Aneela Majeed

An update on emerging therapies for urinary tract infections

ABSTRACT Introduction: Urinary tract infections (UTIs) are the most common healthcare-acquired infections, and are associated with high morbidity and mortality. Worldwide use of antibiotics has led to a significant rise in resistant uropathogens emanating from both hospitals and communities. The huge concern of multidrug resistance (MDR) has led the Food and Drug Administration (FDA) to encourage drug companies to invest in the development of new antibiotics. Area covered: In this review we summarized data on already approved antibiotics, and selected emerging therapies that are currently in phase II and III trials with emphasis on complicated urinary tract infections (cUTIs). We performed our search using PubMed, ClinicalTrials.gov, Google Scholar and Pharmaprojects. Expert opinion: Efficacious antimicrobials are needed to overcome MDR organisms. There are several dugs in initial and later stages of development, but most of them lack full spectrum of activity against some Gram-negative organisms, particularly against MDR Pseudomonas aeruginosa. Better understanding of the pathogenesis of UTI and genetic engineering of pathogens can provide new drugs to combat resistance in the future.

First case of acute granulomatous interstitial nephritis with immune reconstitution inflammatory syndrome in a patient with HIV coinfected with disseminated Mycobacterium kansasii

Restoration of immune response by highly active antiretroviral therapy (HAART) effectively improved the overall prognosis of HIV infection. However, 25%–31.7% of patients experience paradoxical worsening of pre-existing infections or unmasking of subclinical infections after starting HAART therapy, which is termed as immune reconstitution inflammatory syndrome (IRIS). Acute granulomatous interstitial nephritis as a consequence of IRIS has never been reported with Mycobacteriumkansasiicoinfection. Here, we describe an HIV/AIDS patient coinfected with disseminated M. kansasii infection, who presented with acute kidney injury 4.5 months after initiation of HAART. The diagnostic workup revealed IRIS was the cause of acute kidney injury. Short-term course of prednisone (1 mg/kg/day) along with antimycobacterial and HAART regimen achieved significant improvement.

Intractable cerebral Nocardia mexicana in a GvHD patient successfully treated with linezolid

Intractable cerebral Nocardia mexicana in a GvHD patient successfully treated with linezolid

A 20-year experience with nocardiosis in solid organ transplant (SOT) recipients in the Southwestern United States: A single-center study

Nocardiosis is a life‐threatening opportunistic infection. Solid organ transplant (SOT) recipients are at higher risk (incidence 0.04%‐3.5%) of developing nocardiosis. Rate of nocardiosis in the Southwestern US may be high due to environmental factors.

Management of Recurrent Clostridium difficile Infection During Intensive Chemotherapy and Stem Cell Transplantation for Leukemia: Case with Literature Review

Immunocompromised patients undergoing chemotherapy for hematologic malignancy and hematopoietic stem cell transplant (HSCT) recipients are at increased risk of Clostridium difficile (C. difficile) infection (CDI). The recurrence of infection and its associated morbidity and mortality are due to multiple risk factors. Diarrhea is common in HSCT recipients, but the diagnosis of diarrhea caused by CDI is a therapeutic challenge due to frequent Clostridium difficile colonization with diarrhea secondary to non-infectious causes. The high recurrence rate is a significant challenge in the treatment of immunocompromised patients. Close monitoring of the patients, timely diagnosis, preventive measures, treatment with antibiotics, and the removal of offending agents can help in the management and cure of the disease. We review the literature on management and describe a patient with acute lymphoblastic leukemia (ALL) with multiple recurrences of CDI during leukemia therapy and allogeneic stem cell transplantation for leukemia.

Prophylaxis for Hepatitis B Virus Reactivation after Allogeneic Stem Cell Transplantation in the Era of Drug Resistance and Newer Antivirals: A Systematic Review and Meta-Analysis

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

Invasive Mucormycosis Induced Pneumopericardium: A Rare Cause of Pneumopericardium in an Immunocompromised Patient

Mucor and Rhizopus cause life-threatening infections primarily involving the lungs and sinuses, which disseminate very rapidly by necrosis and infarction of the contiguous tissues. We present a case of a 64-year-old African American posttransplant patient who presented with a productive cough and weight loss. He had a past surgical history of renal transplant for renal cell carcinoma and was on dual immunosuppressive therapy, that is, mycophenolate and tacrolimus. During his hospital stay, he developed a pneumopericardium due to the direct extension of a lung lesion. The diagnosis was made by radiological imaging and PCR result which was consistent with Mucor species. He was treated with antifungal therapy. The purpose of this report is to highlight the unusual association of mucormycosis with pneumopericardium.

Hodgkin Lymphoma Mimicking Osteomyelitis

Hodgkin lymphoma with symptomatic osseous involvement can have a similar presentation to osteomyelitis. Common findings in symptoms, laboratory workup, and imaging can make it very difficult to distinguish between the two diseases. Excisional biopsy should be pursued if fine-needle biopsy is equivocal and suspicion of lymphoma is high. We report a case of a 40-year-old man who presented with a history of marine animal sting on his neck and later developed erythema in the area, chest pain, constitutional symptoms, adenopathy, and imaging classic for sternal osteomyelitis. Fortunately, initial biopsy prompted the possibility of lymphoma, and further workup was initiated, which confirmed Hodgkin lymphoma. This case is a good reminder that malignancies and infections can share many common features, and keeping a broad differential diagnosis can be lifesaving. Proper staging and risk stratification of Hodgkin lymphoma help determine the optimal treatment.

First reported case of disseminated Nocardia kroppenstedtii sp nov. infection presenting with brain abscess and endocarditis in an immunocompromised patient with mantle cell lymphoma: challenges in diagnosis and treatment

A 72-year-old man with a history of blastoid variant stage IV relapsed refractory mantle cell lymphoma presented with new central nervous system (CNS) symptoms. Brain imaging was positive for rim-enhancing lesions along with a mitral valve mass on the echocardiogram. It was a challenge to establish the exact aetiology of these lesions in this patient. He was empirically treated with chemotherapy on the presumption that the brain lesions were secondary to progressive malignancy. However, brain biopsy was negative for malignancy and blood cultures were found positive for Nocardia kroppenstedtii sp nov. He subsequently improved with antibiotic therapy. Disseminated Nocardia can present with multiorgan involvement. Clinical and microbiological diagnosis can be challenging. Antimicrobial treatment-related side effects require close monitoring, and dosage changes or therapy adjustments may be necessary.

A 30-year delayed presentation of disseminated histoplasmosis in a heart transplant recipient: Diagnostic challenges in a non-endemic area

A 70-year-old man with history of heart transplant performed in 1986, presented with altered mental status. CT scan of brain showed ring-enhancing lesions, raising suspicion for metastatic malignancy. Work-up revealed bilateral adrenal masses, biopsy showed granulomatous changes consistent with histoplasmosis. The possibility of histoplasmosis was less likely as the patient had no prior history of symptomatic disease and had lived in the endemic area 30 years prior to presentation. Brain biopsy confirmed central nervous system involvement. Amphotericin B was initiated for disseminated disease but his hospital course was complicated by renal failure and new liver hypodensities on follow-up imaging. Acute progressive disseminated histoplasmosis can manifest after decades of initial exposure and should always be in differential diagnosis even in non-endemic areas for prompt diagnosis and better clinical outcome.