Archive for April, 2011

Comparative ceftaroline activity tested against pathogens associated with community-acquired pneumonia: results from an international surveillance study

Journal of Antimicrobial Chemotherapy April 2011 V.66  N.suppl 3

Ronald N. Jones*, David J. Farrell, Rodrigo E. Mendes and Helio S. Sader

JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA



To document the spectrum of activity of ceftaroline, the active form of the prodrug, ceftaroline fosamil, a new cephalosporin with anti-methicillin-resistant staphylococcal activity, against a surveillance collection of clinical isolates obtained from theUSAandEuropeduring 2008–09.


A selected group of species associated with community-acquired pneumonia (CAP; 6496 of 17 326 monitored strains) were tested for susceptibility in a central laboratory using CLSI broth microdilution methods. Organisms were sampled from 55 medical centres,27 intheUSAand 28 (12 countries) inEurope. Ceftaroline and comparator agents were tested and interpretations of MIC endpoints made by applying current CLSI (2010) and EUCAST (2010) breakpoint criteria.


Against 1340 Streptococcus pneumoniae, ceftaroline inhibited all isolates at ≤0.5 mg/L (MIC50/90, ≤0.008/0.12 mg/L) and was 8-fold more active than ceftriaxone (MIC90, 1 mg/L; only 79.2% coverage at EUCAST breakpoint). Haemophilus influenzae (n = 584; MIC50/90, ≤0.008/0.015 mg/L), Moraxella catarrhalis (n = 377; MIC50/90, 0.03–0.06/0.12 mg/L) and Staphylococcus aureus (n = 590; MIC50/90, 0.5/1 mg/L) were very susceptible to ceftaroline, regardless of β-lactamase production or multidrug resistance (MDR) patterns. The potency of ceftaroline against three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) was similar to that of ceftriaxone, ceftazidime and piperacillin/tazobactam. Only modest differences in rates of ceftaroline susceptibility (breakpoint ≤2 mg/L) were noted with extended-spectrum β-lactamase-negative Enterobacteriaceae strains between theUSAandEurope(97.9% versus 97.0% for E. coli). Ceftaroline, like ceftriaxone, was not active against ceftazidime-resistant E. coli (10.2%–26.2% susceptible at ≤2 mg/L) or K. pneumoniae (5.3%–11.2%).


The ceftaroline surveillance for 2008–09 (USAandEurope) documented low MIC50/90 values for S. aureus isolates at 0.5/1 and 0.25/1 mg/L, respectively. More importantly, ceftaroline MIC90 results for S. pneumoniae (0.12 mg/L), H. influenzae (0.015 mg/L) and M. catarrhalis (0.12 mg/L) were very low, all MICs being ≤0.5 mg/L. Ceftaroline exhibited promising high potency and wide coverage against Gram-positive and -negative pathogens known to cause CAP, especially isolates of MDR pneumococci and methicillin-resistant S. aureus.



April 23, 2011 at 3:48 pm Leave a comment

A Randomized Factorial Trial Comparing 4 Treatment Regimens in Treatment-Naive HIV-Infected Persons with AIDS and/or a CD4 Cell Count <200 Cells/µL in South Africa

Journal of Infectious Diseases 15 Nov  2010  V.202  N.10 P.1529-1537

The Phidisa II Writing Team for Project Phidisaa

Reprints or correspondence: Dr Michael A. Polis, NIAID/NIH, 6700B Rockledge Dr, Room 1118, Bethesda, MD 20892 (



Few randomized trials comparing antiretroviral therapy (ART) regimens have been conducted in resource-limited settings.


In the Republic of South Africa, antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals >14 years old with a CD4 cell count <200 cells/µL or a prior AIDS diagnosis were randomized to receive efavirenz (EFV) or lopinavir/ritonavir (LPV/r) with either zidovudine (ZDV) plus didanosine (ddI) or stavudine (d4T) plus lamivudine (3TC) in an open-label, 2-by-2 factorial study and followed up for the primary outcome of AIDS or death and prespecified secondary outcomes, including CD4 cell count and viral load changes, treatment discontinuation, and grade 4 events.


