Fidaxomicin versus conventional antimicrobial therapy in 59 recipients of solid organ and hematopoietic stem cell transplantation with Clostridium difficile-associated diarrhea.

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Clutter DS, Dubrovskaya Y, Merl MY, Teperman L, Press R, Safdar A.

Antimicrob Agents Chemother. 2013 Sep;57(9):4501-5.

The feasibility of fidaxomicin versus vancomycin and metronidazole (conventional
therapy) was assessed in 59 transplant recipients with 61 episodes of Clostridium
difficile-associated diarrhea (CDAD). Overall clinical cure was achieved in 86%
of episodes, and in 7% of episodes, infection recurred. Fidaxomicin was well
tolerated. Clinical cures were not significantly different compared with
conventional therapy (67% versus 89%, respectively; P = 0.06). Univariate
analysis of predictors for lack of clinical cure included continued use of
broad-spectrum systemic antibiotics (P = 0.026) and prior diagnosis of CDAD (95%
confidence interval, 1.113 to 19.569; odds ratio, 4.667; P = 0.041). New-onset
vancomycin-resistant Enterococcus (VRE) colonization was not noted after
fidaxomicin therapy alone. However, this occurred in 10 of 28 patients (36%)
following conventional therapy, and 2 of 3 patients with subsequent bacteremia
died.

Use of healthy-donor granulocyte transfusions to treat infections in neutropenic patients with myeloid or lymphoid neoplasms: experience in 74 patients treated with 373 granulocyte transfusions.

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Safdar A(1), Rodriguez G, Zuniga J, Al Akhrass F, Pande A.

Acta Haematol. 2014;131(1):50-8.

BACKGROUND/AIMS: Despite limited evidence for efficacy, granulocyte transfusions
(GTX) are used to prevent and treat opportunistic infections in patients with
neutropenia.
METHODS: Three hundred and seventy-three GTX given to 74 patients were assessed
retrospectively.
RESULTS: GTX were discontinued because of clinical improvement more often in
patients with severe infections than in patients without severe infections (27
vs. 12%; p ≤ 0.002), whereas deaths resulted in discontinuation of GTX therapy
less often in patients with severe infections than without (8 vs. 39%; p ≤
0.002). Patients who died by 12 weeks after GTX initiation were more likely to
have leukemia (p = 0.03), not to have recovery of neutrophil counts (p < 0.0001),
and to have started GTX during a critical care unit stay (p < 0.001). Uses of
granulocyte colony-stimulating factor (p ≤ 0.02) and interferon-γ (p ≤ 0.04) were
more common in patients who survived. In patients with comorbidities (31%; odds
ratio, OR, 12.6; 95% confidence interval, CI, 2.4-65.7; p ≤ 0.003), GTX was
started in the critical care unit (OR 8.8; 95% CI 2.5-30.9; p < 0.001), and a
high total bilirubin level at the end of GTX (OR 2.1; 95% CI 1.1-4.2; p = 0.03)
had a higher probability of death 12 weeks after GTX therapy commenced.
CONCLUSIONS: The possibility that a niche population may benefit from GTX
requires further assessment.

Impact of cytotoxic and targeted antineoplastic drugs on the validity of the mitogen-induced interferon-gamma release assay for latent tuberculosis infection: results of a prospective trial at a comprehensive cancer center.

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Rodriguez GH, Safdar A.

Scand J Infect Dis. 2014 Jan;46(1):52-7.

Abstract The T-SPOT.TB test (TS.TB), an interferon-gamma (IFN-γ) release assay
(IGRA), is superior in diagnosing latent tuberculosis infection compared with the
conventional tuberculin skin test (TST). However, whether cytotoxic chemotherapy
and treatment with new-generation antineoplastic monoclonal antibodies affects
the TS.TB is not certain. We evaluated the feasibility of using the TS.TB in this
population. Sixteen cancer patients at high risk for tuberculosis exposure were
prospectively evaluated with the TST and TS.TB. Blood samples were obtained 7.5 ±
89.3 days after the most recent cycle of antineoplastic therapy. Six patients
(38%) were febrile within 24 h of blood sampling; high-dose corticosteroid
therapy and profound treatment-induced neutropenia were present in 1 patient
each. In all patients, TS.TB showed no evidence of latent tuberculosis infection.
A robust mitogen-induced IFN-γ response was seen in samples from 14 patients
(88%) despite therapy with high-dose corticosteroids, cyclophosphamide,
fludarabine, gemtuzumab ozogamicin, and alemtuzumab. The presence of fever or
profound neutropenia did not negatively impact mitogen response by peripheral
lymphocytes. The 2 patients whose peripheral blood lymphocytes (> 500 cells/ml)
failed to generate a cytokine response to ex vivo mitogen stimulation had
refractory advanced cancer. Unlike the TST, a negative TS.TB provided
interpretable results even in cancer patients undergoing new-generation
immunosuppressive therapy.

High-dose caspofungin as a component of combination antifungal therapy in 91 patients with neoplastic diseases and hematopoietic stem cell transplantation: a critical review of short-term and long-term adverse events.

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Safdar A, Rodriguez G, Zuniga J, Al Akhrass F, Pande A.

J Pharm Pract. 2015 Apr;28(2):175-82.

The antifungal activity of echinocandins is concentration dependent. Previously,
we demonstrated that high-dose caspofungin (HD-CSP; 100 mg daily) was well
tolerated in 34 immunosuppressed patients with cancer and may have favorably
influenced outcomes. We retrospectively assessed all 91 patients in whom HD-CSP
was given for the treatment of invasive fungal disease (IFD). The median number
of doses was 18.5 ± 21.5, and in 8 (9%) patients more than 40 doses were given.
Most (62%) of the patients had leukemia. A total of 45 (49%) patients had
undergone stem cell transplantation; 80% received allogeneic grafts and 47% had
graft-versus-host disease. High-dose corticosteroids were given during antifungal
therapy in 26 (29%) patients. In all, 8 (9%) patients had new elevation in serum
bilirubin during HD-CSP therapy; normalization occurred after voriconazole and
HD-CSP were discontinued in 4 patients each. No other short-term or delayed
adverse events were observed. In all, 40 (44%) patients died of IFD. High-dose
corticosteroids during HD-CSP (odds ratio [OR] 8, 95% confidence interval [CI]
2.1-30.4; P < .002) and starting HD-CSP in the critical care unit (OR 67.5, 95%
CI 5.25-868.9; P < .001) were associated with death from fungal disease.
Prolonged HD-CSP therapy was well tolerated. Drug-induced hyperbilirubinemia may
pose a potential limitation for continued HD-CSP use in highly susceptible
patients with hematologic neoplasms and stem cell transplantation.

Fidaxomicin therapy in critically ill patients with Clostridium difficile infection.

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Penziner S1, Dubrovskaya Y1, Press R1, Safdar A2.   2015 Mar;59(3):1776-81. 
Abstract
Fidaxomicin use to treat proven Clostridium difficile infection (CDI) was compared between 20 patients receiving care in critical care units (CCUs) and 30 patients treated on general medical floors. At baseline, the CCU patients had more initial CDI episodes, more severe and complicated disease, and more concurrent broad-spectrum antibiotic coverage. On multivariate analysis, the response to fidaxomicin therapy among the critically ill patients was comparable to that among patients in the general medical wards.

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