Surveillance for Healthcare-Associated Infections: Hospital-Onset Adult Sepsis Events Versus Current Reportable Conditions.

BACKGROUND: US hospitals are required by the Centers for Medicare and Medicaid Services to publicly report central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), Clostridioidesdiffficile, methicillin-resistant Staphylococcus aureus bacteremia, and selected surgical site infections for benchmarking and pay-for-performance programs. It is unclear, however, to what extent these conditions capture the full breadth of serious healthcare-associated infections (HAIs). The Centers for Disease Control and Prevention's (CDC's) hospital-onset Adult Sepsis Event (HO-ASE) definition could facilitate more comprehensive and efficient surveillance for serious HAIs, but the overlap between HO-ASE and currently reportable HAIs is unknown. METHODS: We retrospectively assessed the overlap between HO-ASEs and reportable HAIs among adults hospitalized between June 2015-June 2018 in 3 hospitals. Medical record reviews were conducted for 110 randomly selected HO-ASE cases to determine clinical correlates. RESULTS: Among 282 441 hospitalized patients, 2301 (0.8%) met HO-ASE criteria and 1260 (0.4%) had reportable HAIs. In-hospital mortality rates were higher with HO-ASEs than reportable HAIs (28.6% vs 12.9%). Mortality rates for HO-ASE missed by reportable HAIs were substantially higher than mortality rates for reportable HAIs missed by HO-ASE (28.1% vs 6.3%). Reportable HAIs were only present in 334/2301 (14.5%) HO-ASEs, most commonly CLABSIs (6.0% of HO-ASEs), C. difficile (5.0%), and CAUTIs (3.0%). On medical record review, most HO-ASEs were caused by pneumonia (39.1%, of which only 34.9% were ventilator-associated), bloodstream infections (17.4%, of which only 10.5% were central line-associated), non-C. difficile intra-abdominal infections (14.5%), urinary infections (7.3%, of which 87.5% were catheter-associated), and skin/soft tissue infections (6.4%). CONCLUSIONS: CDC's HO-ASE definition detects many serious nosocomial infections missed by currently reportable HAIs. HO-ASE surveillance could increase the efficiency and clinical significance of surveillance while identifying new targets for prevention.

Extended spectrum ß-lactamase-producing Enterobacteriaceae infection in heart and lung transplant recipients and in mechanical circulatory support recipients.

BACKGROUND: Extended spectrum ß-lactamase (ESBL)-producing gram-negative bacilli are increasingly reported in patients with a variety of risk factors including prior cephalosporin and antibiotic usage, prolonged hospitalizations, existence of comorbid conditions, and critical illness. METHODS: Retrospective review of infections caused by ESBL-producing Enterobacteriaceae was performed in heart transplant (HTx), lung transplant (LTx), and mechanical circulatory support (MCS) device recipients at a large transplant center. RESULTS: Among 1065 patients transplanted/implanted, the incidence of ESBL-related infections (bacteremia, urinary tract infections, pneumonia, central venous catheter-associated infection, and wound infections) in HTx, LTx, and MCS device recipients was reported at 2.2%, 5.5%, and 10.7%, respectively, caused by ESBL-producing Klebsiella pneumoniae, Escherichia coli, Klebsiella oxytoca, and Citrobacter freundii. CONCLUSIONS: Early detection and adequate duration of therapy for ESBL-producing Enterobacteriaceae in solid organ transplants and MCS device recipients are essential in successful patient outcomes including prevention of recurrent infection.

Necrotizing Fasciitis Associated with Staphylococcus lugdunensis.

Necrotizing fasciitis is a life-threatening soft tissue infection that results in rapid local tissue destruction. Type 1 necrotizing fasciitis is characterized by polymicrobial, synergistic infections that are caused by non-Group A streptococci, aerobic and anaerobic organisms. Type 2 necrotizing fasciitis involves Group A Streptococcus (GAS) with or without a coexisting staphylococcal infection. Here we provide the first report of necrotizing fasciitis jointly associated with the microbes Group B Streptococcus and Staphylococcus lugdunensis. S. lugdunensis is a commensal human skin bacterium known to cause often painful and prolonged skin and soft tissue infections. To our knowledge, however, this is the first case of Staph. lugdunensis-associated necrotizing fasciitis to be reported in the literature.

Use of hearts transplanted from donors with severe sepsis and infectious deaths.

BACKGROUND: The reluctance to use organs from donors who have died from severe infections is based on the potential transmission of an infectious agent to the recipient and on the uncertainty about allograft function in the setting of severe donor sepsis. METHODS: From 1999 to 2007, donor hospital records were reviewed which focused on microbiology cultures and sensitivity results; type and duration of antimicrobial therapy; hemodynamic data, results of echocardiogram, and imaging studies. Preliminary positive and negative results from pre-harvest blood, respiratory, urine, and cerebrospinal fluid cultures were verified with the procurement agency. The harvesting surgeon performed gross inspection of donor valvular structures. RESULTS: Nine donor hearts were transplanted from patients who expired from community onset infections with severe septic shock, meningitis, and/or pneumonia caused by Streptococcus pneumoniae (n = 4), Streptococcus milleri (n = 2), Neisseria meningitidis (n = 2), and unidentified gram- positive cocci (n = 1). Four donors had probable infection-induced intracranial hemorrhage, and all donors were vasopressor-dependent before organ procurement. No evidence of donor-transmitted infection, sepsis, or rejection was observed, and long-term function remained excellent; allograft dysfunction in three patients resolved after transplant. Our series of nine donors represents approximately 1.3% of successfully transplanted cardiac allografts during the respective period of review. CONCLUSIONS: Patients succumbing to severe infections (meningitis, pneumonia, and septic shock) should not be arbitrarily excluded for possible heart donation. Assessing the suitability of donors with severe infections requires flawless communication between the donor and transplant facility, including a comprehensive evaluation of donor infection and pathogen(s), severity of sepsis, adequacy of antimicrobial treatment, and the degree of sepsis-induced myocardial dysfunction.

