Linezolid-associated toxic optic neuropathy.

The oxazolidinone antimicrobial linezolid is effective against gram-positive bacteria. Although maximal recommended therapy is 28 days, treatment durations greater than this are common. Linezolid may cause reversible optic neuropathy and irreversible peripheral neuropathy after months of treatment. Three cases of linezolid-induced optic and peripheral neuropathy are described, and previously reported cases of linezolid-induced optic neuropathy are reviewed. The mechanism of neural toxicity may be impairment of mitochondrial protein synthesis.

West Nile virus infection: a new acute paralytic illness.

OBJECTIVE: To determine the clinical, laboratory, electrodiagnostic, radiologic, and pathologic characteristics that define the spectrum of CNS disease caused by West Nile virus (WNV) infection. METHODS: The records of all patients hospitalized at the Cleveland Clinic from August 2002 to September 2002 with WNV infection were reviewed. RESULTS: Of 23 cases, the median age was 74 years old, and 74% were men. Symptoms included fever (100%), altered mental status (74%), gastrointestinal complaints (43%), back pain (35%), and rash (26%). In half, meningitis or encephalitis overlapped with flaccid weakness that progressed over 3 to 8 days, with a tendency to be proximal and asymmetric. Laboratory abnormalities included hyponatremia (30%) and initial CSF neutrophilic pleocytosis. Electrodiagnostic studies in two patients showed reduced motor amplitudes with normal conduction velocities and active denervation. In two other patients, reduced sensory amplitudes were also seen. MRI changes included cauda equina enhancement and parenchymal spinal cord signal abnormalities and parenchymal or leptomeningeal signal changes in the brain. Autopsy in three cases showed chronic perivascular inflammation in the brain and inflammatory changes with anterior horn cell loss in the spinal cord. CONCLUSION: An overlapping spectrum of meningitis, encephalitis, and myeloradiculitis occurs in CNS WNV infection. Fever, rash, abdominal and back pain, preceding a proximal, asymmetric flaccid weakness, with CSF pleocytosis help distinguish the motor syndrome from Guillain-Barré syndrome. Pathologic changes in the CNS resembled poliomyelitis.

Clinical characteristics of 13 solid organ transplant recipients with ganciclovir-resistant cytomegalovirus infection.

BACKGROUND: Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients. OBJECTIVE: To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center. METHODS: Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data. RESULTS: Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis. CONCLUSIONS: GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.

Protease-sparing regimen in a real-life practice with naïve patients: an equal opportunity approach?

PURPOSE: Proven clinical efficacy of protease-sparing regimens (PSR) has been shown. Concerns exist about broad applicability of these regimens in advanced naïve patients. Recent reports have associated a rise in liver enzymes with nevi rapine; however, no data exist with efavirenz. METHOD: 17 consecutive antiretroviral-naïve HIV patients were started on a PSR with efavirenz plus two nucleoside reverse transcriptase inhibitors. Baseline liver enzymes, serum CD38, CD4, and HIV viral load data were collected. Correlation between change in viral load and immune reconstitution on therapy were compared to baseline laboratory values. RESULTS: All patients had a mean viral load decrease of >2 logs, including patients with low initial CD4% or high viral load, and there was no increase of liver enzymes observed at a median follow-up of 42 weeks (range 17-78). There was a perfect correlation between the change in viral load and the initial viral load (p <.0001, r = 1.00) including patients with viral load > or =100,000 copies/mL and CD4 count< or =50 (n = 5). Even patients with low initial CD4 had a significant percentage increase in CD4 count (p <.0002, r = 0.7880). CD38% showed a positive correlation with change in viral load (p =.046, r = 0.522). CONCLUSION: All patients experienced a mean viral load decrease of >2 logs (88% less than 400 copies/mL and 35% less than 20 copies/mL). There were no observed increases in liver enzymes. Patients with low CD4 counts, high initial viral load, or high CD38 expression still experienced a significant change in viral load.

New developments in long-term treatment of HIV: the honeymoon is over.

New recommendations advise starting highly active antiretroviral therapy (HAART) slightly later in the course of HIV disease compared with earlier guidelines. HAART has prolonged life in HIV patients, altering the spectrum of problems being treated. As the immune system recovers, long-term prophylaxis against some secondary infections can be discontinued. The problem, however, is that HAART also has serious long-term side effects such as lactic acidosis, lipodystrophy, and the promotion of drug-resistant strains of HIV.

