- Infectious Disease
- Immunocompromised Host Infectious Disease
- Mycobacterium Infections, Nontuberculous
- Nocardia Infections
- Bronchiolitis Obliterans
- Graft Versus Host Disease
Clinical Assistant Professor, Medicine - Infectious Diseases
Medical Education: Boston University School of Medicine (2011) MA
Fellowship, Stanford University, Immunocompromised Host Infectious Diseases Fellowship (2017)
Board Certification: American Board of Internal Medicine, Infectious Disease (2016)
Fellowship: NYU Medical Center/Bellevue Hospital (2016) NY
Board Certification: American Board of Internal Medicine, Internal Medicine (2014)
Residency: UCLA Medical Center Internal Medicine (2014) CA
- Sternal wound infection with Mycoplasma salivarium following bilateral lung transplant. Transplant infectious disease : an official journal of the Transplantation Society 2023: e14120
Noninfectious causes of fever in hematologic malignancies. Are antibiotics still indicated?
Current opinion in infectious diseases
2023; 36 (4): 209-217
PURPOSE OF REVIEW: Fever is a common manifestation of both infectious and noninfectious processes in recipients of hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy. Understanding the diverse causes of fever in these settings allows for accurate diagnosis and optimal use of antibiotics.RECENT FINDINGS: Herein we review common noninfectious syndromes seen in HCT and CAR-T recipients and discuss best practices in the management of these complex clinical scenarios regarding diagnosis and antibiotic use. In recent years, adverse effects of antimicrobials have highlighted the importance of antimicrobial stewardship in HCT and CAR-T patients, and an antibiotic de-escalation strategy is a safe and important tool in mitigating these adverse events, even in patients with ongoing neutropenia who become afebrile without a known infection. Common adverse events associated with antibiotics include an increased risk of Clostridiodes difficile infection (CDI), a higher incidence of multidrug-resistant organisms (MDROs), and microbiome dysbiosis.SUMMARY: Clinicians should be aware of noninfectious causes of fever in these immunocompromised patients and utilize best antibiotic practices while managing these patients.
View details for DOI 10.1097/QCO.0000000000000940
View details for PubMedID 37431551
Epidemiology of lower respiratory tract infections and community-acquired respiratory viruses in patients with bronchiolitis obliterans syndrome after hematopoietic cell transplant: a retrospective cohort study.
Transplantation and cellular therapy
Among 55 patients with bronchiolitis obliterans syndrome, 34 (61.8%) developed lower respiratory tract infections, which were associated with impaired lung function and a trend toward increased mortality. Rhinovirus/enterovirus and Pseudomonas aeruginosa infections predominated; 10 (18.2%) patients developed non-tuberculous mycobacterial infections.
View details for DOI 10.1016/j.jtct.2022.07.016
View details for PubMedID 35872303
Epidemiology of invasive fungal diseases in adults with newly diagnosed acute myeloid leukemia.
Leukemia & lymphoma
Invasive fungal diseases (IFDs) are common in patients with acute myeloid leukemia (AML), but no recent data on incidence without antifungal prophylaxis are available. We evaluated the incidence of IFDs in patients with AML undergoing induction chemotherapy at Stanford University Hospital from 2012 to 2017, for up to 12weeks after induction. We also analyzed factors associated with IFD development. Thirty-six of 240 patients (13%) developed at least one proven or probable IFD. Seventy-eight percent of the proven or probable IFDs were due to Candida or Aspergillus species. Infection due to Fusarium and Mucorales was uncommon. Absolute neutrophil count (ANC) of <500L/L at the start of induction was associated with an increased risk of IFD. One hundred and eighty-seven patients (78%) were started on systemic antifungal drugs, even without microbiologic evidence of an IFD. IFDs remain frequent in AML patients undergoing induction chemotherapy without antifungal prophylaxis.
View details for DOI 10.1080/10428194.2022.2060504
View details for PubMedID 35410569
Accuracy of Pneumocystis jirovecii Plasma Cell-Free DNA PCR for Noninvasive Diagnosis of Pneumocystis Pneumonia.
