–hospital death. Across all baseline risk strata, for every 10 patients acquiring the infection, 1 person died.Background The effects of hospital-acquired Clostridium difficile infection (CDI) on patient outcomes are incompletely understood. We conducted this study to determine the independent impact of hospital-acquired CDI on in-hospital mortality after adjusting for the time-varying nature of CDI and baseline mortality risk at hospital admission.

Methods This retrospective observational study used data from the Ottawa Hospital (Ottawa, Ontario, Canada) data warehouse. Inpatient admissions with a start date after July 1, 2002, and a discharge date before March 31, 2009, were included. Stratified analyses and a Cox multivariate proportional hazards regression model were used to determine if hospital-acquired CDI was associated with time to in-hospital death.

Results A total of 136 877 admissions were included. Hospital-acquired CDI was identified in 1393 admissions (overall risk per admission, 1.02%; 95% confidence interval [CI], 0.97%-1.06%). The risk of hospital-acquired CDI significantly increased as the baseline mortality risk increased: from 0.2% to 2.6% in the lowest to highest deciles of baseline risk. Hospital-acquired CDI significantly increased the absolute risk of in-hospital death across all deciles of baseline risk (pooled absolute increase, 11%; 95% CI, 9%-13%). Cox regression analysis revealed an average 3-fold increase in the hazard of death associated with hospital-acquired CDI (95% CI, 2.4-3.7); this hazard ratio decreased with increasing baseline mortality risk.

Conclusions Hospital-acquired CDI was independently associated with an increased risk of in-hospital death. Across all baseline risk strata, for every 10 patients acquiring the infection, 1 person died.
Background The effects of hospital-acquired Clostridium difficile infection (CDI) on patient outcomes are incompletely understood. We conducted this study to determine the independent impact of hospital-acquired CDI on in-hospital mortality after adjusting for the time-varying nature of CDI and baseline mortality risk at hospital admission.

Losing Touch in the Era of Superbugs

wallyr — Tue, 21 Sep 2010 21:19:58 +0000

Hass L – Nosocomial infections are increasingly multidrug resistant and at times more virulent. As such, they pose real threats to patients and clinicians. In this essay the author discusses his own methacillin–resistant staphylococcus infection and how it has affected his work in the hospital. In so doing, he reflects on the value of touch in the doctor–patient relationship. In particular, he discusses how gloves serve as a barrier to infection but also create a small distance between the doctors and their patients. The implications of contact precautions must be considered as we reflect on balancing patient–centered care with infection control.
Full Text Article:http://www.annfammed.org/cgi/content/full/8/5/461
Annals of Family Medicine 8:461-463 (2010)
© 2010 Annals of Family Medicine, Inc.
doi: 10.1370/afm.1164

Clostridium difficile PCR ribotype 027: assessing the risks of further worldwide spread

wallyr — Thu, 03 Jun 2010 18:04:59 +0000

Clements ACA et al. – This framework first requires identification of potential vehicles of introduction, including international transfers of hospital patients, international tourism and migration, and trade in livestock, associated commodities, and foodstuffs. It then calls for assessment of the risks of pathogen release, of exposure of individuals if release happens, and of resulting outbreaks. Health departments in countries unaffected by outbreaks should assess the risk of introduction or reintroduction of C difficile PCR ribotype 027 using a structured risk–assessment approach.
Highly virulent strains of Clostridium difficile have emerged since 2003, causing large outbreaks of severe, often fatal, colitis in North America and Europe. In 2008—10, virulent strains spread between continents, with the first reported cases of fluoroquinolone-resistant C difficile PCR ribotype 027 in three Asia-Pacific countries and Central America. We present a risk assessment framework for assessing risks of further worldwide spread of this pathogen. This framework first requires identification of potential vehicles of introduction, including international transfers of hospital patients, international tourism and migration, and trade in livestock, associated commodities, and foodstuffs. It then calls for assessment of the risks of pathogen release, of exposure of individuals if release happens, and of resulting outbreaks. Health departments in countries unaffected by outbreaks should assess the risk of introduction or reintroduction of C difficile PCR ribotype 027 using a structured risk-assessment approach.
The Lancet Infectious Diseases, Volume 10, Issue 6, Pages 395 – 404, June 2010

In Vitro Double and Triple Bactericidal Activities of Doripenem, Polymyxin B, and Rifampin against Multidrug-Resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli

wallyr — Wed, 26 May 2010 17:14:13 +0000

Urban C et al. – Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem–resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.
In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms
Antimicrobial Agents and Chemotherapy, June 2010, p. 2732-2734, Vol. 54, No. 6

Effectiveness of Alcohol-Based Hand Rubs for Removal of Clostridium difficile Spores from Hands

wallyr — Tue, 25 May 2010 18:49:27 +0000

Jabbar U et al. – Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.
Background.Alcohol‐based hand rubs (ABHRs) are an effective means of decreasing the transmission of bacterial pathogens. Alcohol is not effective against Clostridium difficile spores. We examined the retention of C. difficile spores on the hands of volunteers after ABHR use and the subsequent transfer of these spores through physical contact.

