IDSA News - March 2012
(Print All Articles)

EIN Update: A Complex Case of Multidrug Resistant P. aeruginosa

The Emerging Infections Network (EIN) is a forum for infectious diseases consultants and public health officials to report information on clinical phenomena and epidemiological issues with public health significance. Any diagnostic or therapeutic recommendations and all opinions presented are those of the individual contributor. They do not necessarily represent the views of EIN, IDSA (EIN’s sponsor), or the Centers for Disease Control and Prevention (CDC), which funds EIN. The reader assumes all risks in using this information.

EIN members recently discussed a complex case of multidrug-resistant Pseudomonas aeruginosa, highlighting the need for new antimicrobials to treat serious resistant infections.

“I'm currently taking care of a 23-year-old white female who was originally admitted to an outside hospital with complaints of fever, cough, and hemoptysis,” an EIN member in Michigan wrote. A CT scan in the emergency room revealed bilateral pulmonary infiltrates, and the woman required intubation shortly after admission. She was empirically started on piperacillin/tazobactam and linezolid.

Initial bronchial cultures were all negative. The next day, the patient’s blood cultures became positive for Neisseria meningitidis, and her antimicrobials were changed to ceftriaxone. HIV testing was negative.

Several days later, the patient’s condition worsened. Another bronchoscopy was performed, with cultures growing Pseudomonas aeruginosa susceptible to colistin only. She was then transitioned to IV colistin and continued on ceftriaxone. Her mental status subsequently improved after three days, and her family noted she was awake and alert. But the patient then “became minimally responsive with increasing difficulty with oxygenation,” the member wrote. A new CT scan showed a large left upper lobe cavitary pneumonia.

“At that point she was transferred to my facility where ECMO was initiated,” the member noted, and continuous renal replacement therapy was also started. “The patient has continued to require ECMO (now day fourteen) with an inability to mechanically ventilate (Vt <20 ml).” Repeat cultures continue to grow P. aeruginosa “with copious purulent secretions and desquamative appearance to the lung tissue.”

“She has been treated at our facility with  colistin, ceftaz, and rifampin,” the member wrote, with ciprofloxacin and azithromycin also being added recently. “Any thoughts or suggestions would be appreciated.”

An EIN member in Connecticut suggested that fosfomycin might have a role. “It’s not a great stand-alone drug for P. aeruginosa, but it does have some activity and seems to be synergistic with aminoglycosides,” the member noted, citing a 2003 article from the Journal of Cystic Fibrosis, which reported on the use of fosfomycin in cystic fibrosis patients with Pseudomonas infection.

A respondent in Oregon offered a few suggestions to optimize the colistin dosage. “The target is a steady state concentration of 5 ug/ml,” the member wrote. “Serum levels are not routinely available. The best that we have, to date, are the pharmacokinetic studies of Roger Nation. Based on his study of roughly 100 patients, the suggested dosing formula to hit the 5 ug/ml target is: 5((1.5 X CrCl) +30) = the total daily dose. But you have to normalize to Body Surface Area: Total daily dose X patient’s body surface area in M2/1.73 M2. Divide total daily dose into q8h regimen.”

The member noted there is some evidence that “in the presence of the colistin, carbapenems are able to penetrate to their target despite resistance enzymes and efflux pumps,” citing a December 2011 article in Antimicrobial Agents and Chemotherapy. “I would suggest using imipenem or meropenem.”

A member in California called the case a “tragic situation. But I wonder if in the face of such a resistant profile and clinical failure, and empiric therapeutic combinations, whether in vitro studies for synergy or additive effect therapy might be justified.”

Help IDSA address rising drug resistance and the dwindling antimicrobial research and development pipeline by sharing how resistance is impacting your ability to care for patients and by alerting your representatives in Congress to the need for action. Learn more here.


E-mail the Emerging Infections Network.

The Emerging Infections Network (EIN) is a provider-based sentinel network designed to help the public health community detect trends in emerging infectious diseases.

A joint project of IDSA and the Pediatric Infectious Diseases Society (PIDS) with funding from the Centers for Disease Control and Prevention (CDC), EIN tracks emerging infectious diseases and keeps the public health community up to date with new disease trends, difficult cases, and other issues affecting members’ clinical practices. The Network provides a great opportunity for members to share knowledge quickly across large geographical distances. Both IDSA and PIDS members are eligible to join. Click here for more information or to join EIN.

