Immune reconstitution inflammatory syndrome involving the central nervous system in a patient with HIV infection: a case report and review of literature.

IRIS is described as a paradoxical deterioration of clinical status upon initiation of combined anti-retroviral therapy (cART) in patients with HIV infection. Immune reconstitution inflammatory syndrome (CNS-IRIS) involving the central nervous system is rarely reported. We describe the case of 57-year-old man who developed a fatal case of CNS- IRIS. A rapid deterioration of neurological status was associated with progression of patchy T2-weighted hyperintensities involving different vascular territories on brain MRI. Diagnosis of CNS-IRIS is based of laboratory and radiologic findings, however brain biopsy is supportive. Despite immune restoration being involved in clinical deterioration, discontinuation of cART is not recommended. The use of corticosteroids is highly controversial. Prompt recognition of CNS-IRIS is crucial for preventing neurological complications and ensuing sequelae.

Symbiotic bacteria induced necrotizing pancreatitis.

CONTEXT: Intestinal flora and anaerobes are frequently implicated in causing infectious necrotizing pancreatitis however Bifidobacterium and Veillonella have rarely been isolated as the causative agents. Bifidobacterium and Veillonella are commensal anaerobes which reside in gastrointestinal tract and help deconjugate bile acids. Bifidobacterium is also frequently used in probiotics. CASE REPORT: We present a 68-year-old man who initially presented with gallstone pancreatitis but eventually developed Bifidobacterium and Veillonella species induced necrotizing pancreatitis and pseudocyst formation. CONCLUSION: Under rare circumstances commensal gut flora can turn pathogenic which can lead to life-threatening morbidity and may even result in mortality.

Moxifloxacin induced fatal hepatotoxicity in a 72-year-old man: a case report.

Moxifloxacin is a newer-generation synthetic fluoroquinolone that is used for treatment of acute bacterial sinusitis, acute exacerbation of chronic bronchitis, community acquired pneumonia, intra-abdominal infections and skin/skin structure infections. We describe a case of fatal hepatotoxicity caused by Moxifloxacin in a 72-year-old man. He presented with jaundice and epigastric tenderness that started one week after being treated for acute exacerbation of his chronic bronchitis with Moxifloxacin by his primary care physician. He was admitted to intensive care unit for close monitoring. His labs showed marked elevation in liver enzymes and bilirubin. His condition continued to deteriorate in intensive care unit despite supportive care. Acute hepatic failure which resulted in his death was attributed to idiosyncratic reaction to Moxifloxacin.

Pharmacokinetics of linezolid in subjects with renal dysfunction.

Linezolid is a member of a new, unique class of synthetic antibacterial agents called oxazolidinones that are effective against gram-positive bacteria, including vancomycin-resistant organisms. We tested the hypothesis that the linezolid clearance would not be altered in subjects with renal dysfunction. Twenty-four subjects with renal function that ranged from normal to severe chronic impairment were enrolled, including patients with end-stage renal disease who were maintained on hemodialysis. Hemodialysis subjects were studied while they were both on and off dialysis. Linezolid was administered as a single oral 600-mg dose, and plasma and urine samples were assayed for linezolid and metabolites for 48 h for all subjects and for up to 96 h for those subjects with impaired renal function not on dialysis. The total apparent oral clearance of linezolid did not change with renal function and ranged from 92.5 to 109.6 ml/min for subjects not requiring dialysis. For subjects on dialysis, the total apparent oral clearance increased from 76.6 ml/min on their off-dialysis day to 130.0 ml/min on their on-dialysis day. Approximately one-third of the dose was removed by dialysis. However, those subjects with severe renal insufficiency (creatinine clearance, <40 ml/min) and those with end-stage renal disease maintained on hemodialysis had higher concentrations of both metabolites. We conclude that no adjustment of the linezolid dosage is needed in subjects with renal dysfunction or subjects on hemodialysis.

Pharmacokinetics and tolerance of single- and multiple-dose oral or intravenous linezolid, an oxazolidinone antibiotic, in healthy volunteers.

AIMS: To determine the pharmacokinetics and tolerance of oral and intravenous linezolid, an oxazolidinone antibiotic, in healthy volunteers following single- and multiple-dose administration. METHODS: In two randomized, double-blind, placebo-controlled, dose-escalating trials, subjects were exposed either to oral (375, 500 or 625 mg) or intravenous (500 or 625 mg) linezolid or placebo twice daily. Serial blood and urine samples were obtained after the first- and multiple-dose administrations for up to 18 days. Non-compartmental pharmacokinetic analyses were used to describe the disposition of linezolid. RESULTS: Plasma linezolid concentrations and area under the concentration-time curves increased proportionally with dose irrespective of the route of administration. Plasma linezolid concentrations remained above the MIC90 for susceptible target pathogens (4.0 mg/L) for the majority of the 12 h dosing interval. Mean clearance, half-life and volume of distribution were similar irrespective of dose for both the oral and intravenous routes. Linezolid was well tolerated and the frequency of drug-related adverse events was similar between the linezolid and placebo groups. CONCLUSIONS: Oral and intravenous linezolid exhibit linear pharmacokinetics, with concentrations remaining above the target MIC90 for most of the dosing interval. These results support a twice-daily schedule for linezolid and demonstrate the feasibility of converting from intravenous to oral dosing without a dose adjustment.

Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program.

Linezolid was provided for treatment of multidrug-resistant, gram-positive infections through a compassionate-use program. Patients (n=796) received 600 mg of linezolid intravenously or orally every 12 h (828 treatment courses). Bacteremia was present in 46% of infections, endocarditis was present in 10.6%, and line-related infections were present in 31.1%. Other infections included intraabdominal infections (15.1%), complicated skin and skin-structure infections (13.3%), and osteomyelitis (10.7%). Causative pathogens included vancomycin-resistant enterococci (66.3%) and methicillin-resistant staphylococci (22.1%). Clinical intent-to-treat (ITT) outcomes in the evaluable population were as follows: cure, 73.3%; failure, 6.8%; and indeterminate, 19.9%. Microbiological ITT outcomes in evaluable patients were as follows: cure, 82.4%; failure, 14.1%; and indeterminate, 3.5%. At the test of cure assessment, the clinical cure and microbiological success rates were 91.5% and 85.8%, respectively. The most common adverse events possibly related to linezolid use were gastrointestinal disturbances (9.8% of cases), thrombocytopenia (7.4% of cases), decreased hemoglobin/hematocrit levels (4.1% of cases), and cutaneous reactions (4.0% of cases). Linezolid provided high rates of clinical cure and microbiological success in this complicated patient population, with very good overall tolerance.

Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.

Linezolid, the first available member of a new antibiotic class, the oxazolidinones, is broadly active against gram-positive bacteria, including drug-resistant strains. In this randomized, open-label trial, hospitalized adults with known or suspected methicillin-resistant Staphylococcus aureus (MRSA) infections were treated with linezolid (600 mg twice daily; n=240) or vancomycin (1 g twice daily; n=220) for 7-28 days. S. aureus was isolated from 53% of patients; 93% of these isolates were MRSA. Skin and soft-tissue infection was the most common diagnosis, followed by pneumonia and urinary tract infection. At the test-of-cure visit (15-21 days after the end of therapy), among evaluable patients with MRSA, there was no statistical difference between the 2 treatment groups with respect to clinical cure rates (73.2% of patients in the linezolid group and 73.1% in the vancomycin group) or microbiological success rates (58.9% in the linezolid group and 63.2% in the vancomycin group). Both regimens were well tolerated, with similar rates of adverse events.