High-Dose Oral Posaconazole for the Treatment of Recalcitrant Fungal Keratitis.

PURPOSE: To report the successful treatment of 3 cases of recalcitrant fungal keratitis (FK) with high-dose oral posaconazole. METHODS: This is a series of 3 patients from a single academic center with a culture-positive FK who were treated with oral posaconazole after failing to respond to conventional treatments. RESULTS: All 3 patients had a history of contact lens wear. Two of the 3 cases were culture positive for Fusarium and the other for Paecilomyces . The infections of all 3 failed to respond to conventional antifungal therapies including varying combinations of topical, systemic, and intraocular antifungal therapies. All 3 cases rapidly responded to high-dose oral posaconazole ranging from 500 to 600 mg once daily. In 1 case, multiple courses of high-dose therapy were required to treat delayed recurrences of a latent infection. There were no significant adverse effects with the elevated dose, and treatment was administered with the guidance of an infectious disease specialist. CONCLUSIONS: In cases of recalcitrant FK failing to respond to conventional therapies, high-dose posaconazole, in the delayed-release tablet formulation, can be an effective treatment option.

Real-time polymerase chain reaction (PCR) cycle threshold and Clostridioides difficile infection outcomes.

OBJECTIVE: Clostridioides difficile infection (CDI) causes significant morbidity and mortality; however, the diagnosis of CDI remains controversial. The primary aim of our study was to evaluate the association of polymerase chain reaction (PCR) cycle threshold (Ct) values with CDI disease severity, recurrence, and mortality among adult patients with CDI. DESIGN: Retrospective cohort study. SETTING: Single tertiary-care hospital. PATIENTS: Adult patients diagnosed with hospital-onset, healthcare facility-associated CDI from June 2014 to September 2015. METHODS: We performed a retrospective chart review of included patients. Univariate and multivariable logistic regression methods were used to evaluate the association between Ct values and CDI severity, 8-week recurrence, and 30-day mortality. RESULTS: Among 318 included patients, 51% were male and the mean age was 62 years; ~32% of the patients developed severe CDI and 11% developed severe-complicated CDI. The 30-day all-cause mortality rate was 11% and the 8-week recurrence rate was 9.5%. The overall mean Ct value was 32.9 (range, 23-40). Multivariable analyses showed that lower values of PCR Ct were associated with increased odds of 30-day morality (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.72-0.96) but were not independently associated with CDI severity (OR, 0.99; 95% CI, 0.90-1.09) or recurrence (OR, 0.88; 95% CI, 0.77-1.00). CONCLUSIONS: Our findings suggest that PCR Ct values at the time of diagnosis may have a limited predictive value and utility in clinical decision making for inpatients with CDI. Larger, prospective studies across different patient populations are needed to confirm our findings.

Acute infectious myelopathies.

PURPOSE OF REVIEW: The patient who presents with an acute spinal cord syndrome with weakness/paralysis of the limbs presents a diagnostic. Two important syndromes are acute transverse myelitis (ATM) and acute flaccid paralysis (AFP). Both can be caused by a number of infectious and noninfectious causes. Since 2014 there have been outbreaks of acute flaccid myelitis (a subgroup of AFP) in the United States, with a national surveillance program underway. In addition, there have been increasing reports of ATM from new and emerging pathogens, and opportunistic infections in immunocompromised hosts. RECENT FINDINGS: Infectious causes of ATM or AFP need to be ruled out first. There may be important clues to an infectious cause from epidemiologic risk factors, immune status, international travel, MRI, and laboratory findings. We summarize key features for the more common pathogens in this review. Advances in laboratory testing have improved the diagnostic yield from cerebrospinal fluid, including real-time polymerase chain reaction, metagenomic next-generation sequencing, and advanced antibody detection techniques. These tests still have limitations and require clinical correlation. SUMMARY: We present a syndromic approach to infectious myelopathies, focusing on clinical patterns that help narrow the diagnostic possibilities.

