James E. Peacock

The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance

OBJECTIVES To assess the changing epidemiology of candidemia in the 1990s, to evaluate the clinical implications for the presence of non-Candida albicans in blood, and to evaluate the presence of antifungal resistance in relation to prior antifungal administration. DESIGN Multicenter prospective observational study of patients with positive blood cultures for Candida species or Torulopsis glabrata. SETTING Four tertiary care medical centers. RESULTS Four hundred twenty-seven consecutive patients were enrolled. The frequency of candidemia due to non-C. albicans species significantly increased in each hospital throughout the 3.5-year study period (P = 0.01). Thirteen percent of candidemias occurred in patients who were already receiving systemic antifungal agents. Candidemias developing while receiving antifungal therapy were more likely caused by non-C. albicans species than by C. albicans species (P = 0.0005). C. parapsilosis and C. krusei were more commonly seen with prior fluconazole therapy, whereas T. glabrata was more commonly seen with prior amphotericin B therapy. Candida species isolated during episodes of breakthrough candidemia exhibited a significantly higher MIC to the antifungal agent being administered (P < 0.001). CONCLUSION In this large scale study, the non-C. albicans species, especially T. glabrata, emerged as important and frequent pathogens causing fungemia. This finding has major clinical implications given the higher complication and mortality rate associated with the non-C. albicans species. The change in the pattern of candidemia might be partly attributed to the increase in number of immunocompromised hosts and the widespread use of prophylactic or empiric antifungal therapy. This is an ominous sign given the in vitro resistance of the non-C. albicans species to currently available antifungal agents.

Staphylococcus aureus Bacteremia Recurrence and the Impact of Antibiotic Treatment in a Prospective Multicenter Study

Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as β-lactam antibiotics, an assumption that remains open to debate.We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse.Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.

Methicillin-Resistant Staphylococcus aureus: Introduction and Spread Within a Hospital

In March 1978, a strain of methicillin-resistant Staphylococcus aureus was introduced from the community into a university hospital. Within 6 months of admission of the index case, methicillin-resistant S. aureus was isolated from 30 additional patients, 22 of whom were epidemiologically linked by a common phage type (6/47/54/75/83A) and roommate-to-roommate spread. Sixteen of 31 cases were infected, six with bacteremia. Patients with infections received cephalosporins more frequently before infection than did control subjects (p < 0.05). Patients acquiring methicillin-resistant S. aureus in the intensive care unit had a longer mean stay, had higher overall mortality, and received nafcillin and aminoglycosides more frequently than did cohorted control subjects. By mid-1979, methicillin-resistant S. aureus accounted for 38%, 31%, and 24% of all nosocomial S. aureus postoperative wound, pulmonary, and bloodstream infections, respectively. In hospitals with significant methicillin-resistant S. aureus isolation rates, initial empiric therapy of presumed S. aureus infection with vancomycin seems warranted.

A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance.

Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis.We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%.Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate awnd multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia.Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram.Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.Abstract: Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis. We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%. Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate awnd multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia. Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram. Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.

Pseudallescheria boydii Brain Abscess Successfully Treated with Voriconazole and Surgical Drainage: Case Report and Literature Review of Central Nervous System Pseudallescheriasis

Pseudallescheria boydii and its asexual form, Scedosporium apiospermum, are ubiquitous, saprophytic fungi that commonly cause cutaneous infection. However, in certain circumstances, P. boydii can also cause invasive disease, which can involve the central nervous system (CNS). When the CNS becomes involved, treatment is difficult, therapeutic options are limited, and the prognosis is poor. We report a case of Pseudallescheria brain abscess successfully treated with surgical drainage and systemic voriconazole, the first such case to be described in the literature. We also review previously reported cases of CNS pseudallescheriasis and evaluate therapeutic options.

Fitbit®: An accurate and reliable device for wireless physical activity tracking.

Background: A smart accelerometer named the Fitbit has recently been introduced in the consumer market as a physical activity monitor that can interface wirelessly with mobile phones and a manufacturer-established website to allow consumers to track their physical activity in real-time. The purpose of this study was to examine the validity and reliability of the Fitbit for measuring energy expenditure during treadmill walking and running relative to energy expenditure assessed by indirect calorimetry. Methods: A total of 23 healthy adults (10 males, mean age: 30.6 ± 7.9 years; mean BMI: 24.7 ± 3.0 kg/m2) completed a four-phase treadmill exercise protocol (6 min/phase) under laboratory conditions. The protocol consisted of walking at slow (1.9 mph), moderate (3.0 mph), and brisk (4.0 mph) paces; and jogging (5.2 mph). Participants were fitted with three hip-based Fitbit One devices (two on right, one on left hip) and two wrist-based Fitbit Flex devices (one on right and left wrist). Energy expenditure was ...

