Archive for January, 2016

Zika Virus Spreads to New Areas — Region of the Americas, May 2015–January 2016

MMWR Morb Mortal Wkly Rep 2016;65:56–9

Morgan Hennessey, DVM; Marc Fischer, MD; J. Erin Staples, MD, PhD.




January 30, 2016 at 10:44 am

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis

Antimicrobial Agents and Chemotherapy December 2015 V.59 N.12 P.7224-7231

Tihana Bicanic, Christian Bottomley, Angela Loyse, Annemarie E. Brouwer, Conrad Muzoora, Kabanda Taseera, Arthur Jackson, Jacob Phulusa, Mina C. Hosseinipour, Charles van der Horst, Direk Limmathurotsakul, Nicholas J. White, Douglas Wilson, Robin Wood, Graeme Meintjes, Thomas S. Harrison, and Joseph N. Jarvis

aInstitute of Infection and Immunity, St. George’s University of London, London, United Kingdom

bFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom

cElisabeth Hospital, Tilburg, the Netherlands

dMbarara University of Science and Technology, Mbarara, Uganda

eUniversity of North Carolina Project, Lilongwe, Malawi

fMahidol-Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

gCentre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom

hEdendale Hospital, Pietermaritzburg, South Africa

iDesmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

jDivision of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

kInstitute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

lDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom

mBotswana-UPenn Partnership, Gaborone, Botswana

nDivision of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia.

Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied.

Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome.

In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days.

Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely.

The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality.

In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect.

The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.



January 30, 2016 at 8:48 am

Tedizolid Population Pharmacokinetics, Exposure Response, and Target Attainment

Antimicrobial Agents and Chemotherapy November 2014 V.58 N.11 P.6462-6470

Flanagan, J. Passarell, Q. Lu, J. Fiedler-Kelly, E. Ludwig, and P. Prokocimer

aCubist, San Diego, California, USA

bCognigen Corporation, Buffalo, New York, USA

Tedizolid phosphate is a novel antibacterial prodrug that is rapidly and extensively converted to its active moiety, tedizolid. We developed a population pharmacokinetics (PK) model for tedizolid using pooled data from seven densely and sparsely sampled clinical trials evaluating oral and intravenous tedizolid.

Model-derived exposure estimates were evaluated for relationships to select efficacy and safety outcomes. A two-compartment model with sigmoidal absorption, absolute bioavailability, and linear elimination described the PK data well.

Variability was small (clearance, 31% coefficient of variation; volume, 13.4% coefficient of variation), and absolute bioavailability was high (86%). No clinically significant covariate effects on tedizolid PK were found.

Based on phase 3 data evaluating 200-mg once-daily tedizolid for acute bacterial skin and skin structure infections (ABSSSI), no relationships were seen between various efficacy outcomes and estimated tedizolid exposure; the estimated exposure range (free-drug area under the concentration-time curve over 24 h at steady state [AUCss(0–24)], 7 to 50 μg · h/ml) in these patients was modest.

Safety data modeling, using once-daily doses of up to 400 mg, showed a small increase in the probability of an adverse event with increasing model-estimated tedizolid exposure; no such relationship was observed when specifically evaluating the 200-mg dose.

There were no trends in neutrophil or platelet counts with increasing tedizolid exposure.

Target attainment simulations for 200-mg tedizolid indicated a 98.31% probability of attaining the target measure (AUC for the free, unbound fraction of a drug [fAUC]/MIC = 3) against a Staphylococcus aureus strain for which the MIC was ≤0.5 μg/ml.

These findings support 200-mg tedizolid once daily as the optimum dose for treatment of ABSSSI.



January 30, 2016 at 8:46 am

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

Antimicrobial Agents and Chemotherapy November 2015 V.58 N.11 P.6471-6476

Flanagan, S. L. Minassian, D. Morris, R. Ponnuraj, T. C. Marbury, H. W. Alcorn, E. Fang, and P. Prokocimer

aCubist, San Diego, California, USA

bMinassian Biostatistics, Inc., San Diego, California, USA

cCovance, Madison, Wisconsin, USA

dOrlando Clinical Research Center, Orlando, Florida, USA

eDaVita Clinical Research, Minneapolis, Minnesota, USA

Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects.

Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function.

Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis.

Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function.

Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion.

The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (∼8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (∼9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis.

Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group.

Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment.

(This study has been registered at under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].)


January 30, 2016 at 8:43 am

Telavancin for Hospital-Acquired Pneumonia: Clinical Response and 28-Day Survival

Antimicrobial Agents and Chemotherapy April 2014 V.59 N.4 P.2030-2037

Ralph Corey, Marin H. Kollef, Andrew F. Shorr, Ethan Rubinstein, Martin E. Stryjewski, Alan Hopkins, and Steven L. Barriere

aDepartment of Medicine, Duke Clinical Research Institute, Durham, North Carolina, USA

bPulmonary and Critical Care Division, Washington University School of Medicine, St. Louis, Missouri, USA

cPulmonary and Critical Care Medicine, Washington Hospital Center, Washington, DC, USA

dUniversity of Manitoba, Winnipeg, Manitoba, Canada

eDepartment of Medicine, Section of Infectious Diseases, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno, Buenos Aires, Argentina

fTheravance, Inc., South San Francisco, California, USA

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality.

The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively).

The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups.

Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CLCR] of <50 ml/min).

Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available.


January 30, 2016 at 8:40 am

Brote de Encefalitis de San Luis en el área metropolitana Buenos Aires

Medicina Junio 2011 V.71 N.3

Alfredo Seijo1, Alejandra Morales2, Gladys Poustis1, Yamila Romer1, Ernesto Efron3, Guillermo Vilora4, Susana Lloveras1, Sergio Giamperetti1, Teresita Puente5, Jessica Monroig1, Victoria Luppo2, Delia Enria2

1Hospital de Enfermedades Infecciosas Francisco J. Muñiz,

2Instituto Nacional de Enfermedades Virales Humanas, J. Maiztegui, Pergamino,

3Hospital Británico,

4Hospital Ramos Mejía,

5Sanatorio Julio Méndez, Buenos Aires


Se describen los hallazgos epidemiológicos y clínicos de 13 enfermos con diagnóstico de infección por virus de la encefalitis de San Luis, con transmisión entre enero y marzo de 2010, en el Area Metropolitana Buenos Aires (AMBA).

Los 13 enfermos, promedio de edad 38 años, tuvieron un comienzo agudo caracterizado por hipertermia y cefalea.

Entre los días dos y diez de iniciados los síntomas, 7/13 enfermos tuvieron signos y síntomas de compromiso neurológico caracterizado por meningitis sin signos encefálicos en 1/7.

En 6/7 los hallazgos más frecuentes fueron: rigidez de nuca, desorientación temporoespacial, fotofobia, confusión y alteración del lenguaje.

Dos resonancias magnéticas y un electroencefalograma presentaron signos de afectación de lóbulos temporales.

El líquido cefalorraquídeo se caracterizó por pleocitosis con predominio de células mononucleadas, glucorraquia normal y discreto aumento de proteínas. No hubo casos fatales. En 6/13 pacientes la sospecha clínica inicial fue dengue.

Por la agrupación espacial y temporal de los casos puede considerarse un brote epidémico, el primero conocido en el AMBA, ya que no se había notificado previamente la circulación epidémica del virus.


January 29, 2016 at 2:48 pm

Pneumococcal empyema and complicated pneumonias: global trends in incidence, prevalence, and serotype epidemiology

European J of Clinical Microb & Infec Dis June 2014 V.33 N.6 P.879-910

  1. A. Fletcher , H.-J., M. Syrochkina, G. Sylvester
  2. Pfizer, Inc., 23–25, avenue du Dr Lannelongue, 75668, Paris Cedex 14, France
  3. Pfizer, Inc., Yekaterinburg, Russia
  4. Pfizer Inc., Collegeville, PA, USA


This review evaluates the serotype epidemiology of complicated pneumococcal pneumonia (CPP) during the period 1990–2012. PubMed and EMBASE were searched using the terms “empyema”, “complicated pneumonia”, “pleural infection”, “necrotizing pneumonia”, “pleural effusion”, “parapneumonic effusion”, “pneumatocele”, or “lung abscess”; “pneumococcal” or “Streptococcus pneumoniae”; and “serotype” for studies on the epidemiology of complicated pneumonias published from January 1, 1990 to October 1, 2013.