Safety issues in vasculitis: infections and immunizations in the immunosuppressed host.

Infectious diseases are a significant cause of morbidity and mortality in immunosuppressed patients, including those with connective tissue diseases. Both disease and treatment contribute to a predisposition to infection in immunocompromised patients. Significant infection and morbidity occur in 25% to 50% of these patients with a median mortality of 5.2% due to common bacterial infections, such as pneumonia or bacteremia, and opportunistic fungal infections such as Pneumocystis. The lungs, skin, urinary tract, blood, and central nervous system are commonly affected. Pathogens such as Pneumocystis jirovecii, Histoplasma capsulatum, Aspergillus species, herpes zoster, JC virus, Nocardia asteroides, and Nocardia species are increasingly prevalent in immunocompromised patients. Improved recognition, diagnosis, and prevention of these infections are needed to enhance outcomes in these patients.

Clinical presentation and management of histoplasmosis in older adults.

OBJECTIVES: To describe the influence of age on clinical features of histoplasmosis. DESIGN: Retrospective single-center cohort study. SETTING: Large tertiary care center. PARTICIPANTS: All individuals who met criteria for probable or proven histoplasmosis between 1998 and 2008. MEASUREMENTS: Participants were divided into the following categories of histoplasmosis: acute pulmonary, chronic pulmonary, asymptomatic, disseminated, and other. Correcting for immune status, the influence of age at diagnosis on presentation, diagnosis, imaging, treatment, and all-cause mortality was evaluated. RESULTS: In 347 participants with histoplasmosis, a number of characteristics were associated with age when evaluating participants according to diagnostic category. An age-associated increase in asymptomatic histoplasmosis was observed (P < .001). In symptomatic pulmonary histoplasmosis, older adults were less likely to present with chest pain (P < .001) and less likely to have hilar lymphadenopathy on imaging (P = .04). Lower rates of seropositivity with older age were seen in asymptomatic (P = .04) but not other forms of histoplasmosis. Cavitary disease was associated with older age in chronic pulmonary histoplasmosis (P = .05). Treatment did not change with age. All-cause mortality at 6 months was 4% and was associated with older age (P = .02). CONCLUSION: Although most studied characteristics of histoplasmosis were similar, notable age-related differences were present. Chronic cavitary disease and asymptomatic histoplasmosis were more common with older age. In acute histoplasmosis, the lack of chest pain and hilar lymphadenopathy may hinder diagnosis in older adults.

Methicillin-resistant Staphyloccocus aureus heel abscess: an uncommon emergency department diagnosis.

Heel abscesses present as heel pain that progressively worsens, with associated tenderness and fullness at the heel pad. Radiological studies like computed tomography, magnetic resonance imaging, or ultrasound can help correctly diagnose a heel pad abscess. Generally, these patients require i.v. antibiotics and operative management to adequately drain the abscess. It is recommended to avoid incising the plantar aspect of the heel to minimize chronic post-drainage heel pain.

Clinical utility of cytomegalovirus viral load in bronchoalveolar lavage in lung transplant recipients.

The utility of cytomegalovirus (CMV) viral load (VL) by quantitative hybrid capture assay (Q-HCA) was investigated in bronchoalveolar lavage (BAL) from lung transplant recipients and compared with BAL cultures and blood VL. Forty-three consecutive BAL samples from 27 lung transplant recipients were analyzed. All samples had shell vial (SV) cultures in addition to Q-HCA. Histopathology was done on all lung tissues, and immunohistochemistry (IHC) in those with positive CMV cultures. Fifteen (56%) lung transplant recipients had both positive BAL SV cultures and BAL VL. Five of 15 had CMV pneumonitis with a VL in BAL >500 000 copies/mL (mean: 1638 450). Ten patients without CMV pneumonitis had VL in BAL <500 000 copies/mL (mean 81 820, p = 0.002). High VL in BAL and blood invariably meant CMV pneumonitis, but 2 patients with CMV pneumonitis had high BAL VL but relatively low blood VL. Initial CMV seronegativity was associated with pneumonitis (4/5 vs. 1/10; p = 0.004) and higher BAL CMV VL (p = 0.03). High CMV BAL or blood VL did not correlate with acute rejection or development of bronchiolitis obliterans syndrome (BOS). High CMV VL in BAL in lung transplant recipients is strongly associated with CMV pneumonitis, and may be more predictive than peripheral blood viral load.

