Sergio Carbonara

Epidemiological, clinical and therapeutic evaluation of the Italian cholera epidemic in 1994

In the period between October 18 and December 4, 1994, 12 indigenous cases of cholera were registered in the southern Italian region of Puglia, 10 of them were diagnosed in our Departments of Infectious Diseases. All patients were infected by consumption of raw fish or mussels. The patients had an elevated mean age and most were affected with systemic pathologies. The clinical course was mild and rarely complicated, although frequently the characteristic riziform diarrhoea was absent. In all patients V. cholerae serotype Ogawa biotype El Tor, was isolated; one patient was co-infected by Salmonella typhi. All strains showed resistance to cotrimoxazole and tetracycline. Nine of ten patients were treated with oral ciprofloxacin at 1 g/day for 10 days resulting in disappearance of the symptoms within a median of 36 hours and negative fecal cultures within a median of 24 hours. These data suggest that Italy is at high risk of infection imported from nearby nations. The resistance to commonly used antibiotics for treatment of cholera and the good response to ciprofloxacin suggest including fluoroquinolones among the drugs of first choice in geographical areas involved in the circulation of resistant strains of V. cholerae O1.

Disseminated Mycobacterium terrae Infection in a Patient with Advanced Human Immunodeficiency Virus Disease

Mycobacterium terrae has been rarely implicated in human disease and never in patients infected with human immunodeficiency virus (HIV). We describe an HIV-infected patient with disseminated infection by M. terrae with pulmonary and cutaneous clinical manifestations. M. terrae was isolated from both sputum and urine, and identified by both conventional tests and high-performance liquid chromatography. Clinical and microbiological characteristics of this case are compared with those reported in the literature.

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. Conlusions 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.

Polymerase chain reaction for non-invasive diagnosis of brain mass lesions caused by Mycobacterium tuberculosis: Report of five cases in human immunodeficiency virus-positive subjects

To investigate whether the polymerase chain reaction (PCR) on the IS6110 sequence of Mycobacterium tuberculosis could permit the early and non-invasive diagnosis of tuberculous brain lesions without meningeal involvement in acquired immunodeficiency virus patients, we examined retrospective cerebrospinal fluid (CSF) samples from five patients diagnosed as having cerebral lesions caused by M. tuberculosis. M. tuberculosis deoxyribonucleic acid was detected in CSF samples obtained from each of the patients studied, but in none of the controls. The PCR results coincided with M. tuberculosis isolation from CSF in two patients. In an additional two subjects, culture for M. tuberculosis on CSF was negative, and the diagnosis of central nervous system tuberculosis was achieved by response to specific therapy. In the last patient the PCR result on CSF was confirmed by isolation of M. tuberculosis from brain biopsy. Interestingly, in this patient the CSF did not yield M. tuberculosis isolation when cultured. The data show the value of PCR as a potentially useful approach for the early and rapid diagnosis of cerebral tuberculosis even without meningitis.

Impact of previous ART and of ART initiation on outcome of HIV-associated tuberculosis.

Background. Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. Methods. A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. Results. Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0–16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. Conclusions. ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.

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.

Drug-resistant tuberculosis in HIV-infected persons: Italy 1999-2000.

Background:Patients with HIV infection may be a valuable target for assessing the impact of drug-resistant tuberculosis (TB).Patients and Methods:An observational, prospective study was conducted in 96 infectious disease hospital units in Italy during 1999–2000. A total of 140 HIV-infected patients with diagnosis of TB and with an isolate tested for drug susceptibility entered the analysis. Drug resistance (DR) was defined as resistance to either isoniazid (INH) or rifampin (RIF), while multidrug resistance (MDR) was defined as resistance to INH and RIF.Results:A total of 117 (83.6%) episodes of TB were classified as new cases and 23 (16.4%) as previously treated cases. Prevalence of resistance to INH or RIF was 12.8% and 4.3% among new cases, and 17.4% and 26.1% among previously treated cases, respectively. Prevalence rates of DR and MDR were 14.5% and 2.6% among new cases and 30.4% and 12.5% among previously treated cases, respectively. No statistically significant risk factors associated with DR or MDR TB emerged in this analysis.Conclusion:High prevalence rates of DR and MDR are present among HIV-infected TB patients in Italy, in particular among previously treated cases.

