Talaromyces marneffei infection in a non-HIV non-endemic population.

Introduction: Talaromyces marneffei infection is a systemic mycosis, caused by a dimorphic fungus, an opportunistic pathogen formerly known as Penicillium marneffei. This disease is endemic to Southeast Asia and common in human immunodeficiency virus (HIV) infected patients with low CD4 counts. Here we present a very rarely reported case of Talaromyces marneffei infection in an apparent non-immunosuppressed patient presenting decades later in a non-endemic setting (United States). Presentation of case: Our patient was a 75-year-old Caucasian Navy veteran, who served in Vietnam as a part of the Swift Boat service in 1966. He presented to his primary care provider with uncontrolled nonproductive cough and abnormal chest computerized tomography. Bronchoscopy specimens showed Talaromyces. He was empirically treated with itraconazole and then switched to voriconazole after confirmation of diagnosis but he later deteriorated was changed to liposomal amphotericin B and isavuconazole. Patient did well for the next 90 days on isavuconazole until the therapy was stopped. Soon after stopping the medication (isavuconazole) his symptoms recurred and ultimately patient expired. Discussion: Talaromycosis generally presents as pulmonary infection with manifestations similar with other endemic fungi. It is often seen HIV patients with travel to South east Asia. Very rarely this infection is seen and reported in non-immunosuppressed and in non-endemic areas. To date there are 4 well-documented cases among non-HIV, non-endemic population. Conclusion: Talaromyces can cause infection in non-HIV and non-endemic population and could be an underrecognized cause of pulmonary infections among veterans with even a remote history of exposure to the organism during deployment.

Multicenter evaluation of the clinical outcomes of daptomycin with and without concomitant ß-lactams in patients with Staphylococcus aureus bacteremia and mild to moderate renal impairment.

Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of ß-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant ß-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a ß-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with ß-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.

Prospective comparison of methicillin-susceptible and methicillin-resistant community-associated Staphylococcus aureus infections in hospitalized patients.

BACKGROUND: We sought to determine the proportion of community-associated Staphylococcus aureus infections due to methicillin-resistant S. aureus (CA-MRSA) at a large county hospital. In addition, we sought to identify the demographic and clinical risk factors associated with CA-MRSA infection. METHODS: Patients were prospectively enrolled if they were admitted to Parkland Hospital and had a positive culture for S. aureus isolated within 72 h of admission. The patients were interviewed using a standardized data questionnaire. Data collected included patient demographics, clinical history, as well as health care and non-health care associated MRSA risk factors. Bacterial susceptibilities were verified through review of microbiology laboratory and pharmacy records. Isolates were tested for Panton-Valentine leukocidin (PVL) gene, SCCmec type, and for inducible clindamycin resistance. RESULTS: One hundred and ninety-eight patients were interviewed prospectively, of which eight had colonization without active infection. One hundred and nineteen patients were infected with MRSA and 71 patients were infected with methicillin-susceptible S. aureus (MSSA). Patients with MRSA were more likely to be African-American and unemployed. Patients with MRSA most commonly presented with a skin or soft tissue infection (SSTI): 69% versus 45%, p=0.0012, while patients with MSSA were more likely to have infection of the respiratory tract: 11% versus 3%, p=0.02. Patients with MRSA were more likely to have used antibiotics in the past six months, been homeless, have a history of incarceration, have abused alcohol and have a history of infection with MRSA. In multivariate analysis, African-American race, antibiotics in the past six months, and a history of being homeless were associated with MRSA infection. Only 11 of 119 (9%) MRSA patients did not have at least one of these risk factors. PVL gene was present in 72 of 74 (97%) MRSA isolates and SCCmec type IV was present in 63 of 75 (84%) MRSA isolates. CONCLUSIONS: The majority of patients hospitalized with community-associated S. aureus infections were due to MRSA, most of which involved an SSTI. African-American race, recent antibiotics and past homeless status predicted infection with MRSA; however, no clinical profile could reliably exclude MRSA. Clinicians should be aware of the increasing prevalence of CA-MRSA.

Investigational new drugs for the treatment of resistant pneumococcal infections.

Antibiotic resistance in Streptococcus pneumoniae is not only increasing with penicillin but also with other antimicrobial classes including the macrolides, tetracyclines and sulfonamides. This trend with antibiotic resistance has highlighted the need for the further development of new anti-infectives for the treatment of pneumococcal infections, particularly against multi-drug resistant pneumococci. Several new drugs with anti-pneumococcal activity are at various stages of development and will be discussed in this review. Two new cephalosporins with activity against S. pneumoniae include ceftobiprole and RWJ-54428. Faropenem is in a new class of beta-lactam antibiotics called the penems. Structurally, the penems are a hybrid between the penicillins and cephalosporins. Sitafloxacin and garenoxacin are two new quinolones that are likely to have a role in treating pneumococcal infections. Oritavancin and dalbavancin are glycopeptides with activity against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus spp. as well as multi-drug resistant pneumococci. Tigecycline is the first drug in a new class of anti-infectives called the glycycyclines that has activity against penicillin-resistant pneumococci.