West Nile fever: lessons from the 2002 season.

West Nile fever has now spread to much of the United States. This disease can be diagnosed using one of several laboratory tests, notably an immunoglobulin M enzyme-linked immunosorbent assay. It can cause devastating neurologic damage, including an unusual polio-like syndrome. Magnetic resonance imaging is an important imaging tool in such patients. Treatment is largely supportive, although antiviral agents are under investigation.

Predictive value and cost-effectiveness analysis of a rapid polymerase chain reaction for preoperative detection of nasal carriage of Staphylococcus aureus.

OBJECTIVE: To determine the accuracy and cost-effectiveness of a polymerase chain reaction (PCR) for detecting nasal carriage of Staphylococcus aureus directly from clinical specimens. CROSS-SECTIONAL STUDY: This occurred in a tertiary-care hospital in Cleveland, Ohio, and included 239 consecutive patients who were scheduled for a cardiothoracic surgical procedure. Conventional cultures and a PCR for S. aureus from nasal swabs were used as measurements. COST-EFFECTIVENESS ANALYSIS: Data sources were market prices and Bureau of Labor Statistics. The time horizon was the maximum period for availability of culture results (3 days). Interventions included universal mupirocin therapy without testing; initial therapy, with termination if PCR negative (treat-PCR); initial therapy, with termination if culture negative (treat-culture); treat PCR-positive carriers (PCR-guided treatment); and treat culture-positive carriers (culture-guided treatment). The perspective was institutional and costs and the length of time to treatment were outcome measures. RESULTS: Sixty-seven (28%) of the 239 swabs grew S. aureus. Rapid PCR was 97.0% sensitive and 97.1% specific for the detection of S. aureus. For populations with prevalences of nasal S. aureus carriage of up to 50%, the PCR assay had negative predictive values of greater than 97%. PCR-guided treatment had the lowest incremental cost-effectiveness ratio (1.93 dollars per additional day compared with the culture strategy). Among immediate treatment strategies, treat-PCR was most cost-effective. The universal therapy strategy cost 38.19 dollars more per additional day gained with carrier identification compared with the PCR strategy. CONCLUSION: Rapid real-time PCR is an accurate, rapid, and cost-effective method for identifying S. aureus carriers for preoperative intervention.

The neuropathology of West Nile virus meningoencephalitis. A report of two cases and review of the literature.

West Nile virus (WNV) is an emerging mosquito-transmitted encephalitis virus first recognized in North America in 1999. The pathologic manifestations of WNV infection have not been well defined. This study documents the clinicopathologic features, including autopsy findings, of 2 cases: an 81-year-old man who contracted WNV infection with meningoencephalitis and a polio-like paralysis and a hospitalized 74-year-old woman with meningoencephalitis who acquired WNV through transfusion. The pathologic findings in both cases were marked by perivascular and leptomeningeal chronic inflammation, microglial nodules, and neuronophagia, predominantly involving the temporal lobes and brainstem. These findings also were present in the spinal cord, especially the lumbar region, of the patient with polio-like paralysis. In both cases, most of the inflammatory infiltrate was composed of CD3+ T lymphocytes (a predominance of CD8+ over CD4+ T cells), CD68+ macrophages, and rare CD20+ B lymphocytes. These cases further define the clinical and pathologic spectrum of central nervous system disease in WNV infection.

Actinobacillus actinomycetemcomitans endogenous endophthalmitis: report of two cases and review of the literature.

