Altered phosphate metabolism in HIV-1-infected patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that has become a serious problem for HIV-1-infected patients. It has been proposed that disturbance of phosphate metabolism may represent a key feature of MS. Thus, we undertook the present study to investigate the relationship between phosphate levels and the presence of the characteristics of MS. METHODS: One hundred and twenty-one HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single-centre study. Kidney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. RESULTS: Univariate analysis showed that serum phosphate levels correlated negatively with systolic and diastolic blood pressure, glucose values, waist circumference, insulin, and triglycerides. Moreover, there was a positive relationship between phosphate and high-density lipoprotein (HDL) cholesterol. Multivariate analysis showed that insulin levels were correlated with serum phosphate concentration (r = - 0.24, p = 0.01). CONCLUSIONS: Our data show that HIV-1-infected patients with MS have lower phosphate levels.

Long-term efficacy and safety of TDM-assisted combination of voriconazole plus efavirenz in an AIDS patient with cryptococcosis and liver cirrhosis.

OBJECTIVE: To report the efficacy, tolerability, and pharmacokinetic effects of combined voriconazole and efavirenz treatment administered at therapeutic drug monitoring (TDM)-based adjusted doses to a patient with AIDS, cryptococcosis, and mild liver cirrhosis. CASE SUMMARY: A 40-year-old man with AIDS (hemophiliac, antiretroviral-naïve, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0), hepatitis C virus-related liver cirrhosis (Child-Pugh class A), and cryptococcal meningitis was failing standard antifungal therapies. He received an antifungal-antiretroviral combination treatment based on the association of voriconazole plus efavirenz. Doses of both drugs were serially adjusted based on their plasma concentrations, which were evaluated at steady-state of each dose combination at least once (week 3.1 or later) as full concentration-time profile (samples collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dose adjustment (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both administered orally). The patient showed prompt and stable suppression of cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no significant adverse events. DISCUSSION: Standard therapies for cryptococcosis in patients with AIDS are often not effective. Voriconazole, despite its promising anticryptococcal efficacy, is currently not approved for cryptococcosis therapy in the US and Europe, nor is it recommended for combination with efavirenz due to the significant pharmacokinetic interactions between the 2 compounds. Thus far, published studies regarding the effects of voriconazole in human cryptococcosis are scarce and none has described the clinical and pharmacokinetic outcomes of a voriconazole/efavirenz combination in patients with AIDS, either with or without liver cirrhosis. CONCLUSIONS: The combination of voriconazole and efavirenz at TDM-assisted doses may represent a valuable therapeutic option in AIDS patients with cryptococcosis and mild liver cirrhosis.

The correct approach to community-acquired pneumonia in immunocompetent adults: review of current guidelines.

Community-acquired pneumonia (CAP) often represents a clinical emergency requiring prompt and adequate antimicrobial treatment. The choice of antimicrobials, however, is difficult due to the variety of potential pathogens and to the spread of drug-resistance. Hence, a correct therapeutic approach should be based on the knowledge of the most frequently reported etiologies for the different clinical conditions, specific patient risk factors and the treatment setting (home, hospital, intensive or non intensive care unit) chosen accordingly. The awareness of the local drug-resistance epidemiology and individual patient characteristics, such as age, history of antibiotic treatments and related adverse events, underlying diseases, concurrent therapies and expected adherence to treatment should also be considered. Lastly, an adequate CAP management should address other issues, including therapy duration, monitoring of its efficacy and adverse effects, and supportive measures. The guidelines for CAP management aim to provide the physician with the necessary knowledge and criteria to assist him in these crucial decisions, and their adoption result in a significant reduction of mortality, frequency and length of hospitalization, and costs. Herein, the authors review and discuss some of the main current guidelines for CAP management, highlighting their differences and similarities.

Amoebic hepatic abscesses in an HIV-positive patient.

Herein we report the case of hepatic amoebic abscesses in an HIV-positive Italian seaman with a history of promiscuous heterosexual intercourse. In October 2004, the patient was hospitalized because of fever and recurring abdominal pain. Abdominal ultrasonography revealed six hepatic hypoechoid oval lesions with hyperechoid margins. Stool samples were negative for parasites and bacteria, and serology for Entamoeba histolytica was also negative. Therapy with meropenem plus levofloxacin was initiated. After a partial resolution of clinical symptoms and reduction of three hepatic lesions, the patient was again hospitalized in December 2004, because of recurring intense pain at the right hypochondrium and fever. At this time, one hepatic lesion at the sixth segment was enlarged, two lesions were unchanged, and the remaining three smaller abscesses were resolved. Serum antibodies for E. histolytica and amoebic antigens on the largest abscess drainage were positive; moreover, E. histolytica was also identified on drainage fluid with polymerase chain reaction (PCR). Therapy with metronidazole followed by paromomycin improved both symptoms and radiographic images. This case report suggests that in HIV-infected patients, invasive amoebiasis should be considered and atypical aspects, such as multiple hepatic lesions, delayed positivity of serology for E. histolytica, and possible bacterial superinfection should be evaluated.

Aeromonas sobria sepsis complicated by rhabdomyolysis in an HIV-positive patient: case report and evaluation of traits associated with bacterial virulence.

Human infection with Aeromonas species is uncommon and most often due to trauma with exposure to contaminated water or soil. A 43-year-old HIV- and hepatitis C virus (HCV)-infected male, after a two-week course of corticosteroid therapy for an autoimmune anemia, developed diarrhea, dermatologic manifestations and a multiple organ dysfunction syndrome, resulting in death. Although stool samples were repeatedly negative, two sets of blood cultures obtained during a single peak of fever yielded the post-mortem isolation of a Gram-negative, oxidase-positive, beta-hemolytic bacillus that was identified as Aeromonas sobria. Empiric antibiotic therapy was unsuccessful. Evaluation of the virulence-associated traits of the clinical isolate (adhesion, cytotoxicity activity, biofilm production) showed that the strain was a poor producer of recognized virulence factors, thereby indicating that the unfortunate coexistence of HIV infection, HCV-related liver cirrhosis and corticosteroids played a key role in the clinical course.