Archive for February, 2018

Pharmacokinetics, Safety, and Tolerability of Cefiderocol, a Novel Siderophore Cephalosporin for Gram-Negative Bacteria, in Healthy Subjects

Antimicrobial Agents & Chemotherapy March 2018 V.62 N.3 e02163-17

Yutaka Saisho, Takayuki Katsube, Scott White, Hiroyuki Fukase and Jingoro Shimada

Cefiderocol is a novel parenteral siderophore cephalosporin that shows potent efficacy against various Gram-negative bacteria, including carbapenem-resistant strains, in vitro and in preclinical models of infection.

The aim of the present study was to evaluate the pharmacokinetics (PK), safety, and tolerability of cefiderocol after both single and multiple dosing by intravenous infusion over 60 min in healthy adult subjects.

A single-ascending-dose study at doses of 100, 250, 500, 1,000, and 2,000 mg was conducted in 40 healthy Japanese males and females (6 individuals receiving the active drug and 2 individuals receiving a placebo per cohort).

A multiple-ascending-dose study at doses of 1,000 (two groups) and 2,000 mg every 8 h (q8h) was conducted in 30 healthy Japanese and Caucasian males (8 individuals receiving the active drug and 2 individuals receiving a placebo per cohort).

There were no serious or clinically significant adverse events (AEs) observed in either study. A single subject receiving 1,000 mg cefiderocol q8h was withdrawn due to AEs.

Dose-proportional increases in the maximum plasma concentration (Cmax), the area under the concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration after dosing, and the area under the concentration-time curve extrapolated from time zero to infinity were observed across the dose range of 100 to 2,000 mg.

The mean plasma half-life of cefiderocol was 1.98 to 2.74 h. Cefiderocol was primarily excreted unchanged in the urine (61.5% to 68.4% of the dose).

There was little accumulation of Cmax and AUC by dosing q8h, and the PK of cefiderocol did not change with multiple dosing. This study indicates that single and multiple intravenous doses of cefiderocol at up to 2,000 mg are well tolerated in healthy subjects and exhibit linear PK at doses up to 2,000 mg.



February 23, 2018 at 5:03 pm

A systems biology approach to the effect of aging, immunosenescence and vaccine response.

Current Opinion in Immunology August 2014 V.29 P.62-8.

Poland GA1, Ovsyannikova IG2, Kennedy RB2, Lambert ND2, Kirkland JL3.

Author information

1 Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA. Electronic address:

2 Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, USA.

3 Robert & Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.


Aging can lead to immunosenescence, which dramatically impairs the hosts’ ability to develop protective immune responses to vaccine antigens. Reasons for this are not well understood.

This topic’s importance is reflected in the increases in morbidity and mortality due to infectious diseases among elderly persons, a population growing in size globally, and the significantly lower adaptive immune responses generated to vaccines in this population.

Here, we endeavor to summarize the existing data on the genetic and immunologic correlates of immunosenescence with respect to vaccine response.

We cover how the application of systems biology can advance our understanding of vaccine immunosenescence, with a view toward how such information could lead to strategies to overcome the lower immunogenicity of vaccines in the elderly.


February 19, 2018 at 9:12 am

The microbiota and microbiome in aging: potential implications in health and age-related diseases.

J Am Geriatr Soc. April 2015 V.63 N.4 P.776-81.

Zapata HJ1, Quagliarello VJ.

Author information

1 Infectious Diseases Section, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut.


Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome).

Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina).

A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging.

Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation.

Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease.

Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.


February 19, 2018 at 9:11 am

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial

LANCET 17 February 2018 V.391 N.10.121 P.668-678

Prof Guy E Thwaites, FRCP, Matthew Scarborough, PhD, Alexander Szubert, MSc, Emmanuel Nsutebu, FRCP, Robert Tilley, MBChB, Julia Greig, FRCP, Sarah A Wyllie, FRCPath, Prof Peter Wilson, MD, Cressida Auckland, FRCPath, Janet Cairns, MSc, Denise Ward, BSc, Pankaj Lal, MD, Achyut Guleri, MD, Neil Jenkins, PhD, Julian Sutton, MD, Prof Martin Wiselka, FRCP, Gonzalez-Ruiz Armando, MD, Clive Graham, MD, Paul R Chadwick, FRCPath, Gavin Barlow, FRCP,


Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection.


In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants.


Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005).


Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia.


UK National Institute for Health Research Health Technology Assessment.





Rifampicin for Staphylococcus aureus bacteraemia: give it ARREST

Thomas L Holland, Vance G Fowler Jr

Although Staphylococcus aureus bacteraemia is both common and potentially lethal, clinical decisions involving its treatment remain largely unencumbered by high-quality data.1 With the ARREST multicentre, randomised, double-blind, placebo-controlled trial, Guy Thwaites and colleagues2 have contributed high-quality evidence and addressed an unresolved question involving the role of adjunctive rifampicin in treatment regimens for patients with S aureus bacteraemia….