IDSA, SHEA, PIDS Outline National Approach to Antimicrobial Stewardship

A new position paper from IDSA, the Society for Healthcare Epidemiology of America (SHEA), and the Pediatric Infectious Diseases Society (PIDS) outlines measures necessary to improve the use and ensure the impact of antibiotics on emerging health care associated infections. Published in the April issue of Infection Control and Hospital Epidemiology, the paper appears in a special topic issue focused on antimicrobial stewardship.

National initiatives recommended in the paper include:

  • incorporate antimicrobial resistance and antimicrobial stewardship into the curriculum for health care professionals
  • collect data on antimicrobial use in both inpatient and outpatient settings
  • monitor stewardship initiatives in ambulatory and outpatient health care settings
  • require health settings to implement antimicrobial stewardship programs through regulatory mechanisms
  • fill the knowledge gaps in our understanding of antibiotics resistance to increase our understanding of the transmission of resistance

For more information, see the related press release.

C. difficile Infections Growing Threat Across Medical Settings

Infections from C. difficile are a growing threat to patient safety across different medical settings, not just hospitals, according to a new Vital Signs report from the Centers for Disease Control and Prevention (CDC).

Ninety-four percent of such infections are related to medical care, the CDC report found. About 25 percent of C. difficile infections (CDI) first show symptoms in hospital patients; 75 percent first show in nursing home patients or in people recently cared for in doctor’s offices and clinics. CDC’s Safe Healthcare Blog has more on the report and its clinical implications, as does CDC’s website.

Additional resources from IDSA, SHEA, and other partners:

Drug Approvals, Recalls, Adverse Events Update

IDSA offers two email services to help members stay informed of updates from the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). Content includes a range of topics, including new drug approvals and warnings. Recent alerts have included:

IDSA members can sign up for these services online. (To subscribe, check the appropriate boxes to receive CDC’s Health Alert Network (HAN) messages and/or alerts from FDA, and provide your email address and name where indicated.)

Is Your Facility Experiencing Antibiotic Shortages?

IDSA members are urged to report drug shortages directly to FDA and to copy IDSA staff at schang@idsociety.org.

Highlights from CROI 2012 Conference

Science Speaks, the popular blog of the Center for Global Health Policy, provided live coverage of the 19th annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, March 5-8. Check out the blog for reports on the science and news from the conference, including new tools to track AIDS and the global burden of disease, data from pre-exposure prophylaxis and microbicide studies, and much more.

More recent news from Science Speaks:

New Combo Drug Trial Has Potential to Transform TB Treatment

In advance of World Tuberculosis (TB) Day, March 24, the TB Alliance announced the launch of a new trial to test a combination drug regimen in patients with drug-sensitive TB as well as patients with multidrug-resistant (MDR) TB, the first time this has ever been done. Read more on Science Speaks about the announcement, at an event hosted by Christine Lubinski, IDSA vice president of global health.

More recent news from Science Speaks:

Global Health Community Applauds Nomination of Jim Yong Kim, MD, PhD, for World Bank

Check out Science Speaks to learn more about President Obama’s nomination of Jim Yong Kim, MD, PhD, known for his broad development experience and innovative work fighting the spread of AIDS and tuberculosis, for the post of president of the World Bank.

More recent news from Science Speaks:

Patient-Centered Outcomes Research Agenda Should Include ID

IDSA urged the Patient-Centered Outcomes Research Institute to consider ID areas that align with the institute’s priorities and where there are gaps in current evidence that would benefit from patient-centered outcomes research. Critical ID areas include diagnosis and treatment of hepatitis C, reduction of health care-associated infections, and improvement of antimicrobial stewardship. IDSA’s full comments on the institute’s draft research agenda are online (PDF).

Check Out “My IDSA” for Latest Member News

Find the latest membership news on “My IDSA” on the IDSA website, including new IDSA members, the April 2 deadline to submit nominations for the 2012 IDSA Society Awards, and an update on advance access to new articles in The Journal of Infectious Diseases and Clinical Infectious Diseases.

Are you a member on the move? Do you know someone who is? Contact Stephanie Cox at scox@idsociety.org so that we can announce it to our membership.