Journal of clinical microbiology
Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii is a serious infection in immunocompromised hosts which requires prompt diagnosis and treatment. The recommended specimen for diagnosis of PCP is bronchoalveolar lavage (BAL) fluid, which is invasive and may not be possible in unstable patients. The aim of this study was to evaluate the accuracy of noninvasive P. jirovecii plasma cell-free DNA (cfDNA) PCR using recently optimized preanalytical and analytical methods. Adult patients undergoing clinical testing for PCP with direct fluorescent antibody stain (DFA), respiratory PCR, and/or beta-d-glucan were included in this study. Sensitivity and specificity P. jirovecii plasma cfDNA PCR was determined in PCP suspects categorized as proven and probable. A total of 149 patients were included in this study, of which 10 had proven and 27 had probable PCP. Most patients (95.9%, 143/149) were immunocompromised, including hematological malignancies (30.1%), bone marrow transplant (11.2%), solid organ transplantation (47.6%), and HIV/AIDS (4.2%). P. jirovecii plasma cfDNA PCR showed sensitivity and specificity of 100% (10/10; 95% confidence interval [CI], 69.2 to 100) and 93.4% (127/136; 95% CI, 87.8 to 96.9), and 48.6% (18/37; 95% CI, 31.9 to 65.6) and 99.1% (108/109; 95% CI, 94.9 to 100) in proven and proven/probable cases, respectively. P. jirovecii cell-free DNA PCR was similar in sensitivity but with substantially improved specificity over beta-d-glucan (sensitivity, 60.0% [18/30; 95% CI, 40.6 to 77.3]); specificity, 66.7% [22/33; 95% CI, 48.2 to 82.0]) in patients with proven/probable PCP. Plasma cfDNA PCR offers a noninvasive testing option for early and accurate diagnosis of PCP, particularly in patients who cannot tolerate bronchoscopy.
View details for DOI 10.1128/jcm.00101-22
View details for PubMedID 35387472
Surgical resection for patients with pulmonary aspergillosis in the national inpatient sample.
Journal of thoracic disease
2021; 13 (8): 4977-4987
The role of lung resection in patients with pulmonary aspergillosis is generally reserved for those with localized disease who fail medical management. We used a national database to investigate the influence of preoperative patient comorbidities on inpatient mortality and need for surgery.Patients admitted with pulmonary aspergillosis between 2007 to 2015 were identified in the National Inpatient Sample dataset. Inpatient mortality rates were compared between patients treated medically and surgically. Predictors of mortality, surgical intervention, and non-elective admission were evaluated using multivariable logistic regression.Among a population estimate of 112,998 patients with pulmonary aspergillosis, 107,606 (95.2%) underwent medical management alone and 5,392 (4.8%) underwent surgical resection. Positive predictors for surgery included hemoptysis, and history of lung cancer or chronic pulmonary diseases. Surgically treated patients had a lower inpatient mortality when compared to those treated medically (11.5% vs. 15.1%, P<0.001) in univariate analysis, but this finding did not persist in multivariable analysis (AOR 0.97, P=0.509). The odds of mortality were lower in patients undergoing video assisted thoracoscopic surgery compared to an open approach (AOR 0.77, P=0.001). Among patients treated surgically, mortality was higher in those with a history of lung cancer, solid organ transplantation, liver disease, human immunodeficiency virus infection, hematologic diseases, chronic pulmonary diseases, and those admitted non-electively requiring surgery.In this generalizable study, medical and surgical management of pulmonary aspergillosis were comparable in terms of inpatient mortality. However, non-elective admission and patients with select comorbidities have significantly worse outcomes after surgical intervention.
View details for DOI 10.21037/jtd-21-151
View details for PubMedID 34527336
View details for PubMedCentralID PMC8411153
Safety and efficacy of intravenously administered cidofovir in adult haematopoietic cell transplant recipients: a retrospective multicentre cohort study.
The Journal of antimicrobial chemotherapy
OBJECTIVES: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT).METHODS: This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT).RESULTS: We included 165 patients from nine centres. Cidofovir was administered at 5mg/kg/week (N = 115; 69.7%), 1mg/kg/week (18; 10.9%), 3mg/kg/week (12; 7.3%) or 1mg/kg three times/week (11; 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04; P = 0.05), weight (OR 1.05; P = 0.01), CMV infection (OR 3.6; P = 0.02), liposomal amphotericin B (OR 8.06; P = 0.05) and IV voriconazole/posaconazole (OR 13.0; P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95mg/dL) compared with baseline (0.91 ± 0.39mg/dL; P < 0.001), but improved by 2weeks (0.91 ± 0.84mg/dL; P = 0.007) and 4weeks (0.96 ± 0.89mg/dL; P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P < 0.0001) and for patients with CMV DNAaemia by EOT + 4weeks (P = 0.003), but not for patients with BK virus DNAaemia.CONCLUSIONS: One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.