In total, 1771 persons were randomized and followed up for a median of 24.7 months. AIDS or death occurred in (1) 163 participants assigned EFV and 157 assigned LPV/r (hazard ratio [HR], 1.04 [95% confidence interval {CI}, 0.84–1.30]) and in (2) 170 participants assigned ZDV+ddI and 150 assigned d4T+3TC (HR, 1.15 [95% CI, 0.93–1.44]). HIV RNA levels were lower (P < .001) and CD4 cell counts were greater (P < .01) over follow-up for d4T+3TC versus ZDV+ddI. Rates of potentially life-threatening adverse events and overall treatment discontinuation were similar for d4T+3TC and ZDV+ddI; however, more participants discontinued d4T because of toxicity (12.6%) than other treatments (<5%).


EFV and LPV/r are effective components of first-line ART. The poorer viral and immune responses with ZDV+ddI and the greater toxicity-associated discontinuation rate with d4T+3TC suggest that these treatments be used cautiously as initial therapy.

Trial registration. identifier: NCT00342355.


April 23, 2011 at 3:46 pm Leave a comment

Antiretroviral Adherence and Development of Drug Resistance Are the Strongest Predictors of Genital HIV-1 Shedding among Women Initiating Treatment

Journal of Infectious Diseases 15 Nov  2010  V.202  N.10 P.1538-1542

Susan M. Graham1,3,5,7, Linnet Masese1,3, Ruth Gitau3, Zahra Jalalian-Lechak2, Barbra A. Richardson1, Norbert Peshu5, Kishor Mandaliya6, James N. Kiarie4, Walter Jaoko3, Jeckoniah Ndinya-Achola3, Julie Overbaugh2 and R. Scott McClelland1,3

1University of Washington, Seattle, Washington

2Fred Hutchinson Cancer Research Center, Seattle, Washington

3University of Nairobi, Nairobi, Kenya

4Kenyatta National Hospital, Nairobi, Kenya

5Kenya Medical Research Institute, Kilifi, Kenya

6Coast Provincial General Hospital, Mombasa, Kenya

7University of Toronto, Toronto, Ontario, Canada


Persistent genital human immunodeficiency virus type 1 (HIV-1) shedding among women receiving antiretroviral therapy (ART) may present a transmission risk. We investigated the associations between genital HIV-1 suppression after ART initiation and adherence, resistance, pretreatment CD4 cell count, and hormonal contraceptive use. First-line ART was initiated in 102 women. Plasma and genital HIV-1 RNA levels were measured at months 0, 3, and 6. Adherence was a strong and consistent predictor of genital HIV-1 suppression (P < .001), whereas genotypic resistance was associated with higher vaginal HIV-1 RNA level at month 6 (P = .04). These results emphasize the importance of adherence to optimize the potential benefits of ART for reducing HIV-1 transmission risk.


April 23, 2011 at 3:44 pm Leave a comment

Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria

Journal of Antimicrobial Chemotherapy  NOV.2010 V.65 N.Suppl.3  P.25-33

Ann Pallett1,* and Kieran Hand2

1Department of Microbiology, Southampton University Hospitals NHS Trust, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK

2Department of Pharmacy, Southampton University Hospitals NHS Trust, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK


Resistance in Gram-negative bacteria has been increasing, particularly over the last 6 years. This is mainly due to the spread of strains producing extended-spectrum β-lactamases (ESBLs) such as CTX-M enzymes or AmpC β-lactamases. Many of the isolates producing these enzymes are also resistant to trimethoprim, quinolones and aminoglycosides, often due to plasmid co-expression of other resistance mechanisms. CTX-M-producing Escherichia coli often occurs in the community and as E. coli is one of the commonest organisms causing urinary tract infections (UTIs) the choice of agents to treat these infections is diminishing. Novel combinations of antibiotics are being used in the community and broad-spectrum agents such as carbapenems are being used increasingly as empirical treatment for severe infections. Of particular concern therefore are reports in theUKof organisms that produce carbapenemases. As resistance is becoming more widespread, prudent use of antimicrobials is imperative and, as asymptomatic bacteriuria is typically benign in the elderly, antibiotics should not be prescribed without clinical signs of UTI. The use of antibiotics as suppressive therapy or long-term prophylaxis may no longer be defensible.