Advance Access to JID and CID Manuscripts

To speed publication, both The Journal of Infectious Diseases (JID) and Clinical Infectious Diseases (CID) are now posting the author’s version of most manuscripts upon acceptance. The Advance Access section of each journal displays a mix of “Accepted Manuscripts” (manuscripts  that have undergone peer review but have not yet been copyedited) and “Corrected Proofs” (manuscripts that have been copyedited and formatted for publication). Visit the Advance Access section of JID and CID for more information, including how to cite Advance Access articles.

New Pediatric ID Journal Now Available

A new journal focused on perinatal, childhood, and adolescent infectious diseases is now available. The first issue of the Journal of the Pediatric Infectious Diseases Society published earlier this month. The new peer-reviewed journal will publish original research articles, clinical trial reports, guidelines, and topical reviews, with a particular focus on the needs of the pediatric ID community. Theoklis E. Zaoutis, MD, MSCE, associate professor of pediatrics at the Children’s Hospital of Philadelphia, is the editor-in-chief of the quarterly journal.

Journal of the Pediatric Infectious Diseases Society, March 2012 issue

From the President: What’s on Tap for IDWeek 2012, Oct. 17-21

IDSA, HIVMA, SHEA, and PIDS have created a comprehensive program featuring the latest science and a diverse range of bench-to-bedside advances to help IDSA members who want to meet their educational needs, stay current, apply state-of-the-art science to clinical care, and excel in their own careers.

This fall, infectious disease and other health professionals will gather in San Diego for IDWeek 2012, Oct. 17-21, the first joint meeting of IDSA, the HIV Medicine Association (HIVMA), the Society for Healthcare Epidemiology of America (SHEA), and the Pediatric Infectious Diseases Society (PIDS). (Members can register online now; the abstract submission deadline is May 11.)

Why are the nation’s four leading ID organizations holding a joint meeting now? Many of the issues and challenges we face cut across prevention, diagnosis, treatment, and epidemiology of infectious diseases, including HIV infection, for pediatric and adult populations. IDWeek will allow IDSA members and members of our partner organizations to learn from each other’s varied backgrounds, knowledge, experience, and expertise, at one meeting.

Under the theme of “Advancing Care, Improving Science,” the IDWeek partners have created a comprehensive program featuring the latest science and a diverse range of bench-to-bedside advances to help IDSA members who want to meet their educational needs, stay current, apply state-of-the-art science to clinical care, and excel in their own careers. See the Preliminary Program Primer (PDF), featuring the Schedule-at-a-Glance, for an overview, including:

  • A Special Plenary Session featuring Martin Blaser, MD, FIDSA, and a Closing Plenary Session focused on the reemergence of vaccine preventable diseases, featuring Janet A. Englund, MD, FIDSA; Walter Orenstein, MD, FIDSA; and Michael N. Oxman, MD, FIDSA.

  • Updates on antimicrobial resistance and stewardship, health care-associated infections, immunization, influenza, pneumonia, C. difficile, fungal infections, HIV care, global health, clinical practice management, and much more.

  • Several sessions on hepatitis C, including an interactive symposium, part of IDSA’s commitment to develop educational resources to assist members and promote the important role of ID physicians in this area.

  • An update on health care reform and on efforts to document the value ID specialists provide to patients and the health care system, through improved patient outcomes and reduced health care costs.

The broad expertise and diverse memberships of IDSA, HIVMA, PIDS, and SHEA will provide an unparalleled learning and networking opportunity for IDSA members. Stay tuned for more updates in the months ahead, and we hope to see you in San Diego this fall.

New Guideline for Acute Bacterial Rhinosinusitis Now Available

The guideline’s primary focus is to improve the use of first-line antibiotics for patients with a presumptive diagnosis of acute bacterial rhinosinusitis.

IDSA’s new guideline for acute bacterial rhinosinusitis (ABRS) in children and adults is now available online. The guideline also appears in the April 15 issue of Clinical Infectious Diseases.

The guideline’s primary focus is to improve the use of first-line antibiotics for patients with a presumptive diagnosis of ABRS. The guideline’s intended audiences are primary care physicians in the community and the emergency department setting (e.g., family practitioners, internists, and pediatricians).

The reduction of inappropriate use of antimicrobial agents in patients with acute viral rhinosinusitis is emphasized. Additionally, the guideline provides guidance regarding the best clinical characteristics that are most helpful to distinguish bacterial from viral rhinosinusitis at the point of care.

