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.
Isavucanzole as Another Option for Treatment of Mucormycosis |
Reviewed by Lauren Richey, MD, MPH
for mucormycosis, an opportunistic fungal infection associated with
immunosuppressed patients, is poor, and mortality rates can exceed 90 percent.
Present therapy consists of antifungal treatment, generally with amphotericin
B, in combination with surgical debridement and treatment of the underlying
disorder. Few other treatment options
currently exist. The recent VITAL study, published in Lancet Infectious Diseases, tested the use of isavuconazole, a new
triazole antifungal with activity against Mucorales
species and high oral bioavailability, in patients with mucormycosis. The drug has both an oral and intravenous
study, 37 patients with proven or probable mucormycosis were recruited and
treated with isavuconazole, including both those with pulmonary and
non-pulmonary disease. The majority, 21 (57 percent), were in the primary
treatment group, but the total group also included 11 with refractory disease
and five patients who were intolerant to other antifungals. An independent data
review committee determined the primary efficacy endpoint of overall response
at day 42. Four patients (11 percent) had a partial response, 16 (43 percent)
had stable disease, one (3 percent) had progression of disease, 13 (35 percent)
had died, and three (8 percent) had missing data. A high rate of adverse events
was seen (95 percent). The most common were vomiting, diarrhea, nausea,
pyrexia, and constipation, with elevated hepatic enzymes seen in less than 10
percent of patients.
case control analysis was also performed using patients from the FungiScope
registry. Cases were matched on three variables: hematologic disease, severe
disease (defined as central nervous system involvement or dissemination), and
surgical treatment within seven days of antifungal treatment initiation. The
authors found a similar crude mortality rate between the groups at day 42, 33
percent for cases and 41 percent for controls.
provides evidence that isavuconazole has a role in the treatment of both
primary and refractory disease with mucormycosis, with outcomes that are likely
similar to amphotericin. The study is limited by being single-armed and
non-randomized, but it does suggest another treatment option.
(Marty et al. Lancet Infect Dis. 2016;16(7):828–837.)
Neurologic Signs and Symptoms Common in Acute HIV Infection
Reviewed by Kelly Cawcutt, MD
invade the central nervous system rapidly after infection, but knowledge is
limited regarding neurologic manifestations of acute HIV infection beyond
fulminant diseases, such as Guillain-Barré syndrome, Bell’s palsy,
encephalitis, or myelitis, which may not represent the true spectrum of
disease. To better define the neurologic complications, the authors of a recent Neurology article prospectively evaluated adult
patients with acute HIV from a single center in Thailand who were started on
early antiretroviral therapy (ART) and evaluated via structured neurologic
evaluations over 12 weeks.
Of the 197
patients enrolled, 139 had complete data with a median estimated duration of
HIV infection of 19 days (range of 3-56). Of these, 73 (53 percent) had at
least one positive neurologic finding reported or identified. Only one patient
had a fulminant neurologic process identified as Guillain-Barré. There were 245
positive neurologic findings, with 96 percent categorized as mild. The most
common findings were defined as cognitive (33 percent) and motor (34 percent).
Approximately half (49 percent) of the neurologic findings were noted at the
time of HIV diagnosis, prior to initiation of ART, and improved with one month
of treatment. Of note, no structural abnormalities were found. Patients with
neurologic findings demonstrated a statistically significant higher viral load
as compared to those without (p=0.006).
study demonstrates that mild neurologic findings are common in the first 12
weeks after acute HIV infection, are correlated with higher viral loads, and
usually improve after initiation of ART. Severe manifestations, or fulminant
neurologic disease, are rare in acute HIV infection.
The study is
limited with the ability to comment on association but not causality. There is
a lack of control arms with uninfected controls or infected participants not
started on ART, thus the authors cannot attribute neurologic findings directly
to HIV or improvements to ART. Illicit drug use may also have confounded the
results. The study does however raise important awareness about the possibility
of early neurologic manifestations and warrants future studies to better define
et al. Neurology. 2016;87(2):148-54.)
Prevention of Mother-to-Child Hepatitis B Transmission with Tenofovir
Reviewed by George R. Thompson III, MD
transmission of hepatitis B virus (HBV) occurs in 80-90 percent of infants born
to mothers who are positive for hepatitis B e antigen (HBeAg). The efficacy of
postnatal passive and active immunization reduces the rate of mother-to-child
transmission, however this practice fails a significant number of infants.
Prenatal antiviral treatment has the potential to further reduce transmission.
The results of a
recent study evaluating the efficacy tenofovir disoproxil fumarate (TDF) for the
prevention of maternal hepatitis B transmission were recently published in the New England Journal of Medicine. In this study, 200 women were
randomly assigned in a 1:1 ratio to an oral dose of 300 mg of TDF or usual care
without antiviral therapy beginning 30-32 weeks of gestation until postpartum
week 4. Infants in both groups received 200 IU of hepatitis B immune globulin
IM and 10 ug of the HBV vaccine within 12 hours of birth. The same dose of
active or passive immunization was administered at week 4 and an additional HBV
vaccination at week 24.
In the primary
outcomes, the rate of mother-to-child transmission was significantly lower in
the TDF group than in the control group, in both the intention to treat
analysis (5 percent vs. 18 percent, p=0.007) and the per-protocol analysis (0
percent vs. 7 percent, p=0.01). Maternal and infant safety profiles were
similar in both groups with no significant differences in birth-defect rates between
groups. Maternal HBV serologic outcomes
(loss or seroconversion of HBeAg or HBsAg) did not significantly differ between
illustrates the utility of TDF for the prevention of hepatitis B transmission
with a favorable side effect profile. Although the serologic status did not
differ between groups, this was not unexpected given the relatively short
(approximately 12 weeks) duration of therapy.
(Pan et al. N Engl J Med. 2016;374:2324-34.)
For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, FIDSA, in each issue of Clinical Infectious Diseases: August 1
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