Sandro Cinti

HIV Protease Inhibitors: Advances in Therapy and Adverse Reactions, Including Metabolic Complications

Protease inhibitors (PIs) effectively inhibit replication of the human immunodeficiency virus (HIV), and reduce mortality and prolong survival in patients with HIV infection. Newer PIs saquinavir (soft gelatin capsule) and amprenavir, as well as other PIs, may be effective when administered twice/day. Adverse reactions may occur, as well as metabolic complications and interactions between PIs and other drugs, including other PIs. The strategy of combining PIs is based on specific pharmacologic interactions among the agents.

Recurrence of Mycobacterium avium Infection in Patients Receiving Highly Active Antiretroviral Therapy and Antimycobacterial Agents

The known effects of highly active antiretroviral therapy (HAART) on opportunistic infections (OIs) range from immune restoration disease to remission of specific OIs. In the present study, Mycobacterium avium complex infection recurred in 3 patients receiving antimycobacterial therapy and HAART. At the time of the initial M. avium infection, the mean CD4 cell count was 22.3 cells/mm3, and the HIV viral load was 181,133 copies/mL. Relapse occurred a mean of 14. 3 months after the first episode; the mean follow-up CD4 cell count was 89/mm3 (mean elevation of 66 cells/mm3), and the HIV viral load was <400 copies/mL in each patient. M. avium was isolated from blood (1 patient), blood and lymph node (1), and small-bowel tissue (1). M. avium infection may recur as a generalized or focal disease in those who are receiving antimycobacterial agents but whose HAART-associated CD4 cell recovery, although significant, is not optimal.

Case Report. Recurrence of increased intracranial pressure with antiretroviral therapy in an AIDS patient with cryptococcal meningitis

Summary.  We present the case of an AIDS patient with cryptococcal meningitis who, after an excellent clinical and mycological response to antifungal therapy, developed an exacerbation of signs and symptoms, including elevated intracranial pressure and an increase in cerebrospinal fluid cryptococcal antigen and white blood cells, following the initiation of highly active antiretroviral therapy (HAART). Cultures yielded no growth and the patient responded to repeated lumbar punctures without changing or intensifying antifungal therapy. To our knowledge, this is the first report of symptomatic elevated intracranial pressure occurring during HAART‐related immune recovery in a patient with cryptococcal meningitis. Exacerbation of symptoms does not necessarily reflect mycological failure that requires a change in antifungal therapy, but may relate to acutely increased intracranial pressure that will respond to simple measures, such as repeated lumbar punctures.

Bartonella henselae infections in solid organ transplant recipients: report of 5 cases and review of the literature.

Bartonella henselae is the causative agent of cat scratch disease and bacillary angiomatosis-peliosis. The spectrum of disease, diagnosis, and management of B. henselae infection in solid organ transplant recipients has not been well characterized. We identified 29 cases of solid organ transplant recipients who had Bartonella infection, 24 by a review of the English-language literature and 5 from our institution. Localized cat scratch disease was found in 8 patients (28%), and disseminated infection was found in 21 patients (72%). The mean time after transplantation to development of Bartonella infection among those with cat scratch disease was 5.6 ± 5.3 years, and among those with disseminated infection was 2.7 ± 2.4 years. Prominent clinical features included cat exposure in 26 patients (90%), fever in 27 patients (93%), lymphadenopathy in 12 patients (41%), and skin lesions in 7 patients (24%). Methods used in establishing the diagnosis of Bartonella infection included culture, polymerase chain reaction (PCR) assay, serologic assays, and histopathologic examination. Culture was positive in 2 of only 4 patients in whom this was performed, and PCR was positive in 12 of 14 patients (86%) in whom this test was performed. Serologic assays were positive in all 23 patients who were tested. Histopathologic examination of tissues in all 8 patients who had cat scratch disease revealed granulomatous inflammation in 4 (50%) and bacillary angiomatosis-peliosis in 2 (25%). Among the 15 patients who had disseminated infection and who had tissue examined, 8 (53%) had only granulomatous inflammation, 4 had only bacillary angiomatosis-peliosis (27%), and 2 had both granulomas and bacillary angiomatosis-peliosis (13%). A positive Warthin-Starry or Steiner stain was noted in 12 of 19 patients (63%) who had 1 of these stains performed. All 8 patients with cat scratch disease and 19 of 21 patients with disseminated bartonellosis were cured with antimicrobial therapy. Two patients, both of whom had endocarditis, died. Among solid organ transplant recipients, infection with B. henselae is uncommon and has diverse disease manifestations including disseminated disease. Persistent fevers or lymphadenopathy in a transplant recipient who has been exposed to cats should prompt clinicians to maintain a high index of suspicion for B. henselae infection. Identifying B. henselae as the causative organism often requires multiple diagnostic studies. Once the diagnosis is established, most solid organ transplant recipients respond appropriately to antimicrobial treatment. AbbreviationsAIDS = acquired immunodeficiency syndromeALT = alanine aminotransferaseAST = aspartate aminotransferaseCMV = cytomegalovirusCT = computed tomographyEBV = Epstein-Barr virusERCP = endoscopic retrograde pancreaticocholangiogramFDG = 18F-fluorodeoxyglucoseHHV-6 = human herpesvirus-6HIV = human immunodeficiency virusHSV = herpes simplex virusIFA = immunofluorescence assayIgG = immunoglobulin GIgM = immunoglobulin MMRI = magnetic resonance imagingPCR = polymerase chain reactionPET = positron emission tomographyWBC = white blood cell count

Pandemic influenza: are we ready?