Pitfalls of existing guidelines, due to the inability of current clinical criteria to differentiate bacterial from viral acute rhinosinusitis, are discussed. Gaps in quality evidence regarding empiric antimicrobial therapy for ABRS due to imprecise patient selection criteria are also identified.

The guideline provides key recommendations concerning initial treatment. For example, due to the recent increase in antibiotic resistance, the question regarding the preferred use of amoxicillin vs. amoxicillin-clavulanate for initial empiric antimicrobial therapy of ABRS in adults is addressed. In addition, recommendations regarding the preferred management strategy in patients who worsen despite 72 hours or fail to improve after three to five days of initial empiric antimicrobial therapy with a first-line regimen are provided. An algorithm for patient management based on temporal progression of patient responses is offered.

Therapeutic dilemmas encountered by primary care physicians, such as a lack of precision in current methods of diagnosis and imaging studies of presumed ABRS, are also discussed. 

Several key performance measures are identified in the guideline, including the percent of patients:

  • treated for sinusitis who met the criteria for therapy
  • treated for sinusitis for which the appropriate antimicrobial is used
  • treated for recommended duration of therapy
  • who fail initial therapy and have an appropriate culture obtained

The guideline is available online and is also being developed in both mobile device and pocketcard format for use at the point of care. These and other clinical tools, when available, can be accessed through the practice guidelines section of the IDSA website.

IDSA Proposes New Pathway for Antibiotic Approval,Action from Members Needed

A new antibiotic approval pathway proposed by the Society has potential to be a game changer in antibiotic research and development. IDSA members can make a critical difference in the next few weeks by urging Congress to support enactment of the proposal.

A new antibiotic approval pathway proposed by IDSA earlier this month has strong potential to be a game changer in antibiotic research and development (R&D), by providing an important new approval option for companies interested in developing drugs for serious infections with few or no existing treatment options. Interest on Capitol Hill is growing, and IDSA members can make a critical difference in the next few weeks by urging their representatives in Congress to support enactment of the proposal. (Email your senators and representatives now.) 

IDSA submitted the new concept, the Special Population Limited Medical Use (SPLMU)* drug development pathway, in testimony to a U.S. House Energy and Commerce Health Subcommittee hearing on the Prescription Drug User Fee Act (PDUFA) reauthorization on March 8. Using the SPLMU mechanism, the drug's safety and effectiveness would be studied in substantially smaller, more rapid, and less expensive clinical trials than traditionally required. In return, the drug would be narrowly indicated for use in a small, specific population of patients for whom the benefits of the drug have been shown to outweigh the risks.

The designation, a special logo, a description of the population in which the drug is indicated, and the rationale for limiting use to that population would appear in the drug's labeling. The SPLMU mechanism would foster prudent use of anti-infective drugs to slow the rate at which resistance to the drugs develops. The proposal has received considerable media coverage, including from Reuters and outlets covering Capitol Hill.

On March 30, IDSA and Trust for America’s Health (TFAH) will hold a briefing in Washington, D.C., for congressional staff on the proposal and why it is so critical that it be included in legislation reauthorizing PDUFA. Speakers will include Janet Woodcock, MD, director of Center for Drug Evaluation and Research at the Food and Drug Administration; Brad Spellberg, MD, FIDSA, co-chair of IDSA’s Antimicrobial Availability Task Force; and Jeff Levi, PhD, TFAH’s executive director.

Additional Information

 

* Editor's Note (04/05/2012): The proposed new drug approval pathway is now known as the Limited Population Antibacterial Drug (LPAD) approval mechanism.


 

IDSA Journal Club

March 2012

This month, studies investigating S. aureus decolonization for the prevention of recurrent SSTI in children; amoxicillin and acute sinusitis; treatment for acute uncomplicated cystitis; and accessibility to fecal transplantation for C. difficile infections.

In this feature, a panel of IDSA members identifies and critiques important new studies in the current literature that have a significant impact on the practice of infectious diseases medicine.

Click here for the previous edition of Journal Club. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.


