Alan J. Wright

Treatment of Streptomycin-Susceptible and Streptomycin-Resistant Enterococcal Endocarditis

Fifty-six patients with enterococcal endocarditis received 4 weeks of antimicrobial therapy with penicillin G and streptomycin (36 patients) or, if infections were streptomycin resistant, penicillin and gentamicin (20 patients). Compared with patients who had symptoms for less than 3 months, patients with symptoms for more than 3 months had a higher relapse rate (0% versus 44%; p less than 0.001) and mortality (2.5% versus 25%; p less than 0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25%) than patients with aortic valve infections (0%) (p less than 0.01). Gentamicin-associated nephrotoxicity was more frequent (p less than 0.001) among patients treated with greater than 3 mg/kg d of gentamicin than among those treated with 3 mg or less (100% versus 20%). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for more than 3 months or patients with mitral valve infection should receive at least 6 weeks of antimicrobial therapy, but patients without these high-risk factors can be treated for 4 weeks.

Death from Inappropriate Therapy for Lyme Disease

A 30-year-old woman died as a result of a large Candida parapsilosis septic thrombus located on the tip of a Groshong catheter. The catheter had been in place for 28 months for administration of a 27 month course of intravenous cefotaxime for an unsubstantiated diagnosis of chronic Lyme disease.

Clinical Manifestations and Management of Left Ventricular Assist Device–Associated Infections

BACKGROUND Infection is a serious complication of left ventricular assist device (LVAD) therapy. Published data regarding LVAD-associated infections (LVADIs) are limited by single-center experiences and use of nonstandardized definitions. METHODS We retrospectively reviewed 247 patients who underwent continuous-flow LVAD implantation from January 2005 to December 2011 at Mayo Clinic campuses in Minnesota, Arizona, and Florida. LVADIs were defined using the International Society for Heart and Lung Transplantation criteria. RESULTS We identified 101 episodes of LVADI in 78 patients (32%) from this cohort. Mean age (± standard deviation [SD]) was 57±15 years. The majority (94%) underwent Heartmate II implantation, with 62% LVADs placed as destination therapy. The most common type of LVADIs were driveline infections (47%), followed by bloodstream infections (24% VAD related, and 22% non-VAD related). The most common causative pathogens included gram-positive cocci (45%), predominantly staphylococci, and nosocomial gram-negative bacilli (27%). Almost half (42%) of the patients were managed by chronic suppressive antimicrobial therapy. While 14% of the patients had intraoperative debridement, only 3 underwent complete LVAD removal. The average duration (±SD) of LVAD support was 1.5±1.0 years. At year 2 of follow-up, the cumulative incidence of all-cause mortality was estimated to be 43%. CONCLUSION Clinical manifestations of LVADI vary on the basis of the type of infection and the causative pathogen. Mortality remained high despite combined medical and surgical intervention and chronic suppressive antimicrobial therapy. Based on clinical experiences, a management algorithm for LVADI is proposed to assist in the decision-making process.

Meningoencephalitis Due to Blastomyces dermatitidis: Case Report and Literature Review

Infection of the central nervous system by Blastomyces dermatitidis is a rare cause of meningoencephalitis. The existence of exclusive clinical infection of the meninges in the absence of pulmonary or other foci of infection has been debated. We describe a 20-year-old man presenting with meningoencephalitis caused by B dermatitidis. Blastomycotic infection was confirmed by isolation of the organism from brain tissue obtained at biopsy. Magnetic resonance imaging demonstrated progressive enhancement of basal meninges with involvement of bilateral basal ganglia and thalami. Treatment with amphotericin B arrested further neurologic decline. However, clinical and radiographic follow-up suggested damage to diencephalic structures. The diagnosis of blastomycotic meningoencephalitis is difficult to establish because no sensitive serologic test exists, and attempts to isolate the organism in cerebrospinal fluid obtained by lumbar puncture generally fail. A biopsy specimen of brain tissue is frequently necessary for the diagnosis. Survival is possible with timely initiation of therapy.

Cidofovir Treatment of Progressive Multifocal Leukoencephalopathy in a Patient Receiving Highly Active Antiretroviral Therapy

Progressive multifocal leukoencephalopathy (PML), a frequently fatal demyelinating disease caused by JC virus, occurs as an opportunistic infection in patients with acquired immunodeficiency syndrome. Curative therapy has been elusive, but recent reports suggest its improvement after institution of highly active antiretroviral therapy (HAART). We describe a case of PML that developed 6 months after the patient, a 55-year-old man, began to receive HAART. The PML progressed despite good virologic and immunologic response to HAART. Substantial symptomatic and radiographic improvement occurred after the addition of cidofovir to the treatment regimen. We reviewed the scientific literature on this rare occurrence of PML after institution of HAART and describe the patient characteristics, potential pathogenesis, and therapeutic options, including the successful use of cidofovir as an adjunctive agent.