February 18, 2018 at 10:48 pm

Clinical and epidemiological features of chronic Trypanosoma cruzi infection in patients with HIV/AIDS in Buenos Aires, Argentina

International Journal of Infectious Diseases February 2018 V.67 P.118–121

Andrés Guillermo Benchetrit, Marisa Fernández, Amadeo Javier Bava, Marcelo Corti, Norma Porteiro, Liliana Martínez Peralta


  • Chagas disease reactivation is an AIDS-defining illness with a high mortality rate.
  • Besides the vector-borne route, other means of T. cruzi infection acquisition must be assessed.
  • HIV-infected patients with lower CD4 T-cell counts are at higher risk of Chagas disease reactivation.
  • Severely immunecompromised patients infected with T. cruzi may have negative serological assay results.
  • Direct parasitological techniques should be performed in the diagnosis of patients for whom there is a suspicion of T. cruzi reactivation.


Trypanosoma cruzi reactivation in HIV patients is considered an opportunistic infection, usually with a fatal outcome. The aim of this study was to describe the epidemiological and clinical features of T. cruzi infection in HIV patients and to compare these findings between patients with and without Chagas disease reactivation.


The medical records of T. cruzi–HIV co-infected patients treated at the Muñiz Infectious Diseases Hospital from January 2005 to December 2014 were reviewed retrospectively. Epidemiological and clinical features were assessed and compared between patients with and without Chagas disease reactivation.


The medical records of 80 T. cruzi–HIV co-infected patients were reviewed. The most likely route of T. cruzi infection was vector-borne (32/80 patients), followed by intravenous drug use (12/80). Nine of 80 patients had reactivation. Patients without reactivation had a significantly higher CD4 T-cell count at diagnosis of T. cruzi infection (144 cells/μl vs. 30 cells/μl, p = 0.026). Chagas disease serology was negative in two of nine patients with reactivation.


Serological assays for T. cruzi infection may be negative in severely immunocompromised patients. Direct parasitological techniques should be performed in the diagnosis of patients for whom there is a suspicion of T. cruzi reactivation. HIV patients with a lower CD4 count are at higher risk of reactivation.



February 18, 2018 at 4:05 pm

Early-onset prosthetic valve endocarditis definition revisited: Prospective study and literature review

International Journal of Infectious Diseases February 2018 V.67 P.3–6

Rinaldo Focaccia Siciliano, Bruno Azevedo Randi, Danielle Menosi Gualandro, Roney Orismar Sampaio, Márcio Sommer Bittencourt, Christian Emmanuel da Silva Pelaes, Alfredo José Mansur, Pablo Maria Alberto Pomerantzeff, Flávio Tarasoutchi, Tânia Mara Varejão Strabelli


  • Studies reporting the etiology of prosthetic valve endocarditis (PVE) are an unmet clinical need.
  • A prospective cohort study was performed along with a literature review to describe the distribution of the etiology of PVE.
  • At >120 days after valve surgery, there is a decrease in the incidence of resistant microorganisms.
  • PVE occurring at >120 days after surgery may be treated with the same empirical treatment as for late PVE.
  • This approach could lead to higher antibiotic efficacy and less damage to the patient’s natural flora.


To determine the annual incidence of prosthetic valve endocarditis (PVE) and to evaluate its current classification based on the epidemiological distribution of agents identified and their sensitivity profiles.


Consecutive cases of PVE occurring within the first year of valve surgery during the period 1997–2014 were included in this prospective cohort study. Incidence, demographic, clinical, microbiological, and in-hospital mortality data of these PVE patients were recorded.


One hundred and seventy-two cases of PVE were included, and the global annual incidence of PVE was 1.7%. Most PVE cases occurred within 120 days after surgery (76.7%). After this period, there was a reduction in resistant microorganisms (64.4% vs. 32.3%, respectively; p = 0.007) and an increase in the incidence of Streptococcus spp (1.9% vs. 23.5%; p = 0.007). A literature review revealed 646 cases of PVE with an identified etiology, of which 264 (41%) were caused by coagulase-negative staphylococci and 43 (7%) by Streptococcus spp. This is in agreement with the current study findings.


Most PVE cases occurred within 120 days after valve surgery, and the same etiological agents were identified in this period. The current cut-off level of 365 days for the classification of early-onset PVE should be revisited.



February 18, 2018 at 4:03 pm

REVIEW – Environmental cleaning and disinfection of patient areas

International Journal of Infectious Diseases Ferbuary 2018 V.67 P.52–57

Michelle Doll, Michael Stevens, Gonzalo Bearman


The healthcare setting is predisposed to harbor potential pathogens, which in turn can pose a great risk to patients.

Routine cleaning of the patient environment is critical to reduce the risk of hospital-acquired infections.

While many approaches to environmental cleaning exist, manual cleaning supplemented with ongoing assessment and feedback may be the most feasible for healthcare facilities with limited resources.



February 10, 2018 at 9:18 am

Seroprevalence and risk factors of Hepatitis E infection in Jordan’s population: First report

International Journal of Infectious Diseases January 2018 V.66 P.121–125

Mohammad M. Obaidat, Amira A. Roess


  • Seroprevalce, risk factors and zoonotic potential of HEV were studied.
  • HEV antibodies occurs at high prevalence (30.9%) overall in Jordan.
  • HEV infection associates with age and eating undercooked meat.
  • Owning camels increased the odds of HEV seropositivity.