View details for DOI 10.1093/jac/dkab259
View details for PubMedID 34324678
- Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma BLOOD ADVANCES 2021; 5 (1): 143–55
Nocardiosis in Immunocompromised Patients on Alternative Pneumocystis Prophylaxis.
Emerging infectious diseases
2021; 27 (10): 2734-2736
Prophylactic trimethoprim/sulfamethoxazole (TMP/SMX) prevents Pneumocystis jirovecii pneumonia and nocardiosis in immunocompromised patients but sometimes is avoided because of purported allergies or side effects. Of 25 immunocompromised patients receiving alternative prophylaxis in whom nocardiosis developed, 16 subsequently tolerated TMP/SMX treatment. Clinicians should consider TMP/SMX allergy evaluation and rechallenging to assess patient tolerance.
View details for DOI 10.3201/eid2710.210620
View details for PubMedID 34545802
View details for PubMedCentralID PMC8462344
Fungal prostatitis due to endemic mycoses and Cryptococcus: A multicenter case series.
Fungal prostatitis is exceedingly rare with mostly case reports.Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years.Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable.Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.
View details for DOI 10.1002/pros.24034
View details for PubMedID 32572997
- Eremothecium coryli bloodstream infection in a patient with acute myeloid leukemia: first case report of human infection DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE 2019; 95 (1): 77–79
Missed diagnosis and misdiagnosis of infectious diseases in hematopoietic cell transplant recipients: an autopsy study.
2019; 3 (22): 3602–12
Hematopoietic cell transplantation (HCT) is potentially curative for patients with hematologic disorders, but carries significant risks of infection-related morbidity and mortality. Infectious diseases are the second most common cause of death in HCT recipients, surpassed only by progression of underlying disease. Many infectious diseases are difficult to diagnose and treat, and may only be first identified by autopsy. However, autopsy rates are decreasing despite their value. The clinical and autopsy records of adult HCT recipients at our center who underwent autopsy between 1 January 2000 and 31 December 2017 were reviewed. Discrepancies between premortem clinical diagnoses and postmortem autopsy diagnoses were evaluated. Of 185 patients who underwent autopsy, 35 patients (18.8%) had a total of 41 missed infections. Five patients (2.7%) had >1 missed infection. Of the 41 missed infections, 18 (43.9%) were viral, 16 (39.0%) were fungal, 5 (12.2%) were bacterial, and 2 (4.9%) were parasitic. According to the Goldman criteria, 31 discrepancies (75.6%) were class I, 5 (12.2%) were class II, 1 (2.4%) was class III, and 4 (9.8%) were class IV. Autopsies of HCT recipients frequently identify clinically significant infectious diseases that were not suspected premortem. Had these infections been suspected, a change in management might have improved patient survival in many of these cases. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality. Illustrative cases are presented and the lessons learned from them are also discussed.
View details for DOI 10.1182/bloodadvances.2019000634
View details for PubMedID 31743391
- Use of Alternative Agents for Prevention of Opportunistic Infections in Heart and Lung Transplant Recipients CLINICAL INFECTIOUS DISEASES 2018; 67 (10): 1637–39
Echinocandin prophylaxis in patients undergoing haematopoietic cell transplantation and other treatments for haematological malignancies.
The Journal of antimicrobial chemotherapy
2018; 73 (suppl_1): i60–i72
Antifungal prophylaxis is the standard of care for patients undergoing intensive chemotherapy for haematological malignancy or haematopoietic cell transplantation (HCT). Prophylaxis with azoles reduces invasive fungal infections and may reduce mortality. However, breakthrough infections still occur, and the use of azoles is sometimes complicated by pharmacokinetic variability, drug interactions, adverse events and other issues. Echinocandins are highly active against Candida species, including some organisms resistant to azoles, and have some clinical activity against Aspergillus species as well. Although currently approved echinocandins require daily intravenous administration, the drugs have a favourable safety profile and more predictable pharmacokinetics than mould-active azoles. Clinical data support the efficacy and safety of echinocandins for antifungal prophylaxis in haematology and HCT patients, though data are less robust than for azoles. Notably, sparse evidence exists supporting the use of echinocandins as antifungal prophylaxis for patients with significant graft-versus-host disease (GvHD) after HCT. Two drugs that target (1,3)-β-d-glucan are in development, including an oral glucan synthase inhibitor and an echinocandin with unique pharmacokinetics permitting subcutaneous and weekly administration. Echinocandins are a reasonable alternative to azoles and other agents for antifungal prophylaxis in patients undergoing intensive chemotherapy for haematological malignancy or those receiving HCT, excluding those with significant GvHD.