Targeting Candidates for Directly Administered Highly Active Antiretroviral Therapy: Benefits Observed in HIV-Infected Injecting Drug Users in Residential Drug-Rehabilitation Facilities

The purpose of this study was to evaluate retrospectively the potential benefits of directly administered antiretroviral therapy (DAART) in HIV-infected former injecting drug users (ex-IDUs) admitted to residential drug rehabilitation facilities. We compared 106 of these patients consecutively admitted in 12 communities where DAART was administered (DAART group) to two matched control groups of ex-IDUs undergoing self-administered ART: 106 subjects in other 10 communities (SAT group) and 106 outpatients at hospital infectious-disease wards where community patients were referred after discharge (OUT group). We estimated the proportion of patients with high adherence and the hazard ratio (HR) of 20% or more increase in the CD4(+) cell count and of reaching an undetectable viral load. The proportion of patients with high adherence to treatment was highest in the DAART group. The probability of 20% or more increase in the CD4(+) cell count was significantly lower in the two control groups versus the DAART group (SAT group HR=0.32; OUT group HR=0.43). The HR of observing an undetectable HIV-RNA level versus DAART was significantly lower in the OUT group (HR: 0.71; 95% confidence interval [CI]: 0.52-0.97) but did not reach statistical significance for the SAT group (HR: 0.99; 95% CI: 0.74-1.33). Our findings after a 24-month follow-up, suggest that DAART in HIV-infected patients of drug-rehabilitation communities improves adherence, immunologic, and virologic outcome toward free outpatients. Even if our retrospective 36-month data do not show a prolonged viral suppression in these patients, DAART may be considered a valuable therapeutic and educational strategy in this particular target group.

Chlamydia trachomatis and Mycobacterium tuberculosis lung infection in an HIV-positive homosexual man.

A 31-year-old homosexual man, who was human immunodeficiency virus (HIV)-positive was admitted for fever and cough. Chest computed tomography (CT) revealed the presence of diffuse interstitial reticular nodulation, and brain nuclear magnetic resonance imaging showed the presence of nodular frontal lesions. Microscopic examination of sputum and other body fluids showed the presence of acid-fast bacilli and culture-only growth Mycobacterium tuberculosis. Serology for respiratory tract pathogens was negative except for Chlamydia. An antibody titer in the immunoglobulin G (IgG) class of 1:64 for Chlamydia pneumoniae and, unexpectedly, an antibody titer of 1:1024 for C. trachomatis were found. The patient was successfully treated with antituberculosis agents, and clarithromycin, for presumptive chlamydial infection.

Management of HCV infection in the penitentiary setting in the direct-acting antivirals era: practical recommendations from an expert panel

BackgroundThe prevalence of HCV infection is higher among prisoners than in the general population. The introduction of HCV direct-acting antivirals (DAA) holds the potential to improve clinical outcomes also in inmates. However, treatment of hepatitis C in inmates has to face several clinical and logistical issues which are peculiar of prison environment. Recommendations on the management of HCV infection specific for the penitentiary setting in the DAA era remain scant. The Italian Society for Penitentiary Medicine and Healthcare has, therefore, issued these recommendations, to provide clinicians with a guide for the comprehensive management of HCV infection in the restriction setting, taking into account its peculiar characteristics.ResultsDedicated diagnostic and treatment procedures should be established in each prison. In particular, the use of DAAs appears crucial to provide patients with an effective therapeutic option, able to overcome the limitations of IFN-based regimens with a short period of treatment. DAA treatment should be initiated as soon as possible in all eligible subjects with the aim to cure the patient, as well as to limit the transmission of HCV infection both inside the penitentiary system and to the free community, once the inmates ends his/her release. Importantly, efforts should be made to open a discussion with regulatory bodies, to define specific regulations aimed to guarantee wide access to effective therapies of all eligible patients, to optimize the management of and the adherence to the HCV treatment, and to ensure the therapeutic continuity after discharge from prison.