April 23, 2011 at 3:39 pm Leave a comment

Malaria Surveillance — United States, 2009

MMWR  April 22, 2011 V.60 N.SS-3  P.1-15

Sonja Mali, MPH, Kathrine R. Tan, MD, MPH, Paul M. Arguin, MD

Division of Parasitic Diseases and Malaria, Center for Global Health

Malaria, which is caused by the bite of an infected mosquito, is rare in theUnited States. Most cases in this country occur among persons who have travelled to areas outside of theU.S.with ongoing malaria transmission. This report presents malaria cases in persons in theUnited Statesin 2009….. 

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April 21, 2011 at 5:07 pm Leave a comment

Complicated skin and soft tissue infection

Journal of Antimicrobial Chemotherapy  NOV.2010 V.65 N.Suppl.3  P.35-44

Matthew S. Dryden*

Department of Microbiology, Royal Hampshire County Hospital, Romsey Road, Winchester SO22 5DG, UK


Skin and soft tissue infections (SSTIs) are common, and complicated SSTIs (cSSTIs) are the more extreme end of this clinical spectrum, encompassing a range of clinical presentations such as deep-seated infection, a requirement for surgical intervention, the presence of systemic signs of sepsis, the presence of complicating co-morbidities, accompanying neutropenia, accompanying ischaemia, tissue necrosis, burns and bites. Staphylococcus aureus is the commonest cause of SSTI across all continents, although its epidemiology in terms of causative strains and antibiotic susceptibility can no longer be predicted with accuracy. The epidemiology of community-acquired and healthcare-acquired strains is constantly shifting and this presents challenges in the choice of empirical antibiotic therapy. Toxin production, particularly with Panton–Valentine leucocidin, may complicate the presentation still further. Polymicrobial infection with Gram-positive and Gram-negative organisms and anaerobes may occur in infections approximating the rectum or genital tract and in diabetic foot infections and burns.

Successful management of cSSTI involves prompt recognition, timely surgical debridement or drainage, resuscitation if required and appropriate antibiotic therapy. The mainstays of treatment are the penicillins, cephalosporins, clindamycin and co-trimoxazole. β-Lactam/β-lactamase inhibitor combinations are indicated for polymicrobial infection. A range of new agents for the treatment of methicillin-resistant S. aureus infections have compared favourably with the glycopeptides and some have distinct pharmacokinetic advantages. These include linezolid, daptomycin and tigecycline. The latter and fluoroquinolones with enhanced anti-Gram-positive activity such as moxifloxacin are better suited for polymicrobial infection.



April 21, 2011 at 5:04 pm Leave a comment

Amikacin Monotherapy for Sepsis Caused by Panresistant Pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy 1 Nov. 2010 V.54 N.11 P.4939-4941

Brice Layeux, Fabio Silvio Taccone, David Fagnoul, Jean-Louis Vincent, and Frederique Jacobs

Department of Infectious Diseases, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium

Two patients with severe sepsis due to panresistant Pseudomonas aeruginosa, deteriorating despite therapy with colistin and β-lactams, were cured with a high daily dose (25 to 50 mg/kg) of amikacin to obtain a peak/MIC ratio of at least 8 to 10 (MIC = 16 µg/ml). Concomitant use of continuous venovenous hemodiafiltration (CVVHDF) provided no deterioration in renal function after treatment. High dosage of aminoglycosides combined with CVVHDF may represent a valuable therapeutic option for infection due to multiresistant pathogens.