Studies with data on incidence and serotypes were included; reviews, case reports, and conference abstracts were excluded. Of 152 papers, 84 fitted the inclusion criteria.

A few pneumococcal serotypes were predominant causes of CPP, particularly serotypes 1, 19A, 3, 14, and 7F. CPP was a more common manifestation of pneumococcal disease among older (>2 years old) than younger children.

The data support increases in both reported incidence rates and proportions of CPP in children and adults during the period 1990–2012; specific increases varied by geographic region.

The proportions of serotype 3 and, particularly in Asia, serotype 19A CPP have increased, whereas most studies show declines in serotype 14. Serotype 1 has been a predominant cause of CPP since 1990, while antibiotic resistance was infrequent among serotype 1 isolates.

The reported incidence and proportions of CPP among pneumonia cases steadily increased from 1990 to 2012. Several factors might account for these increases, including enhanced disease detection due to a higher index of suspicion, more sophisticated diagnostic assays, and changes in the prevalence of serotypes with capacity to invade the pleural space that were not targeted by the 7-valent pneumococcal conjugate vaccine (PCV7).



January 29, 2016 at 7:54 am

CMV in the gut: a critical review of CMV detection in the immunocompetent host with colitis

European J of Clinical Microb & Infec Dis January 2015 V.34 N.1 P.13-18

  1. L. Goodman , C. D. Murray, J. Watkins, P. D. Griffiths, D. P. Webster
  2. Department of Infection and Immunity, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK
  3. Department of Gastroenterology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK
  4. Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, NW3 2QG, UK
  5. Centre for Virology, University College London Medical School, Rowland Hill Street, London, NW3 2PF, UK


As scientific techniques for the detection of cytomegalovirus (CMV) improve, we are able to detect small amounts of CMV in the mucosal wall. As clinicians, we are unsure how to interpret the results of this novel test. There is controversy in the literature as to the significance of the detection of CMV in the gut. Whilst the importance of CMV and reactivation of the virus is clear in those patients such as allograft recipients with established immune compromise, the role is less clear in patients with less damaged immune systems. We explore whether the detection of CMV in such cases influences outcome and how it should be optimally managed. We discuss the optimal management of such cases, according to current guidelines, with a review of the literature.



January 28, 2016 at 2:33 pm

Epidemiology, clinical history and microbiology of peritonsillar abscess

European J of Clinical Microb & Infec Dis March 2015 V.34 N.3 P.549-554

Mazur , E. CzerwińskaAffiliated, I. Korona-Głowniak, A. Grochowalska, M. Kozioł-Montewka

Medical Microbiology Department, Medical University of Lublin, ul. Chodźki 1, 20-093, Lublin, Poland

Department of Otolaryngology, Regional Specialist Hospital in Radom, ul. Aleksandrowicza 5, 26-617, Radom, Poland

Department of Pharmaceutical Microbiology, Medical University of Lublin, ul. Chodźki 1, 20-093, Lublin, Poland

Microbiological Laboratory, Regional Specialist Hospital in Radom, ul. Aleksandrowicza 5, 26-617, Radom, Poland