S. aureus Decolonization for the Prevention of Recurrent SSTI in Children
Reviewed by Kathryn E. Stephenson, MD, MPH

Community-associated Staphylococcus aureus causes an increasing number of recurrent skin and soft tissue infections (SSTI), particularly among children. S. aureus transmission in the community is not well-characterized, but recurrent infections in children may be due to continued exposure to S. aureus-colonized household contacts.

In the March 15 issue of Clinical Infectious Diseases, researchers report the results of a randomized clinical trial of 183 pediatric patients with S. aureus SSTI, comparing two approaches to eradicating S. aureus: decolonizing the case alone versus decolonizing the entire household. Decolonization involved five days of mupirocin to the nares, showers/baths with Hibiclens, and standardized hygiene recommendations. The authors found that, one month after randomization, there was no difference in S. aureus eradication rates between the household group (51 percent) and the index group (50 percent, P = 1.00). Cases in the household group, however, were less likely than those in the index group to report recurrent SSTI after three months (28 percent vs. 47 percent; P = 0.02), six months (38 percent vs. 61 percent; P = 0.008), and 12 months (52 percent vs. 72 percent; P = 0.02). The authors conclude that decolonization of the entire household reduces the risk of recurrence of S. aureus SSTI in children.

The study’s strength is its randomized trial design, but its scope is limited. The results may not extend to adults, and the study did not address the fundamental question as to whether decolonization of the patient reduces subsequent S. aureus SSTI. In addition, as the authors emphasize, considerable improvement in S. aureus SSTI prevention is still needed, as more than 50 percent of cases in the household group reported recurrent SSTI over a one-year period.

 (Fritz et al. CID 2012:54:743-51.)

back to top


Amoxicillin Alone Doesn’t Help Patients with Acute Sinusitis
Reviewed by Jason B. Weinberg, MD

A 10-day course of amoxicillin is no better than placebo at quickly improving symptoms in patients with acute rhinosinusitis, according to a study in the Feb. 15 issue of the Journal of the American Medical Association (JAMA).

Antibiotics are frequently prescribed for patients with sinusitis despite a lack of convincing evidence demonstrating their efficacy.  In addition, previous work suggests that many patients improve spontaneously without antibiotic therapy.  To determine whether antibiotic treatment had any effect on clinical outcomes, the authors of this study conducted a randomized, placebo-controlled trial in which 166 adult patients diagnosed with acute rhinosinusitis received either 10 days of amoxicillin or placebo in addition to symptomatic therapy.

The investigators assessed the primary outcome, sinusitis symptom severity and frequency, using the (brilliantly named) modified Sinonasal Outcome Test-16 (SNOT-16) scoring tool.  SNOT-16 scores and overall patient-reported improvement in symptoms were similar in amoxicillin and placebo groups on days 3 and 10 of therapy. Although scores were slightly better in patients receiving amoxicillin on day 7, the magnitude of this effect was not likely to be clinically significant. There were no differences between groups in satisfaction with treatment, missed days of work, disease relapse or recurrence, or adverse events.

Patients included in the study had at least 7 days of symptoms that were not improving or worsening, and the authors suggest that they were representative of patients who might receive antibiotics in general practice. Although the disease process is likely to be similar in pediatric patients, no children were included in the study. Importantly, the study also did not include patients with serious complications from sinusitis, a group for whom antibiotics are still likely to be beneficial. However, the results of this study suggest that amoxicillin therapy does not provide a substantial clinical benefit to the majority of patients with acute sinusitis.

IDSA clinical practice guidelines for acute bacterial rhinosinusitis released after this article was published advocate treating adult and pediatric patients who have persistent (≥10 days), severe, or worsening symptoms with amoxicillin/clavulanate. Because the JAMA study included some patients with a shorter duration of symptoms (<10 days) and treated patients with amoxicillin instead of amoxicillin/clavulanate, it is difficult to predict how they would have fared if treated according to the new guidelines. The consistent application of consensus definitions for the diagnosis of acute bacterial rhinosinusitis will be important for ongoing evaluation of the new practice guidelines.

(Garbutt et al. JAMA 2012; 307(7):685-92.)

back to top


Treatment for Acute Uncomplicated Cystitis: Cefpodoxime vs. Ciprofloxacin
Reviewed by Kathryn E. Stephenson, MD, MPH

Fluoroquinolones are a popular antimicrobial choice for the treatment of uncomplicated cystitis because they are highly effective and have minimal side effects. There has been growing concern, however, that widespread fluoroquinolone use is leading to dangerous bacterial drug resistance within our environment. Cefpodoxime is an oral third-generation cephalosporin with fewer ecological adverse effects that has been proposed as a potential alternative to fluoroquinolones for the treatment of cystitis.