An influenza pandemic is inevitable, and the H5N1 avian influenza outbreak in Southeast Asia has heightened concern that a disaster is imminent. Pandemic preparations are beginning around the world, and it is important for first responders, particularly disaster management personnel, to understand the difference between pandemic and epidemic influenza preparedness. This article will focus on distinguishing between an influenza epidemic and an influenza pandemic and, in light of these distinctions, how to manage the next pandemic with limited resources, particularly the absence of vaccine.

Neutrophils from AIDS Patients Treated with Granulocyte Colony-Stimulating Factor Demonstrate Enhanced Killing of Mycobacterium avium

Neutrophils isolated from AIDS patients have demonstrated improved growth inhibition of Mycobacterium avium when incubated with exogenous granulocyte colony-stimulating factor (G-CSF). In this clinical study, 30 AIDS patients without M. avium infection were randomized to receive 5 days of treatment with rifabutin, G-CSF, or both agents. The M. avium killing capacity of neutrophils harvested from each patient before intervention, during (day 4), and after therapy (day 7) was assessed. The mean change in human immunodeficiency virus load in the group receiving G-CSF alone was -0.07 log of viral RNA. There was a 90% reduction in M. avium growth after therapy for patients treated with G-CSF alone (P=.01), 59% for patients treated with both agents (P=.06), and 11% for patients treated with rifabutin alone (P=.84). Thus, neutrophils isolated from AIDS patients treated with G-CSF demonstrated a significant enhancement of killing of M. avium; there was no notable effect on virus load.

An elderly patient with fluoroquinolone-associated achilles tendinitis.

BACKGROUND Due to their broad-spectrum activity and oral bioavailability, fluoroquinolone antibiotics are commonly prescribed to adults aged >60 years for many common community-acquired infections. The association between fluoroquinolone use and Achilles tendinitis is well established but sometimes missed in clinical practice. Older patients and patients with renal dysfunction are at particularly increased risk for this complication. CASE SUMMARY We present a case of Achilles tendinitis in a 77-year-old patient with renal dysfunction and a urinary tract infection (UTI) treated with ciprofloxacin 250 mg PO QD. Tendinitis developed within several days of the start of treatment and improved within 2 days of treatment cessation, without the need for intervention. The likelihood of ciprofloxacin having caused this reaction was probable (Naranjo score, 7). Early diagnosis and treatment cessation might have prevented tendon rupture, and the tendinitis resolved completely with subsequent physical therapy. CONCLUSION Based on this outcome in this patient with UTI, fluoroquinolones should be used with caution, particularly in patients with risk factors predisposing to tendinitis, including advanced age and renal dysfunction.

Killing of Mycobacterium avium by Neutrophils and Monocytes from AIDS Patients Treated with Recombinant Granulocyte-Macrophage Colony-Stimulating Factor

In this study, 30 AIDS patients without Mycobacterium avium infection were randomized to receive treatment with azithromycin (1200 mg), granulocyte-monocyte colony-stimulating factor (GM-CSF; 250 microg/m2/day for 5 days), or both agents. The M. avium killing capacity of neutrophils and monocytes harvested from each patient before intervention and during (day 4), and after therapy (day 8) was assessed. The mean virus load change in the groups receiving GM-CSF was +0.14 log human immunodeficiency virus RNA. After GM-CSF therapy, neither neutrophils nor monocytes could significantly reduce M. avium growth (P=.96 and.31, respectively). Bone pain, myalgia, presyncope, or fever occurred in 55% of patients receiving GM-CSF. Thus, the GM-CSF regimen used in this study did not affect virus load, frequently caused adverse reactions, and did not improve the M. avium killing capacity of neutrophils and monocytes. Future studies using a different GM-CSF regimen are indicated.

Pandemic Influenza Planning in Nursing Homes: Are We Prepared?

Avian influenza or Influenza A (H5N1) is caused by a viral strain that occurs naturally in wild birds, but to which humans are immunologically naïve. If an influenza pandemic occurs, it is expected to have dire consequences, including millions of deaths, social disruption, and enormous economic consequences. The Department of Health and Human Resources plan, released in November 2005, clearly affirms the threat of a pandemic. Anticipating a disruption in many factions of society, every segment of the healthcare industry, including nursing homes, will be affected and will need to be self‐sufficient. Disruption of vaccine distribution during the seasonal influenza vaccine shortage during the 2004/05 influenza season is but one example of erratic emergency planning. Nursing homes will have to make vital decisions and provide care to older adults who will not be on the initial priority list for vaccine. At the same time, nursing homes will face an anticipated shortage of antiviral medications and be expected to provide surge capacity for overwhelmed hospitals. This article provides an overview of current recommendations for pandemic preparedness and the potential effect of a pandemic on the nursing home industry. It highlights the need for collaborative planning and dialogue between nursing homes and various stakeholders already heavily invested in pandemic preparedness.

Developing a fully online course for senior medical students

Abstract In 2002 the University of Michigan Medical School created a one-month course in advanced medical therapeutics (AMT). All senior medical students were required to complete the course. To provide some flexibility for students who were interviewing for residency positions the AMT course was created using a distance-learning model, and in the 2008–2009 academic year it was offered in a fully online format. The components of the course are weekly case-based modules, a weekly online seminar, quizzes based on modules and seminars, and a research project based on a therapeutic question. The paper discusses the development and components of the AMT course, a survey of fourth-year medical students who participated in the course between 2007 and 2010, and how the course evolved over three years.