Diagnosis of Chagasic Encephalitis by Sequencing of 28S rRNA Gene.

We report a case of chagasic encephalitis diagnosed by 28S rRNA sequencing. The diagnosis of chagasic encephalitis is challenging, given the broad differential diagnosis for central nervous system lesions in immunocompromised patients and low sensitivity of traditional diagnostics. Sequencing should be part of the diagnostic armamentarium for potential chagasic encephalitis.

Reducing risk of Clostridium difficile infection and overall use of antibiotic in the outpatient treatment of urinary tract infection.

BACKGROUND: Risk of community-acquired Clostridium difficile infection (CA-CDI) following antibiotic treatment specifically for urinary tract infection (UTI) has not been evaluated. METHODS: We conducted a nested case-control study at Kaiser Permanente Northern California, 2007-2010, to assess antibiotic prescribing and other factors in relation to risk of CA-CDI in outpatients with uncomplicated UTI. Cases were diagnosed with CA-CDI within 90 days of antibiotic use. We used matched controls and confirmed case-control eligibility through chart review. Antibiotics were classified as ciprofloxacin (most common), or low risk (nitrofurantoin, sulfamethoxazole/trimethoprim), moderate risk, or high risk (e.g. cefpodoxime, ceftriaxone, clindamycin) for CDI. We computed the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship of antibiotic treatment for uncomplicated UTI and history of relevant gastrointestinal comorbidity (including gastrointestinal diagnoses, procedures, and gastric acid suppression treatment) with risk of CA-CDI using logistic regression analysis. RESULTS: Despite the large population, only 68 cases were confirmed with CA-CDI for comparison with 112 controls. Female sex [81% of controls, adjusted odds ratio (OR) 6.3, CI 1.7-24), past gastrointestinal comorbidity (prevalence 39%, OR 2.3, CI 1.1-4.8), and nongastrointestinal comorbidity (prevalence 6%, OR 2.8, CI 1.4-5.6) were associated with increased CA-CDI risk. Compared with low-risk antibiotic, the adjusted ORs for antibiotic groups were as follows: ciprofloxacin, 2.7 (CI 1.0-7.2); moderate-risk antibiotics, 3.6 (CI 1.2-11); and high-risk antibiotics, 11.2 (CI 2.4-52). CONCLUSIONS: Lower-risk antibiotics should be used for UTI whenever possible, particularly in patients with a gastrointestinal comorbidity. However, UTI can be managed through alternative approaches. Research into the primary prevention of UTI is urgently needed.

Q148N, a Novel Integrase Inhibitor Resistance Mutation Associated with Low-Level Reduction in Elvitegravir Susceptibility.

The integrase strand transfer inhibitor (INSTI)-resistance mutations Q148H/K/R are arguably the most important INSTI-resistance mutations as they represented the first step to high-level dolutegravir cross-resistance. We describe an individual with transmitted four-class drug resistance whose virus sequence had the previously uncharacterized mutation Q148N. Infectious molecular HIV-1 clones containing Q148N alone and in combination with G140S demonstrated ∼2.4-4.5 reduced elvitegravir susceptibility depending on the virus's genetic context but retained susceptibility to raltegravir and dolutegravir. This level of reduced elvitegravir susceptibility is lower than that observed with Q148H/K/R and in fact the infected individual responded to an initial treatment regimen containing tenofovir/emtricitabine/elvitegravir/cobicistat. Q148N was associated with a higher replication capacity than Q148H, suggesting that this mutation may be more fit in the absence of selective INSTI therapy.