Update on antiviral therapy for genital herpes infection.

For the primary infection of genital herpes, antiviral therapy with acyclovir is the gold standard. For recurrences, there are two options: antiviral treatment of each outbreak as it arises, or suppression of outbreaks with daily oral therapy. Patients tend to prefer the latter because it can decrease the number and severity of outbreaks, but it increases asymptomatic viral shedding and, therefore, the risk of unwittingly transmitting herpes simplex virus to uninfected sexual partners.

Use of an HBV-DNA hybridization assay in the evaluation of equivocal hepatitis B virus tests in solid organ donors.

CONTEXT: Serological markers for the hepatitis B virus are routinely used in the evaluation of potential organ donors. However, serological tests can be associated with significant false or equivocal results and may not be indicative of the true risk of hepatitis B infection. Studies have recently questioned the significance of an isolated hepatitis B core antibody test in evaluating the suitability of solid organs for transplantation. The ability to detect hepatitis B virus DNA may prove useful when the diagnosis of hepatitis B infection is in doubt. DESIGN: Serum samples from 16 donors with equivocal or positive hepatitis B core antibody and/or hepatitis B surface antigen serological screening tests were retrospectively tested for the presence of hepatitis B DNA. Any available follow-up data on the placement of organs from these donors was obtained. RESULTS: One of the 16 (6.3%) donors tested positive for the presence of hepatitis B DNA, but organs from this donor were not recovered or transplanted. Follow-up on 14 organs recovered and transplanted from 6 donors in this group did not show clinical and/or laboratory evidence of hepatitis B infection in the recipients. CONCLUSIONS: In our donor population, there was a low incidence (6.3%) of donors with equivocal or positive hepatitis B core antibody and/or hepatitis B surface antigen serological screening tests who subsequently demonstrated the presence of detectable hepatitis B DNA. Posttransplantation follow-up of the recipients of 14 recovered organs failed to demonstrate any cases of posttransplant hepatitis B infection.

Candida glabrata Fungemia. Clinical features of 139 patients.

Candida species are now the fourth leading cause of nosocomial bloodstream infection in hospitalized patients, and non-Candida albicans species now surpass Candida albicans. The clinical features of the most common non-Candida albicans species, Candida (Torulopsis) glabrata, have not been well studied. We retrospectively reviewed the clinical features of 139 patients with C. glabrata blood-stream infection over a period of 7 years. The mean age of patients was 62 years, and the most common admitting diagnoses were malignancy (28%) and coronary artery disease (18%). The most common identified portals of entry were abdominal (22%) and intravascular catheters (16%). At the time of fungemia, 63% of patients had fever, 45% had change in mental status, and 30% were in septic shock. Three of 50 patients examined by an ophthalmologist had chorioretinitis. The overall hospital mortality was 49%. Factors associated with increased mortality in a regression model were prior abdominal surgery (odds ratio [OR] = 2.8; 95% confidence interval [CI] = 1.2-6.3, p = 0.01), and an elevated creatinine (OR = 2.2; 95% CI = 1.0-4.7, p = 0.05). When early deaths (< or = 72 hours) were censored, amphotericin B treatment and total dose were associated with reduced mortality (OR = 0.2; 95% CI = 0.1-0.4, p < 0.001). Nosocomial C. glabrata fungemia is not just a disease of debilitated and neutropenic patients, but affects a wide variety of patients and is associated with a high mortality.

AIDS update 1999: viral reservoirs and immune-based therapies.

The advent of highly active antiretroviral therapy (HAART) has brought about a dramatic decline in opportunistic infections, hospitalizations, and mortality in AIDS patients. However, the recent discovery that HIV can lay dormant in quiescent T cells and other tissues even in the face of HAART therapy has dampened optimism for a cure for AIDS, though it suggests new avenues of research.

Microsporidia infection in transplant patients.

