Benedetto Caroleo

Chronic wound infections: the role of Pseudomonas aeruginosa and Staphylococcus aureus

Chronic leg ulcers affect 1–2% of the general population and are related to increased morbidity and health costs. Staphylococcus aureus and Pseudomonas aeruginosa are the most common bacteria isolated from chronic wounds. They can express virulence factors and surface proteins affecting wound healing. The co-infection of S. aureus and P. aeruginosa is more virulent than single infection. In particular, S. aureus and P. aeruginosa have both intrinsic and acquired antibiotic resistance, making clinical management of infection a real challenge, particularly in patients with comorbidity. Therefore, a correct and prompt diagnosis of chronic wound infection requires a detailed knowledge of skin bacterial flora. This is a necessary prerequisite for tailored pharmacological treatment, improving symptoms, and reducing side effects and antibiotic resistance.

Hepatitis C virus infection in an endemic area of Southern Italy 14 years later: Evidence for a vanishing infection

BACKGROUND In a 1996 survey, prevalence of hepatitis C virus antibodies (anti-HCV) in a southern Italian town was 12.6%. AIMS To identify changes in the epidemiology of hepatitis C virus (HCV) infection. METHODS Anti-HCV, HCV-RNA (PCR, detection limit 15 IU/mL), HCV genotype (Innolipa). Were performed in a random 1:4 systematic sample of the general population. Multiple logistic regression analysis was used to estimate factors independently associated with the likelihood of anti-HCV positivity. RESULTS Of 1012 subjects, 58 (5.7%) were anti-HCV-positive, compared to 12.6% 14 years earlier. Prevalence was 0.4% in individuals <30 years old and 31.8% in those ≥ 70 years old. Among 139 HCV-negative in 1996 re-sampled in 2010, only one had seroconverted (incidence: 0.05 × 100 persons/year). Alanine transaminase levels were elevated in 8 (13.8%). HCV-RNA was detected by PCR in 46.5% anti-HCV-positive subjects. In 2010 59% were genotype 2-infected, in 1996 50.7% genotype 1-infected. Previous use of non-disposable glass syringes was a strong independent predictor (OR 3.2; CI 95%=1.4-7.3). CONCLUSION Epidemiology of HCV infection in an endemic area of south Italy has changed over 14 years, now largely confined to the oldest age group; this seems to be due to the disappearance of its past main mode of transmission, namely the use of glass syringes.

Eleven-Year Distribution Pattern of Hepatitis C Virus in Southern Italy

Analysis of the Hepatitis C Virus (HCV) genotype spread in a particular area has a crucial impact on public health. In this study, we update information on the distribution of HCV genotypes, by evaluating a hospital-based cohort of 2,153 chronic hepatitis C patients, collected prospectively among subjects attending University Hospital of Catanzaro, within an area of Southern Italy. We assessed the rates (%) of HCV genotypes during two consecutive periods, from 2001 to 2005 and from 2006 to 2011, according to age and gender. Considering overall observation time, subtype 1b was predominant followed by subtypes 2a/2c, genotype 3 and 4. Statistical evaluation of the age of HCV patients stratified by genotypes, revealed a slight but significant increase in the median age of 1b, 2a/2c and 3 HCV genotype-infected subjects, during the 2006–2011 period, whilst genotype 4 patients exhibited a decrease in the median age during the same period studied. Moreover genotype 4 increased between 2002 and 2003 as well as between 2010 and 2011. Due to the peculiar diagnostic/clinical/therapeutic features of HCV-4, our findings warrant a deeper investigation to better control infections caused by such genotype.