In the Feb. 8 issue of The Journal of the American Medical Association, a report describes the results of a randomized double-blind non-inferiority trial of 300 women with acute uncomplicated cystitis comparing 250 mg of ciprofloxacin to 100 mg of cefpodoxime, taken orally twice a day for three days. The primary outcome was clinical cure at the 30-day follow up visit; clinical cure was defined as not needing repeat antimicrobial therapy. The authors found that in the intent-to-treat analysis, patients having clinical cure was 93 percent for ciprofloxacin compared with 82 percent for cefpodoxime (P = .57). Study outcomes were not changed by the per-protocol analysis. In addition, 16 percent of women in the ciprofloxacin group compared with 40 percent in the cefpodoxime group had vaginal Escherichia coli colonization at the first follow-up visit.

This study demonstrates in an elegant fashion that cefpodoxime is not as effective as ciprofloxacin for the treatment of acute cystitis. The authors speculate that the reason cefpodoxime fails more often than ciprofloxacin is because it is not as effective at eradicating uropathogens from vaginal flora.

(Hooton et al. JAMA 2012:307:583-9.)

back to top


Improving Accessibility to Fecal Transplantation for C. difficile Infections
Reviewed by Jonathan Li, MD

Fecal bacteriotherapy, commonly known as fecal or stool transplants, has been demonstrated in small studies to be a safe and efficacious method of treating recurrent C. difficile infection (CDI). Despite impressive outcomes and significant clinical need, the availability of fecal transplantation is limited by both practical (e.g., aesthetics and equipment/space for stool processing) and reimbursement (e.g., cost of donor screening) concerns. Two recent studies describe streamlined procedures that may help lower these barriers. 

In a study published online in the American Journal of Gastroenterology in January, researchers describe 43 patients treated with fecal microbiota transplantation (FMT) including the use of standard volunteer fecal donors and the banking of frozen processed fecal material. All patients had to have at least two documented recurrences, at least one of which was on a long vancomycin course and/or with a rifaximin “chaser.”

Overall, patients had a mean of almost six CDI recurrences over 12 months. There was no significant difference in the initial success rates at two months by type of donor material: 70 percent (7/10) in those receiving stool from a personalized donor, 92 percent (11/12) in participants receiving fresh material from a standard donor, and 90 percent (19/21) in those receiving previously frozen fecal material from a standard donor. In the six individuals with recurrence despite FMT, four elected to retry the procedure with standard donor stool, and all were successfully cured. The use of frozen fecal material from standard donors was preferred by the patients and removed significant practical barriers to FMT while reducing the costs associated with screening potential donors.

In a research letter published in the Jan. 23 issue of the Annals of Internal Medicine, investigators report the efficacy of standard donor fecal transplantation by rectal retention enema in 27 patients with refractory or recurrent CDI. The mean duration of diarrhea was 153 days. After one fecal transplant, 81 percent (22/27) of participants experienced clinical resolution of symptoms within seven days. The remaining five patients received a second stool enema, with three patients experiencing symptom resolution and a total clinical response rate of 93 percent (25/27). No additional relapses or adverse events were reported with a mean 427 days of follow-up after transplant. 

While both studies are relatively small, the protocols they describe may help overcome some of the practical and cost challenges limiting use of fecal transplantation for recurrent CDI and could play a role in improving patient access to these potentially life-saving therapies.

(Hamilton et al. Am J Gastroenterol. 2012; doi: 10.1038/ajg.2011.482. published online Jan. 31, 2012 and Kassam et al. Arch Intern Med. 2012;172(2):191-3.)

back to top

For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

March 15

  • The Black Death and Modern Plague
  • Acute Drug-Induced Liver Injury—Some Cases May Actually Be Due to Hepatitis E Virus Infection

March 1

  • What’s in a Name? Canis Lupus Familiaris Hosts Rickettsia Felis
  • Men (and Women) Are Not Mice—Deferasirox Fails as Adjunctive Treatment of Mucormycosis
  • Cytotoxic Antiviral Therapy of Multicentric Castleman Disease