Prosthetic valve endocarditis: clinicopathological correlates in 122 surgical specimens from 116 patients (1985-2004)

BACKGROUND Few studies have documented the clinicopathological features of prosthetic valve endocarditis independently of native valve endocarditis. STUDY DESIGN Retrospective analysis of patients undergoing cardiac surgery for prosthetic valve endocarditis at our institution (1985-2004). METHODS Medical records and microscopic slides were reviewed from 116 patients for demographics, infecting organisms, comorbidities, and pathologic features. RESULTS Patients were 12-86 years old (mean, 59 years). Among 122 valves, 64% were from men and 67% were purely regurgitant. Aortic prosthetic valve endocarditis frequently affected men (76%); mitral prosthetic valve endocarditis often affected women (62%). Embolization occurred in 35% and heart failure in 32%. Prevalent predisposing conditions were the prosthetic valve alone (43%) and diabetes mellitus (20%). Prosthetic valve endocarditis was aortic or mitral in 98% and was active in 70%. Annular abscess or paravalvular leak affected mechanical valves more frequently than bioprosthetic (89% vs. 65%; P=.001). Causative organisms (n=116) included Staphylococcus aureus (30%), coagulase-negative staphylococcus (22%), viridans streptococci (18%), enterococci (10%), other streptococci (8%), and other organisms (12%). S. aureus was the most prevalent cause of early-onset (38%) and late-onset (30%) prosthetic valve endocarditis. Coagulase-negative staphylococcus caused early-onset (31%) and most intermediate-onset (40%) disease and had a shorter median implantation-to-infection time than other organisms (6.5 vs. 61.3 months; P<.001). Viridans streptococci and enterococci primarily caused late-onset endocarditis. For active infections by cocci, most cases exhibited strong Gram staining, but four showed only strong Grocott methenamine silver staining. CONCLUSIONS Cocci accounted for 83% of infections. Early-onset prosthetic valve endocarditis was primarily staphylococcal, and late-onset prosthetic valve endocarditis resembled native valve endocarditis. Both Gram and Grocott methenamine silver stains were necessary to reliably identify organisms microscopically.

OPA1 in multiple mitochondrial DNA deletion disorders

Disorders of mitochondrial DNA (mtDNA) maintenance are a major cause of sporadic and inherited neurologic disease,1 but the underlying nuclear gene defects have yet to be identified in many patients. Following the recent description of multiple mtDNA deletions in seven families with mutations in OPA1 ,2–4 we determined the frequency of OPA1 mutations in adult patients with multiple mtDNA deletions who did not have mutations in POLG1, POLG2, SLC25A4, and PEO1 . ### Methods. OPA1 and exon-intron boundaries was sequenced in 21 probands with a mosaic defect of cytochrome c oxidase (COX) and multiple deletions of mtDNA in skeletal muscle (table; e-methods on the Neurology ® Web site at www.neurology.org). View this table: Table Clinical, histochemical, and genetic findings in 21 probands ### Results. Eighteen patients had synonymous substitutions in OPA1 , or single nucleotide polymorphisms (SNPs) present in >1% of the control population (tables e-1 and e-2). c.575C>T was detected in 3.5% of 144 matched population controls (95% CI = 1.8–6.4). Pathogenic variants were detected in three subjects (14.2% of the 21): c.1334G>A/p.R445H in patients 16 and 20 …

Hereditary Sensory Neuropathy With Sensorineural Deafness and Early-Onset Dementia

Article abstract-We report a kindred with autosomal dominantly inherited sensory neuropathy associated with sensorineural hearing loss and early-onset dementia. This kindred provides further evidence of the clinical variability among kindreds with hereditary sensory neuropathy, suggesting genetic heterogeneity. NEUROLOGY 1995;45: 560-562

Cure of a solitary abscess with antibiotic therapy Case report

A solitary brainstem abscess is uncommon. The use of antibiotics and surgical aspiration or excision of a brainstem abscess has resulted in survivors. Survival after treatment of a brainstem abscess with antibiotics alone has been reported rarely, and we present the eighth study case. The patient made an excellent recovery after 12 weeks of antibiotics, with 8 weeks completed as an outpatient. Medical management of a solitary brainstem abscess in an immunocompetent patient is feasible and may result in a complete cure with antibiotics only. Completion of IV antibiotics as an outpatient is viable and cost-effective in selected patients.

A cluster of Mycobacterium wolinskyi surgical site infections at an academic medical center.

OBJECTIVE To study a cluster of Mycobacterium wolinskyi surgical site infections (SSIs). DESIGN Observational and case-control study. SETTING Academic hospital. PATIENTS Subjects who developed SSIs with M. wolinskyi following cardiothoracic surgery. METHODS Electronic surveillance was performed for case finding as well as electronic medical record review of infected cases. Surgical procedures were observed. Medical chart review was conducted to identify risk factors. A case-control study was performed to identify risk factors for infection; Fisher exact or Kruskal-Wallis tests were used for comparisons of proportions and medians, respectively. Patient isolates were studied using pulsed-field gel electrophoresis (PFGE). Environmental microbiologic sampling was performed in operating rooms, including high-volume water sampling. RESULTS Six definite cases of M. wolinskyi SSI following cardiothoracic surgery were identified during the outbreak period (October 1, 2008-September 30, 2011). Having cardiac surgery in operating room A was significantly associated with infection (odds ratio, 40; P = .0027). Observational investigation revealed a cold-air blaster exclusive to operating room A as well a microbially contaminated, self-contained water source used in heart-lung machines. The isolates were indistinguishable or closely related by PFGE. No environmental samples were positive for M. wolinskyi. CONCLUSIONS No single point source was established, but 2 potential sources, including a cold-air blaster and a microbially contaminated, self-contained water system used in heart-lung machines for cardiothoracic operations, were identified. Both of these potential sources were removed, and subsequent active surveillance did not reveal any further cases of M. wolinskyi SSI.