Massimo Fantoni

Drugs and Cardiotoxicity in HIV and AIDS

Abstract: The advent of potent antiretroviral drugs in recent years has had an impressive impact on mortality and disease progression in HIV‐infected patients, so that issues related to long‐term effects of drugs are of growing importance. Hyperlipidemia, hyperglycemia, and lipodystrophy are increasingly described adverse effects of highly active antiretroviral therapy (HAART), in particular when protease inhibitors are used. Hyperlipidemia is strikingly associated with the use of most available protease inhibitors, with an estimated prevalence of up to 50%. Because of the short observation period and the small number of cardiovascular events, epidemiological evidence for an increased risk of coronary heart disease in HIV‐infected patients treated with HAART is not adequate at present; however, it is likely that shortly more data will accumulate to quantify this risk. Before starting HAART and during treatment it is reasonable to evaluate all patients for traditional coronary risk factors, including lipid profile. Among the drugs that are currently used in HIV+ patients, antibacterials, antifungals, psychotropic drugs and anti‐histamines have been associated with QT prolongation or torsade de pointe, a life‐threatening ventricular arrhythmia. Among the risk factors that may precipitate an asymptomatic electrocardiographic abnormality into a dangerous arrhythmia is the concomitant use of drugs that share the CYP3A metabolic pathway. Since most protease inhibitors are potent inhibitors of CYP3A, clinicians should be aware of this potentially dangerous effect of HAART. Anthracyclines are potent cytotoxic antibiotics that have been widely used for the treatment of HIV‐related neoplasms. Their cardiotoxicity is well known, ranging from benign and reversible arrhythmias to progressive severe cardiomyopathy. The increased survival and quality of life of HIV+ patients emphasize the importance of a high awareness of adverse drug‐related cardiac effects.

Rapid HIV-RNA decline following addition of raltegravir and tenofovir to ongoing highly active antiretroviral therapy in a woman presenting with high-level HIV viraemia at week 38 of pregnancy

patients are seen by a doctor at least once every week. All doses ,800 mg are diluted to 20 mL with normal saline. Larger doses are given as the neat 40 mg/mL solution supplied in the manufacturers’ vials. In the period between November 1995 and October 2009, we documented the administration of 5593 doses (3652 of tobramycin and 1941 of gentamicin). The drugs were administered in 361 courses (244 of tobramycin and 117 of gentamicin) to 132 patients. Sixty-seven of these patients had cystic fibrosis and received multiple courses. Twelve of the remaining 65 had bronchiectasis and also received more than one course. The other remaining patients were treated for a variety of diagnoses, typically requiring only one course. One hundred and forty-five courses were administered to children and 216 to adults. The ages of the patients ranged from 3 to 84 years. The median dose was 360 mg of tobramycin and 320 mg of gentamicin in cystic fibrosis, and 240 mg of tobramycin and 170 mg of gentamicin in those without cystic fibrosis. The median course duration was between 15 and 18 days across the same groups. One patient, a middle-aged female with complex medical problems, developed vestibular toxicity and some hearing loss 16 h after her last dose of 320 mg of tobramycin. There has never been the suggestion of neuromuscular toxicity or hearing loss at the time of injection. Current recommendations are that tobramycin and gentamicin be given by infusion over ≥30 min. We have shown that tobramycin and gentamicin can be safely administered by slow push over 3–5 min. We recommend that consideration be given to the use of this simple method as the standard of care.

Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients

BackgroundEfavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption.MethodsPatients starting any cART regimen including EFVu2009+u20092NRTIs or switching to EFVu2009+u20092NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model.ResultsOverall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, pu2009<u20090.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, pu2009=u20090.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, pu2009=u20090.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk.ConclusionsIn our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.

Letter: faecal microbiota transplantation in combination with fidaxomicin to treat severe complicated recurrent Clostridium difficile infection

SIRS, We read with great interest the use of faecal microbiota transplantation (FMT) and antibiotics in patients with severe and severe/complicated Clostridium difficile infection (CDI) described by Fischer et al. In this regard, we would like to give our contribution to the management of these cases. We have recently treated a patient suffering from amyotrophic lateral sclerosis (ALS) with CDI refractory to standard therapy (vancomycin plus metronidazole) and therefore at high risk for colectomy. We offered the patient a compassionate use protocol consisting of sequential faecal infusions via colonoscopy in combination with fidaxomicin instead of vancomycin. Indeed, fidaxomicin is a narrow-spectrum oral macrocyclic antibiotic for the treatment of CDI with a bactericidal effect (acts by inhibition of RNA synthesis) and it has been reported that it causes less disruption of the gut microbiota and lower rates of recurrence compared to vancomycin, while the safety profile is comparable to oral vancomycin. Based on our experience and considering the patient’s clinical condition and the evidence of pseudomembranes at the first colonoscopy, we decided to perform three faecal infusions and to continue fidaxomicin until the last procedure. Patient clinical improvement was assessed daily, with a reduction in stool number and with progressive resolution of pseudomembranes, even though, at the time of last infusion, there were still signs of colonic inflammation (mucosal hyperaemia and oedema). Therefore, we agree with Fischer and colleagues about the use of combined treatment for severe/complicated CDI patients, but with the description of our case we propose a new possible combined strategy based on FTM plus fidaxomicin for the management of this patient group. However, further larger studies are warranted to support our findings.