The purpose of this investigation was to explore the epidemiology, clinical history and microbiology of peritonsillar abscess (PTA). A retrospective review of PTA cases treated at the Department of Otolaryngology, Regional Specialist Hospital in Radom, Poland between 1st October 2003 and 30th September 2013 was undertaken. A total of 111 PTA patients were admitted. The study population consisted of 57.7 % males and 42.3 % females, with an average age of 31.0 (range 5–78) years. Smokers comprised 22.0 % of the study group. The seasonal variation of PTA was statistically insignificant (p = 0.45). Recurrent tonsillitis occurred in 35.5 % of patients. In comparison with the rest of the study population, patients with a history of recurrent pharyngotonsillitis had higher incidence of previous PTA episodes [odds ratio (OR) 17.8, 95 % confidence interval (CI) 2.1–148.7, p = 0.001]. Also, they were more frequently treated with antibiotics prior to hospitalisation (OR 4.6, 95 % CI 2.0–10.9, p = 0.0005) and had significantly longer hospital stay (p = 0.03). Bacterial cultures of abscess aspirates were performed in 40.5 % of patients. Monomicrobial growth was detected in 77.8 % of aerobic cultures. Streptococcus pyogenes, growing most frequently in monoculture, was found in 28.9 % of aerobic cultures. PTA patients with and without recurrent pharyngotonsillitis differed with regard to clinical history and course of disease. The percentage of smokers among PTA patients was lower than that described in the literature. Monomicrobial growth predominated in PTA aspirate cultures. S. pyogenes proved to be the most frequent pathogen.



January 28, 2016 at 2:32 pm

Empirical antibiotic therapy for pneumonia in intensive care units: a multicentre, retrospective analysis of potentially pathogenic microorganisms identified by endotracheal aspirates cultures

Europ J of Clinical Microb & Infec Dis Nov 2015 V.34 N.11 P.2295-2305

B. J. Scholte , H. L. Duong, C. Linssen, H. Van Dessel, D. Bergmans, R. van der Horst, P. Savelkoul

Department of Medical Microbiology, Maastricht University Medical Centre+

Zentrum für Intensivmedizin, Luzerner Kantonsspital, 6000, Luzern 16, Switzerland

Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands

Department of Medical Microbiology, Zuyderland Medical Centre, Heerlen, The Netherlands

Department of Medical Microbiology, Maastricht University Medical Centre+, Maastricht, The Netherlands

Department of Pulmonary Medicine and Intensive Care Medicine, Zuyderland Medical Centre, Heerlen, The Netherlands


The purpose of this investigation was to explore the presumed relationship between the days of hospitalisation and microorganisms identified by endotracheal aspirate cultures in relation to adequate empirical treatment strategies of pneumonia in the intensive care unit (ICU). All potentially pathogenic microorganisms identified by (surveillance) cultures of endotracheal aspirates obtained in the ICUs of two Dutch teaching hospitals in 2007 and 2012 were retrospectively collected and analysed. Antibiotic susceptibilities to 11 antibiotics were calculated for several time points (days or weeks) after hospital admission and expressed per patient-day. In total, 4184 potentially pathogenic microorganisms identified in 782 patients were analysed. Prevalence of the classic early-onset pneumonia-causing microorganisms decreased from 55 % on the first four days to 34 % on days 4–6 after hospital admission (p < 0.0001). Susceptibility to amoxicillin/clavulanic acid was below 70 % on all days. Except for days 0 and 12, susceptibility to ceftriaxone was below 80 %. The overall susceptibility to piperacillin/tazobactam was 1518/1973 (77 %) in 2007 vs. 727/1008 (67 %) in 2012 (p < 0.0001). After day 8 of hospital admission, susceptibility to piperacillin/tazobactam therapy was below 80 % in 2012. After one week of hospital admission, susceptibilities to antibiotics were lower in the hospital that included that antibiotic in the local empirical treatment protocols as compared to the hospitals in which that antibiotic was not or infrequently included: 90/434 (21 %) vs. 117/398 (29 %); p = 0.004 for amoxicillin/clavulanic acid and 203/433 (47 %) vs. 253/398 (64 %); p < 0.001 for ceftriaxone. No cut-off in the number of days after hospital admission could be identified to distinguish early-onset from late-onset pneumonia. Consequently, the choice of empirical antibiotics should probably not be based on the time of onset.




January 28, 2016 at 2:30 pm

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