Hepatitis E virus (HEV) is hyperendemic in many countries, but data on this virus are not available in Jordan. This study determined the seroprevalence, risk factors and zoonotic potential of HEV in a Jordanian population.


A total of 450 sera samples from 8 different governorates were tested for HEV-IgG. A pre-tested and validated questionnaire was used to collect risk factor data including animal interaction and environmental exposures.


The overall seroprevalence was 30.9%. Eating undercooked meat was significantly associated with HEV seropositivity (OR = 2.06, 95%CI 1.04–4.06) after controlling for age, gender, travel history and source of water. Age was also associated with HEV seropositivity; the youngest (≤14 years of age) and oldest age groups (60 and 80 years of age) had the highest prevalence (45.5% and 53.2%, respectively), compared to those between 20 to 29 years of age and 30 to 39 years of age (20.2 and 15.2%, respectively), although the small sample size among the youngest group tempers this association. There was evidence of a marginal association between owning camels and an increased odds of HEV seropositivity. Place of residence and source of drinking water were not associated with infection.


This is the first study to report HEV seroprevalence in Jordan and shows that HEV exposure is high in Jordan. Surveillance for acute and chronic Hepatitis E is needed to estimate the frequency of the actual disease.



February 10, 2018 at 9:14 am

First case of New Delhi metallo-β-lactamase in Klebsiella pneumoniae from Ecuador: An update for South America

International Journal of Infectious Diseases December 2017 V.65 N. P.119–121

Daniel Romero-Alvarez, Jorge Reyes, Viviana Quezada, Carolina Satán, Nelson Cevallos, Sofía Barrera, Gabriel Trueba, Luis E. Escobar, José E. Villacís


  • The New Delhi metallo-β-lactamase (NDM) resistance plasmid has autochthonous circulation in Ecuador.
  • A Klebsiella pneumoniae ST147 harboring the NDM-1 gene in an IncA/C plasmid is described for the first time in Quito, Ecuador.
  • The circulation of NDM in South America has been addressed mainly by Brazil and Colombia.


To describe a clinical case of Klebsiella pneumoniae harboring a New Delhi metallo-β-lactamase (NDM) plasmid in Ecuador and to present a map of reports of NDM isolates in South America.


The modified Hodge test, carbapenem inactivation method, imipenem–EDTA disk method (synergy), and Rapidec Carba NP test were used to identify antibiotic resistance mechanisms. The presence of resistance genes was explored with a conjugation assay, and molecular confirmation of NDM was performed by PCR and DNA sequencing. Plasmid characterization was conducted by PCR-based replicon typing. A literature review was performed in Google Scholar and PubMed to identify reports from South America.


An HIV-infected patient, who had never traveled abroad, developed a bloodstream infection caused by K. pneumoniae ST147 harboring the NDM-1 resistance gene in a plasmid from the IncA/C group. Local circulation of NDM has also been described in other South American countries, in particular in Colombia and Brazil, although published scientific records were not found for other countries.


This report presents the first evidence of autochthonous circulation of the NDM-1 resistance gene harbored by an IncA/C plasmid isolated from a K. pneumoniae ST147 in Ecuador. Efforts should be implemented to monitor and characterize the spatial and temporal distribution of NDM in Ecuador and other countries of South America.



February 10, 2018 at 9:09 am

Adenovirus Type 4 Respiratory Infections among Civilian Adults, Northeastern United States, 2011–2015

Emerg Infect Dis. 2018 V.24 N.2 P.201-209

Adriana E. KajonComments to Author , Daryl M. Lamson, Camden R. Bair, Xiaoyan Lu, Marie L. Landry, Marilyn Menegus2, Dean D. Erdman, and Kirsten St. George

Author affiliations: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA (A.E. Kajon, C.R. Bair); New York State Department of Health, Albany, New York, USA (D.M. Lamson, K. St. George); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (X. Lu, D.D. Erdman); Yale University School of Medicine, New Haven, Connecticut, USA (M.L. Landry); University of Rochester Medical Center, Rochester, New York, USA (M. Menegus)


Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings. We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered from civilian adults with acute respiratory disease (ARD) in the northeastern United States during 2011–2015.

Specimens came from college students, residents of long-term care facilities or nursing homes, a cancer patient, and young adults without co-morbidities.

HAdV-4 genome types 4a1 and 4a2, the variants most frequently detected among US military recruits in basic training before the restoration of vaccination protocols, were isolated in most cases.

Two novel a-like variants were recovered from students enrolled at a college in Tompkins County, New York, USA, and a prototype-like variant distinguishable from the vaccine strain was isolated from an 18-year-old woman visiting a physician’s office in Ulster County, New York, USA, with symptoms of influenza-like illness. Our data suggest that HAdV-4 might be an underestimated causative agent of ARD among civilian adults.





February 9, 2018 at 6:47 pm

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