BACKGROUND: Microsporidia are the most common cause of chronic diarrhea in patients infected with human immunodeficiency virus. Patients who have undergone organ transplantation may also be infected. The precise immune defect and the clinical picture in transplant patients have not been studied. METHODS: We report a case of microsporidia infection in a heart transplant patient and review three other cases reported in the literature. RESULTS: Infection in three solid organ transplant patients occurred when the patients were receiving immunosuppressive therapy for rejection 1.5-3 years after transplantation. Patients had chronic diarrhea, vomiting, dyspepsia, and weight loss for 1 month to 3 years. CONCLUSIONS: Microsporidia may be the cause of chronic unexplained diarrhea and gastrointestinal disturbances in transplant patients. Defects in cell-mediated immunity probably play a role in maintaining the chronicity of this infection. Specific screening requests should be made to the microbiology laboratory when microsporidia infection is suspected.

Sternotomy infection with Mycoplasma hominis: a cause of "culture negative" wound infection.

Wound infections with Mycoplasma species are unusual; diagnosis may be delayed because of the growth characteristics of this organism. We report Mycoplasma hominis infection of sternotomy wounds in two patients. The first presented with fever and drainage from the incision 1 week after coronary artery bypass grafting. The other patient presented with drainage from the incision three weeks after double-lung transplantation. In both cases, initial cultures were negative, but the typical colonial morphology of M. hominis was subsequently detected. Successful treatment consisted of debridement and long courses of antibiotic therapy; omental flap grafting was eventually required for the second patient. Other published cases were reviewed and compared with the newly reported cases.

Pro: antibiotics for chronic bronchitis with exacerbations.

Over the years, there has emerged a considerable body of evidence supporting the importance of antimicrobial therapy in exacerbations of chronic bronchitis. The following lines of evidence suggest that most acute exacerbations are caused by bacterial infection: (1) the individual with chronic bronchitis is susceptible to bacterial infection as a consequence of local damage from prolonged cigarette smoking; (2) subtle defects in the local immune system can be shown, including impaired particle transport, defective immunoglobulin A production, chronic mucous impaction, and defective neutrophil phagocytosis; (3) acute bronchitic exacerbations are associated with a proliferation of pathogenic bacteria in the lower respiratory tract, based on quantitative culture data obtained by bronchoscopy with a protected specimen brush; (4) viral respiratory infections, which were once linked to over 50% of purulent exacerbations, probably account for only a minority of bronchitic exacerbations; (5) some "culture negative" exacerbations may be caused by bacteria susceptible to antibiotics such as Mycoplasma pneumoniae or Chlamydia pneumoniae. There are also secondary effects of bacteria that are potentially amenable to antibiotic therapy. Bacteria that colonize the respiratory tract of chronic bronchitics cause direct damage to the respiratory epithelium. Lipooligosaccharide, a major component of the outer membrane of Haemophilus influenzae, is an endotoxin-like mediator of respiratory cell damage. The host inflammatory response to bacterial proliferation is ineffective and may be potentially harmful; the enzyme neutrophil elastase is released by the host during phagocytosis of bacteria and may lead to progressive airway damage. In addition, bacterial superinfections may complicate viral exacerbations of chronic bronchitis. Clinical trials examining the efficacy of antibiotic therapy in mild to moderate exacerbations of chronic bronchitis have yielded conflicting results, caused in part to fundamental differences in study design. The major double-blinded and placebo-controlled studies suggest a trend in favor of antimicrobial therapy, although the effect is modest. For the individual patient, the risks of antimicrobial therapy are small compared with the potential benefits of returning to work earlier and avoiding the rare case of respiratory decompensation.

Aberrant Histoplasma capsulatum. Confirmation of identity by a chemiluminescence-labeled DNA probe.

A cottony, light tan, filamentous fungus with pear-shaped microconidia and lacking tuberculated macroconidia was isolated from a bronchial lavage specimen. Subculture on several media at 37 degrees C failed to convert the fungus to a yeast form after several weeks; attempts at in vivo conversion in mice were also unsuccessful. Sera obtained several months apart showed M bands with Histoplasma capsulatum (HC) antigen by immunodiffusion and an increase in complement fixation titers with mycelial and yeast phase antigens of HC. Parallel identity was obtained on two occasions with exoantigen culture confirmation reagents for HC from Immuno-Mycologics as well as one of identity with Nolan reagents. Extracts from four Chrysosporium spp. strains had no identity reactions with HC with either kit. The fungus was identified as HC by the Accuprobe Histoplasma chemiluminescence-labeled DNA probe directed at ribosomal RNA, whereas all four Chrysosporium spp. isolates tested negative. DNA probes are a fast and accurate method to confirm the identity of aberrant fungal isolates.