The impact of a vaccination campaign against hepatitis B on the further decrease of hepatitis B virus infection in a southern Italian town over 14 years

BACKGROUND Hepatitis B virus infection has decreased in Italy. The aims of this study were to identify changes, if any, in the epidemiological pattern of HBV infection in a southern Italian town first surveyed in 1996 and to assess the effectiveness of vaccination campaign against hepatitis B. METHODS In 2010, subjects were selected from the census by a systematic 1:4 random sampling procedure. Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc) were detected by ELISA. Associations (odds ratios) linking exposure to hepatitis B virus infection to potential risk factors were estimated by univariate and multivariate analyses. RESULTS Of the 1100 eligible subjects, 1020 (92.0%) agreed to participate. The prevalences of HBsAg (0.6%) and anti-HBc (15.2%) were significantly lower than in 1996 (0.8% and 21.5%) (p<0.01). No subject below 30 years of age (those that had been targeted for compulsory immunization) had been exposed to HBV infection. At multiple logistic regression analysis, age>45 years (OR=9.8; 95% CI=5.1-18.7) and past use of glass syringes (OR=1.9; 95% CI=1.2-3.1) independently predicted the likelihood of anti-HBc positivity. CONCLUSIONS These results, albeit obtained in a small town and thus not generalizable, confirm the continuous decreasing trend of HBV infection and demonstrate the effectiveness of the Italian hepatitis B vaccination program.

Cutaneous Ulceration Induced by Interferon Alfa

1.32 × 103/mm3, platelets 124 × 103/mm3, serum creatinine 0.6 mg/dL, and albumin 4.5 g/dL. Creatinine clearance was 79 mL/min. Treatment with methotrexate had been initiated 2 years earlier (4 mg/wk, total cumulative dose 416 mg). Concomitant medications included prednisolone 1 mg/d and sulindac 200 mg/d, which had been given for 9 years. Methotrexate was discontinued, and folic acid 5 mg/d was started. Upon hospital admission 2 months after the regular checkup, the patient was anemic, with normal temperature. Laboratory findings were hemoglobin 7.7 g/dL, hematocrit 20.9%, leukocytes 2.0 × 103/mm3, neutrophils 0.89 × 103/mm3, and platelets 23 × 103/mm3. Bone marrow biopsy (Figure 1) revealed severe hypoplasia without the presence of malignant cells, and a chromosome test with bone marrow cells revealed abnormalities (46XX, t [10;18] [q11;q21]). From these findings, the patient was diagnosed as having MDS. She received red blood cell and platelet transfusions, empiric antibiotic therapy, prednisolone 60 mg/d, granulocyte colony-stimulating factor (75 μg/w), danazol 200 mg/d, and folic acid supplementation 5 mg/d. Two months after admission, the patient was discharged. Laboratory results at that time were: hemoglobin 9.0 g/dL, hematocrit 26.9%, leukocytes 4.0 × 103/mm3, and platelets 25 × 103/mm3. One year later, the laboratory findings were almost normal: hemoglobin 12.04 g/dL, hematocrit 39.8%, leukocytes 5.0 × 103/mm3, and platelets 127 × 103/mm3. During that time, the dosage of prednisolone had been tapered from 60 to 10 mg/d. Discussion. The Naranjo probability scale indicated a possible relationship between methotrexate therapy and pancytopenia in our patient.2 The role of the other drugs in the development of this complication could be ruled out since they were continued during the pancytopenic period and are still given without further adverse reactions. Methotrexate therapy is widely used as a potent disease-modifying treatment in patients with RA. Various rheumatic diseases have been reported to be associated with MDS.3 However, as of November 15, 2003, there have been no reports showing an association of low-dose oral methotrexate therapy and RA with the development of MDS. MDS constitutes a heterogeneous group of refractory anemias resulting from a clonal stem-cell disorder often associated with chromosomal abnormalities (deletions, inversions, translocations, trisomies, monosomies).4 Methotrexate mainly inhibits dihydrofolate reductase, has antiproliferative effects, and has only minor transforming ability even if given at high doses. Therefore, to understand the exact mechanism by which methotrexate induces chromosomal abnormalities resulting in the development of MDS, more cases similar to ours must be studied chromogenetically and accumulated. Additional studies are needed to see which actually came first in these cases: the chromosomal abnormalities or the methotrexate. Clinicians should be aware of such a risk for the development of MDS with this low-dose methotrexate therapy.

