Yoav Golan

Cat scratch disease (CSD), caused by Bartonella henselae, usually presents as regional lymphadenopathy/lymphadenitis, known as typical CSD or as atypical CSD, which includes, among others, neurological manifestations. Serology for anti-B. henselae IgG antibodies is the most commonly used diagnostic tests for CSD. Intravenous immunoglobulin (IVIG) is given for an increasing number of medical conditions and may cause interference with serological testing. We report six patients with neurological manifestations and two patients with Kawasaki disease mimicking typical CSD, mistakenly diagnosed as CSD due to false-positive serology following IVIG therapy. Bartonella IgG serology was positive one to six days after IVIG administration and reverted to negative in seven of eight patients or significantly decreased (1 patient) ≤30 days later. In patients with CSD, IgG titers remained essentially unchanged 15–78 days after the positive serum sample. An additional eight patients treated with IVIG for various conditions were evaluated prospectively. All were seronegative one day pre-IVIG infusion, five patients demonstrated an increase in the IgG titers one to three days after IVIG administration, one interpreted as positive and four as intermediate, whereas three patients remained seronegative, suggesting that false seropositivity after IVIG therapy may not occur in all patients. Treatment with IVIG can result in false-positive serology for B. henselae. Increased awareness to the misleading impact of IVIG is warranted to avoid misinterpretation. Repeat testing can distinguish between true and false serology. Preserving serum samples prior to IVIG administration is suggested.

Despite the increasing availability of antibiotics with activity against pathogens that cause community-acquired pneumonia (CAP), CAP remains a major cause of morbidity, hospital admissions and re-...

Acute bacterial skin and skin-structure infections (ABSSSIs) are a common reason for seeking care at acute healthcare facilities, including emergency departments. Staphylococcus aureus is the most common organism associated with these infections, and the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) has represented a considerable challenge in their treatment. To address this need, a number of new antibiotics have been developed for the treatment of ABSSSIs in the past several years. Most of these agents focus primarily on gram-positive organisms, particularly MRSA; however, there has not been an oral agent that can reliably treat MRSA, as well as relevant gram-negative pathogens. Acute skin infections that involve mixed gram-positive and gram-negative pathogens must also be considered as they can be associated with discordant antimicrobial therapy. Here, I review ABSSSI treatment guidelines in the hospital setting and discuss current and future antibiotic options for treatment of this commonly encountered infection.

Empiric therapy for healthcare-associated infections remains challenging, especially with the continued development of Gram-negative organisms producing extended-spectrum β-lactamases (ESBLs) and the threat of multi-drug–resistant organisms. Current treatment options for resistant Gram-negative infections include carbapenems, tigecycline, piperacillin-tazobactam, cefepime, ceftazidime, and two recently approved therapies, ceftolozane-tazobactam and ceftazidime-avibactam. This systematic literature review surveys the published clinical trial evidence available since 2000 in support of both current and emerging treatment options in the settings of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI). When available, clinical cure rates for patients with infections from ESBL-producing strains are provided, as is information about efficacy against Pseudomonas aeruginosa. Clinical trial evidence to guide selection of empiric antibiotic therapy in patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs is limited. Though most of the clinical trials explored in this overview enrolled patients with complicated infections, often patients with severe infections and multiple comorbidities were excluded. Practitioners in the clinical setting who are treating patients with complicated, hospital-acquired, Gram-negative IAIs and UTIs need to consider the possibility of polymicrobial infections, antibiotic-resistant organisms, and/or severely ill patients with multiple comorbidities. There is a severe shortage of evidence-based research to guide the selection of empiric antibiotic therapy for many patients in this setting. New therapies recently approved or in late-stage development promise to expand the number of options available for empiric therapy of these hospital-acquired, Gram-negative infections.

Clostridium difficile infection (CDI) continues to be a frequent and potentially severe infection. There is currently no validated clinical tool for use at the time of CDI diagnosis to categorize patients in order to predict response to therapy.

Clostridium difficile is currently the most important cause of infectious diarrhea in the United States. Fidaxomicin, a macrolide antibiotic, was recently approved for treatment of C. difficile infections (CDIs). In vitro studies demonstrate that fidaxomicin has a narrow spectrum of activity against C. difficile with minimal effect on the gut flora. Clinical trials indicate that fidaxomicin is as effective as vancomycin for treatment of CD with fewer recurrences. Additionally, fidaxomicin has minimal systemic absorption with few adverse side effects. Thus, fidaxomicin is an attractive new alternative for treatment of CDI.

Background. Increased mortality, treatment failure, and hospital length of stay have been reported in patients treated with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia when their isolates have a vancomycin minimum inhibitory concentration (MIC) > 1 μg/mL. Automated testing often fails to identify these isolates. We developed a simple clinical rule to predict vancomycin MIC of 2 μg/mL in patients with MRSA bacteremia. Methods. This cohort study was conducted at a tertiary care hospital and an affiliated acute rehabilitation facility. Consecutive patients with MRSA bacteremia from 2001 through 2007 were prospectively identified. Patient characteristics were examined for their association with high vancomycin MIC and a predictive model was created. Results. A total of 296 MRSA bacteremic episodes among 272 patients were identified; 19% of the episodes had isolates with a vancomycin MIC of 2 μg/mL. Variables associated with a vancomycin MIC of 2 μg/mL included older age (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.5–10.4); prior vancomycin (OR, 3.8; 95% CI, 1.9–7.6) or daptomycin (OR, 7.9; 95% CI, 1.8–34.0) exposure; the presence of a nontunneled central venous catheter (OR, 1.9; 95% CI, 1.1–3.4) or prosthetic heart valve (OR, 3.6; 95% CI, 1.3–10.0); a history of MRSA bacteremia (OR, 3.0; 95% CI, 1.6–5.6); and the presence of sepsis (OR, 2.7; 95% CI, 1.4–5.1) or shock (OR, 2.2; 95% CI, 1.1–4.2) at the time of culture. The final predictive rule included age > 50 years (3 points), prior vancomycin exposure (2 points), history of MRSA bacteremia (2 points), history of chronic liver disease (2 points), and presence of a nontunneled central venous catheter (1 point). A score cutoff of ≥ 4 resulted in a sensitivity of 75% and specificity of 59% (negative predictive value, 91%; positive predictive value, 30%). Conclusions. Several factors that predict high vancomycin MIC were identified, and a simple predictive tool was created to help clinicians determine which patients are likely to have MRSA isolates with high vancomycin MIC.

Prior analyses suggest that empiric fluconazole for ICU patients with sepsis is cost-effective. Using updated estimates of efficacy and cost, Zilberberg and colleagues compare the use of micafungin with that of fluconazole. The authors conclude that micafungin is an attractive alternative to fluconazole. This conclusion is driven by recent reduction in micafungin's cost and by better activity of micafungin against azole-resistant Candida species. Their results are limited by inflated estimates of efficacy, life expectancy and risk of Candida sepsis. This commentary explores the rationale for early anti-Candida strategies in the ICU and highlights the contribution and limitations of the article by Zilberberg and colleagues.