Methods.Nontoxigenic C. difficile spores were spread on the bare palms of 10 volunteers. Use of 3 ABHRs and chlorhexidine soap–and‐water washing were compared with plain water rubbing alone for removal of C. difficile spores. Palmar cultures were performed before and after hand decontamination by means of a plate stamping method. Transferability of C. difficile after application of ABHR was tested by having each volunteer shake hands with an uninoculated volunteer.

Results.Plain water rubbing reduced palmar culture counts by a mean (± standard deviation [SD]) of 1.57 ± 0.11 log10 colony‐forming units (CFU) per cm2, and this value was set as the zero point for the other products. Compared with water washing, chlorhexidine soap washing reduced spore counts by a mean (±SD) of 0.89 ± 0.34 log10 CFU per cm2; among the ABHRs, Isagel accounted for a reduction of 0.11 ± 0.20 log10 CFU per cm2 ( ), Endure for a reduction of 0.37 ± 0.42 log10 CFU per cm2 ( ), and Purell for a reduction of 0.14 ± 0.33 log10 CFU per cm2 ( ). There were no statistically significant differences between the reductions achieved by the ABHRs; only Endure had a reduction statistically different from that for water control rubbing ( ). After ABHR use, handshaking transferred a mean of 30% of the residual C. difficile spores to the hands of recipients.

Conclusions.Hand washing with soap and water is significantly more effective at removing C. difficile spores from the hands of volunteers than are ABHRs. Residual spores are readily transferred by a handshake after use of ABHR.
Infect Control Hosp Epidemiol 2010;31:565–570

Drug susceptibility and clonality of methicillin-resistant Staphylococcus epidermidis in hospitalized patients with hematological malignancies

wallyr — Mon, 03 May 2010 22:39:03 +0000

Nomura K et al. – The results represent two significant findings. One is the major capability of MRSE to colonize patients. The other is that some MRSE isolates proved to be sensitive to clindamycin, minocycline, and cephalosporin, so that using antibiotics to which MRSE is sensitive as first–line therapy can avoid the need for vancomycin in clinical settings.
Abstract
Purpose
To evaluate the clonal relatedness and drug susceptibility of Streptococcus epidermidis isolated from hematological patients.
Methods
All S. epidermidis isolated from hematological patients who developed bloodstream infections between June 2005 and December 2007 were included. The clonal relationship was tested by means of pulsed-field gel electrophoresis (PFGE) analysis.
Results
Fifteen methicillin-resistant S. epidermidis (MRSE) isolates were examined from patients’ blood culture samples. Two subgroups that differed approximately by 40% in their PFGE banding were identified. In clinical practice, two cases were cured with cephalosporin only, thus demonstrating sensitivity of the strains to beta-lactam antibiotics.
Conclusions
Our results represent two significant findings. One is the major capability of MRSE to colonize patients. The other is that some MRSE isolates proved to be sensitive to clindamycin, minocycline, and cephalosporin, so that using antibiotics to which MRSE is sensitive as first-line therapy can avoid the need for vancomycin in clinical settings.
Journal Irish Journal of Medical Science
Publisher Springer London
ISSN 0021-1265 (Print) 1863-4362 (Online)
Category Original Article
DOI 10.1007/s11845-010-0481-7
Subject Collection Medicine
SpringerLink Date Saturday, April 24, 2010

Contagious Period for Pandemic (H1N1) 2009

wallyr — Thu, 15 Apr 2010 02:44:30 +0000

De Serres G et al. – Human challenge studies with seasonal influenza have shown that virus shedding after day 7 is rare, but clinical studies have shown that shedding may persist beyond that period in some populations, such as elderly persons, immunocompromised patients, and children. In a study among hospitalized persons infected with seasonal influenza A viruses, 54% remained positive by PCR beyond 7 days after symptom onset, and 29% were positive by cell culture.
Emerging Infectious Diseases, 04/12/10 : Full Text Article available at the following link:
http://www.cdc.gov/eid/content/16/5/pdfs/09-1894.pdf

Surgical Masks for Protection of Health Care Personnel against Pandemic Novel Swine-Origin Influenza A (H1N1)- 2009: Results from an Observational Study

wallyr — Sun, 21 Mar 2010 20:45:06 +0000

Ang B et al. – There is ongoing debate about the efficacy of surgical masks versus N95 respirators for protection against pandemic novel swine–origin influenza A (H1N1)– 2009. The hospital, which is designated to manage outbreaks of emerging infection, has robust surveillance systems to detect infection in staff.

Breif Report: http://www.journals.uchicago.edu/doi/pdf/10.1086/651159
Clinical Infectious Diseases 2010;50:1011–1014