Serum transaminase elevations during pegylated interferon treatment of chronic HCV hepatitis probably induced by polyethylene glycol.

Objective: We report elevated serum alanine aminotransferase (ALT) levels during pegylated interferon (PEG-IFN)-α-2a in a patient with chronic HCV without other clinical manifestations. Case Summary: A 38-year-old man presented for HCV infection evaluation. Serum aspartate aminotransferase (AST) and ALT levels were 43 and 116 U/l, respectively; RT-PCR blood analysis revealed HCV-RNA infection. PEG-IFN-α-2b plus ribavirin treatment induced both a rapid virologic response and a normalization of transaminase plasma levels. During follow-up, an increase in transaminase and HCV-RNA values prompted us to start a new antiviral treatment with PEG-IFN-α-2a plus ribavirin. Four months later, after the follow-up, a new blood test documented both a HCV-RNA titer <50 U/ml and an increase in ALT and AST plasma levels. Immunostaining of the liver biopsy showed an accumulation of PEG-IFN-α-2a. PEG-IFN-α-2a elimination and the addition of recombinant IFN-α-2a induced normalization of the plasma transaminase levels in about 2 months. Conclusion: We postulate PEG-IFN-α-2a treatment because both the molecular weight and the distribution volume of the PEG-IFN may accumulate in the liver resulting in an increase of plasma transaminase levels. In contrast, during PEG-IFN-α-2b treatment, we did not document any increase in plasma transaminase values probably because of the lower molecular weight of the PEG.

Bilateral skin ulceration after injection of pegylated interferon-α-2b in a patient with chronic hepatitis C

1 Chair of Infective Diseases, Department of Experimental and Clinical Medicine, University‘Magna Graecia’ of Catanzaro, Regional Pharmacovigilance Center, ‘Mater Domini’ UniversityHospital, Catanzaro, Italy2 Chair of Pharmacology, Department of Experimental and Clinical Medicine, University‘Magna Graecia’ of Catanzaro, Regional Pharmacovigilance Center, ‘Mater Domini’ UniversityHospital, Catanzaro, Italy

Natural history and clinical response: "it's the virus, stupid, or is it the host?".

SummaryA major goal of modern medicine is the application of personalized therapies, consisting of decisions and practices tailored to the individual patient. Information about genetic variants, either mutant or polymorphic, represents the basis for the development of this clinical approach. Recently, several independent genome-wide association studies (GWAS) have identified two single nucleotide polymorphisms (SNPs) on the IL28B locus associated with HCV containment, spontaneous clearance, treatment response, and disease progression. In this minireview we will concisely discuss some critical genetic concepts that may have possible implications for clinical decisions in the treatment of HCV infection.

Reactivation of chronic hepatitis B during treatment with tenofovir disoproxil fumarate: drug interactions or low adherence?

We describe a case of a 61-year-old man with chronic hepatitis B, hepatitis B e antibody (HBeAb) positive, treated with tenofovir disoproxil fumarate (TDF), who developed virological and biochemical viremic reactivation with an increase in transaminase plasma levels. The patients history revealed that he had discontinued TDF about 5 days before admission and, from December 2013, had been taking venlafaxine, paroxetine and zolpidem for some episodes of depression. Clinical evaluation and laboratory findings excluded the presence of systemic diseases that might have been able to explain the drug inefficacy, while pharmacological evaluation suggested a possible drug-drug interaction. In order to assess the possible occurrence of resistance, mutational analysis of hepatitis B virus (HBV) was performed and excluded the presence of resistance for TDF. TDF was prescribed, and venlafaxine, paroxetine and zolpidem were discontinued. The follow-up at 3, 6 and 12 months documented a good response to TDF with a time-related decrease of HBV-DNA and alanine aminotransferase.

Drug-Drug Interactions: Antiretroviral Drugs and Recreational Drugs

With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.