Endogenous endophthalmitis due to Actinobacillus actinomycetemcomitans is an unusual disease with serious sequelae. Of the 4 cases published in the literature only 1 recovered useful vision after treatment. This study reports on 1 additional patient and expands on the previously described brief ophthalmology case report of another patient with marked visual impairment at presentation and good visual recovery after treatment. Of the 5 patients described, 4 had pre-existing heart abnormalities, 3 had permanent pacemakers and 2 had periodontal disease. Definite endocarditis by Duke criteria was present in 3 patients. Endocarditis should be ruled out in every patient with A. actinomycetemcomitans endophthalmitis, even in the absence of systemic complaints and prior penicillin prophylaxis. Eye specimen cultures should be incubated for 10 d. A thorough dental examination should be done in each patient and any periodontal disease should be promptly treated.

Antimicrobial susceptibility of vancomycin-resistant Enterococcus faecium: potential utility of fosfomycin.

The increasing prevalence of vancomycin-resistant enterococcal (VRE) infections has necessitated a search for drugs that are effective in treating these infections, and a need to determine whether currently available antimicrobials are effective. 75 consecutive clinical isolates of vancomycin-resistant Enterococcus faecium (VRE faecium) (40 blood and 35 urine isolates) isolated over 1 y at the Cleveland Clinic Foundation were tested for susceptibility to linezolid, quinupristin-dalfopristin, fosfomycin and nitrofurantoin using the Etest. The minimum inhibitory concentrations were read independently by 3 observers and compared, and a final reading was obtained by predetermined criteria. The proportion of isolates susceptible to linezolid, quinupristin-dalfopristin, fosfomycin and nitrofurantoin was 100%, 98.7%, 98.7% and 78.7%, respectively. No single isolate was resistant to more than 1 of the 4 drugs tested. Etest presented significant unexpected difficulties in testing for VRE faecium susceptibility to nitrofurantoin. Fosfomycin may be a useful alternative to linezolid and quinupristin-dalfopristin in the treatment of VRE infections in certain clinical situations, e.g. uncomplicated urinary tract infections. In addition, the use of fosfomycin could limit the use of newer agents, thus reducing the chance of development of further resistance in the enterococci.

Endogenous endophthalmitis: an 18-year review of culture-positive cases at a tertiary care center.

A retrospective chart review of all patients seen at the Cleveland Clinic Foundation with infectious endogenous endophthalmitis between January 1982 and August 2000 revealed 34 affected eyes in 27 patients. During this time, the median incidence of endogenous endophthalmitis was 1.8 cases/year, and 48.1% of patients presented as outpatients. Twenty-six patients presented to an ophthalmologist, and the diagnosis was initially missed in almost half the cases. Eleven patients had an unremarkable physical exam except for eye findings. We found an equal incidence of bacterial and fungal endophthalmitis and a predominance of among the fungal etiologic agents. We did not, however, note a predominance of Gramnegative organisms seen mostly in reports from Asia. The microbiologic diagnosis was based on aqueous and vitreous cultures or positive eye histopathology stains in almost two-thirds of cases. The sensitivity of the Gram stain was poor, but its specificity and positive predictive value were excellent. The vitreous cultures obtained by vitrectomy instruments were more sensitive in making the diagnosis than the vitreous needle biopsy. Aside from blood cultures and eye specimen cultures, half the patients had an additional infectious focus, most frequently a urinary tract infection, whereas infectious endocarditis was seen in a small minority. Twelve patients had visual improvement with treatment with a final visual acuity better than 20/200 in 44% of the eyes. Good visual outcome was associated with visual acuity of 20/200 or better at diagnosis and with the absence of hypopyon.

Identification of Histoplasma capsulatum from culture extracts by real-time PCR.

We designed and tested a real-time LightCycler PCR assay for Histoplasma capsulatum that correctly identified the 34 H. capsulatum isolates in a battery of 107 fungal isolates tested and also detected H. capsulatum in clinical specimens from three patients that were culture positive for this organism.