Tubercular Osteomyelitis of the Second Metatarsal: A Case Report

A number of studies have described the osteoarticular involvement of tuberculosis, but very few cases of tubercular osteomyelitis of the foot have been reported. We describe a case of spina ventosa affecting the second metatarsal, with a review of the literature and description of the clinical manifestations, diagnostic images, and treatment of skeletal tuberculosis.

Non-Hodgkin's lymphoma of the maxillary sinus in a patient with acquired immunodeficiency syndrome

Non-Hodgkins lymphoma (NHL) is one of the most common malignancies in patients infected with human immunodeficiency virus (HIV): it occurs 25-60 times more frequently in HIV-infected patients than in the general population. This neoplasm in acquired immunodeficiency syndrome (AIDS) patients is a highly aggressive tumour with a poor prognosis and tends to develop in extranodal sites, such as the central nervous system, digestive tract and bone marrow. NHL involving the paranasal sinuses is rare in HIV-infected patients, and is likely to be confused clinically and radiographically with sinusitis; moreover, its optimal treatment is currently uncertain. We present a case of NHL involving the left maxillary sinus in a patient with AIDS. The patient was treated with systemic chemotherapy (low dose-CHOP), but the malignancy did not respond. Subsequently, he was treated with local maxillary sinus irradiation which resulted in partial regression of the neoplasm and in decrease of local symptoms.

Candida utilis catheter-related bloodstream infection

Central venous catheter-related fungemia are increasing in the last years, also due to rare fungi. We report the case of a Candida utilis catheter-related bloodstream infection in a patient with metastatic carcinoma of the bladder and a long term totally implanted venous catheter. The diagnosis was done by paired blood cultures and differential time to positivity. The Candida species was rapidly identified by MALDI-TOF mass spectrometry. The patient was successfully treated with anidulafungine.

Impact of antibiotic stewardship on perioperative antimicrobial prophylaxis

OBJECTIVEnAntibiotic prophylaxis (AP) is useful to prevent antimicrobial overuse, misuse and abuse,xa0as well against the occurrence of surgical site infections (SSIs). This study aimed to describe the implementation of a quality improvement intervention on AP for elective surgery, as informal interviews showed axa0lower than expected compliance with internal recommendations, and to evaluate interventions effect in terms of main drug consumption.nnnDESIGNnA quality improvement intervention on all elective cases within 14 main surgical departments was performed. SQUIRE 2.0 guidelines were used in designing and reporting.nnnSETTINGnThe intervention was implemented in an Italian Teaching Hospital 2 years after the adoption of internal evidence-based AP recommendations.nnnPARTICIPANTSnProfessionals involved in elective surgery.nnnINTERVENTIONSnThe intervention was structured into two phases: a survey was conducted during two non-consecutivexa0weeks period (April-May 2013) to assess the adherence to the international guidelines in AP; surveys results were presented and discussed with all the surgical teams (December 2013-April 2014).nnnMAIN OUTCOME MEASURESnImpact on cefazolin consumption (in defined daily doses per 100 procedures).nnnRESULTSnData of AP for 653 surgical procedures in terms of type, timing, duration, excess and defect were analyzed. An optimal AP rate resulted in 48.1% cases. Reduction in cefazolin usexa0(-21.5%) and cost (-22.9%) was registered.nnnCONCLUSIONSnThough results cannot be generalized to all hospital populations, the implemented intervention is likely to improve AP consequently improving quality of care and reducing costs. Further studies are needed to evaluate specific outcomes such as rate of SSIs and antibiotic resistance.

Do genetic polymorphisms associated with inflammation/lipodystrophy or endothelial damage predict carotid alterations in HIV+ subjects under cART?

Methods The following variables were collected from 59 HIV+ subjects attending our outpatient department between Jan. 2007 and June 2008: traditional CV risk factors; time and type of exposure to cART; genetic polymorphisms associated with inflammation and lipodystrophy (ApoE, LPL, MDR1 3435, TNF238 and 308, adiponectin 45 and 276); endothelial adhesion molecules and platelet activation markers (ICAM-1, t-PA, PAI-1, P-selectin); M-mode carotid duplex ultrasound to measure intima-media thickness (IMT, normal value <0.6 mm), distensibility index (DI, normal value > 0.41 mm), presence of plaques (IMT > 1 mm).

Tubercular osteomyelitis of the second metatarsal bone: case report

Many studies have described the osteoarticular involvement of tuberculosis, but very few cases of tubercular osteomyelitis of the foot have been reported. We describe a case of spina ventosa affecting the second metatarsal bone, and review the literature to describe the clinical manifestation, imaging aspects and the treatment of skeletal tuberculosis.