Infectious emergencies in patients with diabetes mellitus

Although it remains controversial as to whether diabetics have an overall increased incidence of infection as compared to nondiabetics, several potentially life-threatening infections do appear to be uniquely associated with diabetes. These infections generally occur in older diabetics with less than optimal glucose control. For each entity, selected symptoms and signs may suggest the diagnosis but confirmation of via tissue biopsy with culture and histopathology or radiography is usually necessary. Management typically require both antimicrobial treatment and surgery.

Timing of the most recent device procedure influences the clinical outcome of lead-associated endocarditis results of the MEDIC (Multicenter Electrophysiologic Device Infection Cohort).

OBJECTIVES The purpose of this study was to determine whether the timing of the most recent cardiac implantable electronic device (CIED) procedure, either a permanent pacemaker or implantable cardioverter-defibrillator, influences the clinical presentation and outcome of lead-associated endocarditis (LAE). BACKGROUND The CIED infection rate has increased at a time of increased device use. LAE is associated with significant morbidity and mortality. METHODS The clinical presentation and course of LAE were evaluated by the MEDIC (Multicenter Electrophysiologic Device Cohort) registry, an international registry enrolling patients with CIED infection. Consecutive LAE patients enrolled in the Multicenter Electrophysiologic Device Cohort registry between January 2009 and May 2011 were analyzed. The clinical features and outcomes of 2 groups were compared based on the time from the most recent CIED procedure (early, <6 months; late, >6 months). RESULTS The Multicenter Electrophysiologic Device Cohort registry entered 145 patients with LAE (early = 43, late = 102). Early LAE patients presented with signs and symptoms of local pocket infection, whereas a remote source of bacteremia was present in 38% of patients with late LAE but only 8% of early LAE (p < 0.01). Staphylococcal species were the most frequent pathogens in both early and late LAE. Treatment consisted of removal of all hardware and intravenous administration of antibiotics. In-hospital mortality was low (early = 7%, late = 6%). CONCLUSIONS The clinical presentation of LAE is influenced by the time from the most recent CIED procedure. Although clinical manifestations of pocket infection are present in the majority of patients with early LAE, late LAE should be considered in any CIED patient who presents with fever, bloodstream infection, or signs of sepsis, even if the device pocket appears uninfected. Prompt recognition and management may improve outcomes.

Unmasking masked hypertension: prevalence, clinical implications, diagnosis, correlates and future directions

‘Masked hypertension’ is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15–30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared with sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment and areas for future research.

Persistent neutrophilic meningitis: Report of four cases and review of the literature

Persistent neutrophilic meningitis is a poorly described variant of chronic meningitis characterized by the persistence of neutrophils in the CSF over extended periods of time (greater than 1 wk) in association with ongoing signs of meningeal inflammation and negative CSF cultures for bacteria and other pathogens. Although the incidence of persistent neutrophilic meningitis is difficult to ascertain, a review of available literature on CNS infections suggests that this entity is not rare. Etiologies of this syndrome are both infectious and noninfectious. Among infectious causes, bacteria such as Nocardia and Actinomyces and systemic mycoses such as Aspergillus and the zygomycetes are the predominant pathogens. The pathogenesis of the persistent neutrophilic CSF response is unknown; with some infectious etiologies, there may be a correlation between neutrophil response and the morphology of the invading organism. Mycelial-like pathogens appear to be the primary stimulus for an ongoing neutrophilic inflammatory response. In cases of persistent neutrophilic meningitis, epidemiologic features and clinical setting frequently offer clues to the etiologic agent, especially in the immunocompromised host. Evaluation should include repetitive cultural and serologic studies of the CSF with special emphasis upon special cultural methods, antigen detection and detection of characteristic metabolic byproducts. Biopsy of extraneural sites of disease should be pursued whenever possible to provide data for an inferential diagnosis of CNS disease. CNS biopsies should be selectively performed in those patients undergoing craniotomy for evaluation of mass lesions. Therapy must be individualized. However, in the immunocompromised host, consideration should be given to the empiric use of amphotericin B with or without a sulfonamide in undiagnosed cases that manifest progressive clinical deterioration.