Infections in Heart and Lung Transplant Recipients.

Patients undergoing thoracic organ transplantation procedures involving the heart or lung are at increased risk for developing a wide variety of infections due to their underlying immunosuppression and/or other factors. Lung transplant recipients are at high risk for developing infections caused by bacteria, viruses, and opportunistic fungi, whereas heart transplant recipients are at risk for developing infections caused by these same microorganisms, as well as parasitic infections, including toxoplasmosis and New World trypanosomiasis. This review will highlight the various infections that thoracic organ transplant recipients may develop following their procedures.

Culture-negative bivalvular endocarditis with myocardial destruction in a patient with systemic lupus erythematosus: a case report.

Culture-negative endocarditis has long been associated with systemic lupus erythematosus, but is usually asymptomatic or involves a single valve. We present a patient with destructive culture-negative endocarditis that remains without a microbial etiology despite an exhaustive workup using advanced diagnostic techniques in a patient with systemic lupus erythematosus.

Antiretroviral therapy 2010 update: current practices and controversies.

Over the past four years, significant advances have been made in human immunodeficiency virus (HIV) therapy. In addition to the release of two new classes of antiretrovirals, our understanding of the older antiretrovirals continues to improve. Multiple combination pills have been brought to market, simplifying the regimens for patient ease. New controversies have arisen, notably the role of antiretrovirals in the chronic inflammatory state that HIV infection produces, which may lead to excess cardiac, renal, and hepatic mortality. The optimum time to initiate antiretroviral therapy remains unknown but clinicians are treating HIV infection earlier in its course. In this article, we review these and other new issues relating to the care of the HIV patient.

Resolution of persistent Pediococcus bacteremia with daptomycin treatment: case report and review of the literature.

A case of bacteremia caused by Pediococcus acidilactici occurring in a patient with metastatic adenocarcinoma of the gallbladder is described. The bacteremia persisted despite an antimicrobial regimen of vancomycin, ciprofloxacin, metronidazole, and caspofungin. Within 36 h of switching the vancomycin to daptomycin (6 mg/kg per day), the bacteremia resolved and the patient improved clinically. Previous reports of human pediococcal infection are also reviewed.

Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis.

BACKGROUND: Invasive candidiasis is an important cause of morbidity and mortality among patients with health care-associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of invasive candidiasis. METHODS: This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of invasive candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. RESULTS: A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic invasive candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms. CONCLUSIONS: Dosages of micafungin 100 mg daily and 150 mg daily were noninferior to a standard dosage of caspofungin for the treatment of candidemia and other forms of invasive candidiasis.

Inhibition of HIV type 1 replication in CD4+ and CD14+ cells purified from HIV type 1-infected individuals by the 2-5A agonist immunomodulator, 2-5A(N6B).

Two major interferon (IFN)-mediated antiviral defense enzymes are double-stranded (ds)RNA-dependent 2',5'-oligoadenylate (2-5A) synthetase (2-5OAS) and p68 kinase (PKR). When activated by dsRNA, 2-5OAS synthesizes 2-5A, which binds to and activates RNase L. Activated RNase L hydrolyzes single-stranded viral RNA, thereby inhibiting viral protein synthesis. HIV-1 inhibits the IFN-mediated intracellular antiviral pathways. We have reported the synthesis and characterization of a nuclease-resistant 2-5A agonist (2-5A(N6B)) that overcomes the HIV-1 induced blockades by restoring the 2-5OAS/RNase L antiviral pathway (Homan JW, et al., J Acquir Immune Defic Syndr 2002;30:9-20). The objective of this study was to test the effect of 2-5A(N6B) on chronically infected CD4(+) T lymphocytes and CD14(+) monocytes derived from HIV-1-seropositive individuals. Wild-type HIV-1 replication was effectively inhibited by 2-5A(N6B) in CD4(+) T lymphocytes and CD14(+) monocytes purified from HIV-1 seropositive individuals (n = 18) compared to untreated cells. We also assessed the cytotoxicity of 2-5A(N6B) and report that 2-5A(N6B) exerts its anti-HIV-1 activity with no evidence of cytotoxicity (IC(90) > 100,000 nM). Furthermore, 2-5A(N6B) did not alter the cellular RNA profile, affect CCR5 or CXCR4 coreceptor expression, or activate caspase-dependent apoptosis. Evidence is also provided to show that 2-5A(N6B), and naturally occurring 2-5A(4), act as ligands to activate human Toll-like receptor 4. These results indicate that the 2-5A agonist 2-5A(N6B) has the potential to enhance host cell innate and acquired immune defense mechanisms against HIV-1 infection.