April 21, 2011 at 5:02 pm Leave a comment

The diagnosis and management of prosthetic joint infections

Journal of Antimicrobial Chemotherapy  NOV.2010 V.65 N.Suppl.3  P.45-54

E. Moran1,2,*, I. Byren1,2 and B. L. Atkins1,2

1Department of Microbiology and Infectious Disease, John Radcliffe Hospital, Oxford OX3 9DU, UK

2Bone Infection Unit, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK


A host of technical and operative improvements have seen the rates of infection associated with joint replacement reach historic lows. However, the increasing number of operations being performed means that the absolute number of such infections remains significant. Diagnosis may be challenging and delaying appropriate treatment can lead to reduced joint function and the need for more complex, perhaps multiple, procedures. Individual centres tend to see small numbers of such cases, and in the absence of large clinical trials management varies. Early diagnosis, selection of an appropriate surgical strategy, accurate identification of the responsible microorganisms and construction of an appropriate antibiotic regimen are essential elements of any management strategy. Such packages of care are best delivered by a multidisciplinary team composed of orthopaedic and plastic surgeons, microbiologists, infectious disease physicians, specialist nurses, physiotherapists and occupational therapists. Each treatment plan must be developed in consultation with the patient, taking into account their aims and realistic goals. This review provides an overview of current understanding regarding diagnosis and treatment of prosthetic joint infections and suggests a treatment algorithm.



April 16, 2011 at 12:07 am Leave a comment

A CD4+ Cell Count <200 Cells per Cubic Millimeter at 2 Years After Initiation of Combination Antiretroviral Therapy Is Associated With Increased Mortality in HIV-Infected Individuals With Viral Suppression

JAIDS  Journal of Acquired Immune Deficiency Syndromes 1 Dec 2010  V.55  N.4  P.451-459

Clinical Science

Loutfy, Mona R; Genebat, Miguel; Moore, David; Raboud, Janet; Chan, Keith; Antoniou, Tony; Milan, David; Shen, Anya; Klein, Marina B; Cooper, Curtis; Machouf, Nima; Rourke, Sean B; Rachlis, Anita; Tsoukas, Chris; Montaner, Julio S G; Walmsley, Sharon L; Smieja, Marek; Bayoumi, Ahmed; Mills, Edward; Hogg, Robert S; and the CANOC Collaboration



To determine the long-term impact of immunologic discordance (viral load <50 copies/mL and CD4 count ≤200 cells/mm) in antiretroviral-naive patients initiating combination antiretroviral therapy (cART).


Our analysis included antiretroviral-naive individuals from a population-based Canadian Observational Cohort that initiated cART after January 1, 2000, and achieved virologic suppression. Multivariable Cox proportional hazards regression was used to examine the association between 1-year and 2-year immunologic discordance and time to death from all-causes. Correlates of immunologic discordance were assessed with logistic regression.


Immunologic discordance was observed in 19.9% (404 of 2028) and 10.2% (176 of 1721) of individuals at 1 and 2 years after cART initiation, respectively. Two-year immunologic discordance was associated with an increased risk of death [adjusted hazard ratio = 2.69; 95% confidence interval (CI): 1.26 to 5.78]. One-year immunologic discordance was not associated with death (adjusted hazard ratio = 1.12; 95% CI: 0.54 to 2.30). Two-year immunologic discordance was associated with older age (aOR per decade = 1.23; 95% CI: 1.03 to 1.48), male gender (aOR = 1.86; 95% CI: 1.09 to 3.16), injection drug use (aOR = 2.75; 95% CI: 1.81 to 4.17), and lower baseline CD4

count (aOR per 100 cells = 0.24; 95% CI: 0.19 to 0.31) and viral load (aOR per log copies/mL = 0.46; 95% CI: 0.33 to 0.65).


Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.


April 16, 2011 at 12:04 am Leave a comment

Human Rabies – Michigan, 2009

MMWR Weekly April 15, 2011  V.60  N.14 P.437-440


On November 9, 2009, aMichiganhospital informed CDC of suspected rabies in a man aged 55 years. The patient reportedly had awakened with a bat on his arm 9 months earlier but had not sought medical evaluation. He went to a local emergency department (ED) on October 30 and soon after was hospitalized; he died 12 days later. On November 14, CDC confirmed infection with a rabies virus variant that commonly infects the silver-haired bat (Lasionycteris noctivagans). This report summarizes the patient’s clinical course and the associated public health investigation. The report highlights the importance of public awareness of rabies, particularly among persons who might be at risk for wildlife exposures. Persons who experience contact with a bat and cannot confidently rule out a bite or scratch should seek prompt medical attention……

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April 16, 2011 at 12:02 am Leave a comment

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