View details for PubMedID 29304213
Prevention and Management of Tuberculosis in Solid Organ Transplant Recipients.
Infectious disease clinics of North America
2018; 32 (3): 703–18
Solid organ transplant recipients are at an increased risk of tuberculosis and transplant candidates should be screened early in their evaluation with a detailed history, tuberculin skin test or tuberculosis interferon-gamma release assay, and chest radiograph. For latent tuberculosis treatment, isoniazid and rifamycin-based regimens have advantages and disadvantages; treatment decisions should be customized. Tuberculosis after solid organ transplantation generally occurs after months or years; early infections should raise the possibility of donor-derived infections. Tuberculosis diagnosis and treatment in solid organ transplant recipients may be complicated by protean manifestations, drug interactions, and adverse drug reactions.
View details for PubMedID 30146031
Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management.
Open forum infectious diseases
2018; 5 (8): ofy174
Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.
View details for PubMedID 30094293
View details for PubMedCentralID PMC6080056
HHV-6 and Septic Shock: Tenuous Proof of Causation.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Bonnafous and others present the case of a patient who became ill three weeks after liver transplantation, developing multiple organ failure and episodes of apparent septic shock culminating in death. The authors attribute the illness to reactivation of donor-derived chromosomally-integrated human herpesvirus 6 (HHV-6) infection.1 While HHV-6 is often considered a potential etiologic agent in immunocompromised patients with encephalitis and other diseases, proof of a causal relationship is tenuous. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/ajt.14983
View details for PubMedID 29939480
Use of Alternative Agents for Prevention of Opportunistic Infections in Heart and Lung Transplant Recipients.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
View details for PubMedID 29771330
Micafungin Versus Posaconazole Prophylaxis in Acute Leukemia or Myelodysplastic Syndrome: A Randomized Study.
The Journal of infection
To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS).Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death). Time to failure and survival were calculated by Kaplan-Meier analysis.From March 2011 to May 2016, 113 patients who received at least 2 doses of prophylaxis were analyzed (58 patients randomized to micafungin and 55 to posaconazole). Prophylaxis failure occurred in 34.5% and 52.7% of patients on micafungin and posaconazole, respectively (P = 0.0118). The median number of days on prophylaxis was 16 [interquartile range (IQR) 12-20] for micafungin and 13 [IQR 6-16] for posaconazole (P = 0.01). Micafungin failures were largely due to antifungal treatment; posaconazole failures were mostly due to gastrointestinal intolerance or adverse effects. IFI incidence and survival were similar between study arms.Our data support micafungin as alternative antifungal prophylaxis in patients with AL and MDS.
View details for DOI 10.1016/j.jinf.2018.03.015
View details for PubMedID 29746955
- The Brief Case: Anaerobiospirillum succiniciproducens Bacteremia and Pyomyositis. Journal of clinical microbiology 2017; 55 (3): 665-669
- Closing the Brief Case: Anaerobiospirillum succiniciproducens Bacteremia and Pyomyositis. Journal of clinical microbiology 2017; 55 (3): 986-987
Toxoplasma Encephalitis in Atypical Hosts at an Academic Cancer Center.
Open forum infectious diseases
2016; 3 (2): ofw070-?
Toxoplasma encephalitis is a well recognized complication of acquired immune deficiency syndrome, solid organ transplantation, and allogeneic hematopoietic stem cell transplantation (HSCT). However, patients with hematologic malignancies not treated with allogeneic HSCT may also develop this condition, which requires high clinical suspicion and consideration for prophylactic therapy.
View details for DOI 10.1093/ofid/ofw070
View details for PubMedID 27096140
View details for PubMedCentralID PMC4834739