Antiretroviral therapy 2006: pharmacology, applications, and special situations.

As we approach the completion of the first 25 years of the human immunodeficiency virus (HIV) epidemic, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity. There are twenty currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed. We have included a section addressing common comorbid conditions including hepatitis B and C along with tuberculosis.

Potential clindamycin resistance in clindamycin-susceptible, erythromycin-resistant Staphylococcus aureus: report of a clinical failure.

The erm gene product confers clindamycin resistance on Staphylococcus aureus. We report a clindamycin clinical failure where resistance developed on therapy in a D-test-positive strain. D tests of 91 clindamycin-susceptible, erythromycin-resistant S. aureus isolates showed that 68% of methicillin-susceptible and 12.3% of methicillin-resistant S. aureus strains were D-test positive.

Cladophialophora bantiana brain abscess in a solid-organ transplant recipient: case report and review of the literature.

Cerebral phaeohyphomycosis caused by Cladophialophora bantiana is a rare disease. We describe a heart and bilateral lung transplant recipient who was unsuccessfully treated for a C. bantiana brain abscess. This report compares the present case to those of other solid-organ transplant recipients with the same infection and to those of patients who did not receive transplants.

Esophageal bacteria and Barrett's esophagus: a preliminary report.

The objective of this study was to investigate if esophageal bacteria are associated with Barrett's esophagus (BE). This study was comprised of a retrospective (Part 1) and a subsequent prospective (Part 2) study. In Part 1, Gram stains were performed on esophageal biopsy specimens obtained in 47 patients. Bacteria were quantitated from 0 to 4. In Part 2, Gram stains and cultured bacterial counts of esophageal biopsies were obtained in 18 GERD patients (9 with BE and 9 without BE). Part 1 results were as follows. Bacteria were found in 37 of 47 esophageal biopsies. Quantitative bacterial stain scores for BE (2.5 +/- 0.2) were higher than for non-BE (1.5 +/- 0.3; P = 0.02). The quantitative bacterial stain scores correlated with increasing severity of dysplasia (r = 0.37, P = 0.028). In Part 2, bacteria were found in 8 of 18 esophageal biopsies by Gram stain (6 of 9 patients with BE vs. 2 of 9 non-BE). The distal esophageal bacterial stain scores in BE patients (1.6 +/- 0.5) were higher than in those without BE (0.4 +/- 0.3; P = 0.07). Patients on proton pump inhibitors tended to have higher bacterial stain scores (1.2 +/- 0.4) than patients who were not (0.7 +/- 0.3; P = 0.45). Bacterial colony counts were similar in patients with BE compared to those without BE. In conclusion, bacteria in esophageal biopsies were detected more often in BE than non-BE. Increasing bacterial stain scores were associated with metaplasia and increasing dysplasia. Esophageal bacteria, possibly related to stasis or gastric acid suppression therapy, may play a role in the pathogenesis of BE and dysplasia.

AIDS related opportunistic infections, going but not gone.

It is now more than two decades since the AIDS epidemic began with a cluster of Pneumocystis carinii pneumonia (PCP) in a community of homosexual men. Since then, many other infections have been characterized as opportunistic infections secondary to HIV infection. These include, but are not limited to, infections with Toxoplasma gondii, Cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and Cryptococcus neoformans. Over the last two decades, there have been dramatic improvements in diagnosis, prevention and treatment of all these infections. As a result, in North America and Western Europe the rates of opportunistic infections secondary to AIDS have decreased substantially. We will review these common opportunistic infections below.