A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575.

OBJECTIVE: To assess phenotype susceptibility testing (PHENO) with standard of care (SOC) to improve antiretroviral therapy. DESIGN: A prospective, multicenter study of 238 patients taking a stable antiretroviral regimen for > 6 months, with one or two protease inhibitors (PI) and entry HIV RNA > 400 copies/ml. METHOD: Patients were randomized to receive or not receive PHENO results for selecting antiretroviral regimens. Primary outcome was HIV RNA measures. RESULTS: At baseline, median CD4 cell count was 277 x 10 cells/l and HIV RNA was 10 000 copies/ml; 76% had not taken a non-nucleoside reverse transcriptase inhibitor drug (NNRTI). There were significant differences between the groups in selection of baseline nucleoside reverse transcriptase inhibitor (NRTI). At month 6, reduction in HIV RNA was 0.71 and 0.69 log10 copies/ml for PHENO and SOC, respectively; the proportion with < 400 copies/ml (48%) was the same for both groups. No differences were seen at month 12. In a subgroup with resistance to four or more PI, 50% of the PHENO versus 17% of the SOC had HIV RNA < 400 copies/ml at month 6 (P = 0.02). The number of NNRTI and PI, but not NRTI, in the regimen that were active by phenotype at baseline was a strong independent predictor of viral suppression (P < 0.006). Use of alternative NRTI sensitivity cut-offs improved their predictive value. CONCLUSIONS: Although virological outcome was similar in both groups, the potential benefit of PHENO was seen in patients with more resistant virus. Lack of appropriate cut-offs may have partially accounted for the lack of benefit from PHENO and demonstrated the need to identify clinically relevant sensitivity cut-off points.

Corynebacterium jeikeium sepsis after 8-methoxypsolaren photopheresis for cutaneous T-cell lymphoma.

We describe a patient with cutaneous T-cell lymphoma who developed Corynebacterium jeikeium sepsis after experimental treatment with 8-methoxypsolaren. The epidemiology and clinical features of C. jeikeium infection are discussed. The patient was successfully treated with intravenous vancomycin without recurrence.

The clinical relevance of non-nucleoside reverse transcriptase inhibitor hypersusceptibility: a prospective cohort analysis.

OBJECTIVE: To evaluate the clinical significance of hypersusceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI). DESIGN: Analysis of a prospective clinical trial cohort. PATIENTS: NNRTI-naive patients failing a stable antiretroviral regimen. MEASUREMENTS: HIV phenotype, HIV RNA, and CD4 cell counts were prospectively collected after patients changed to a new regimen. Hypersusceptibility to NNRTI was defined as a fold-change (FC) in IC50 (inhibitory concentration of 50%) of < 0.4. RESULTS: The 177 patients had a mean HIV RNA of 4.1 log10 copies/ml, CD4 cell count of 322 x 10(6) cells/l and 41 months of prior antiretroviral treatment. Hypersusceptibility to one or more NNRTI was present in 29%. Both longer duration and reduced susceptibility to nucleoside reverse transcriptase inhibitors were associated with efavirenz hypersusceptibility (P < 0.05). NNRTI-containing regimens were initiated in 106 patients at baseline. The mean change in log HIV RNA after 6 months was greater for patients with hypersusceptibility (-1.2 log10 copies/ml; n = 21) than in patients without (-0.8 log10 copies/ml; n = 77) (P = 0.016). Differences persisted to month 12 (P = 0.023). Multiple linear regression models confirmed that hypersusceptibility to NNRTI was a significant independent predictor of the magnitude of early (months 1-4) HIV RNA reduction, after accounting for the baseline HIV RNA and the number of drugs to which the patient's virus was susceptible (P < 0.02). CD4 cell increases (months 4-10) were 28- 60 x 10(6) cells/l greater in patients with hypersusceptible virus (P < or = 0.1). CONCLUSION: NNRTI hypersusceptibility occurred in more than 20% of nucleoside-experienced patients and was associated with greater reduction of HIV RNA and increase in CD4 cells.

Immune Reconstitution Strategies in HIV.

Although potent antiretroviral therapy can dramatically decrease HIV replication and improve some aspects of host immunity, incomplete immune reconstitution persists even after several years of fully suppressive therapy. In addition, long-term toxicities of antiretroviral medications and the probability of developing multidrug-resistant virus with long-term use indicate that alternate means of controlling viral replication are needed for more durable suppression of HIV. Immune-based therapies may help potentiate the host's own defenses against HIV and other pathogens, and may ultimately result in more durable viral suppression and lower incidence of antiretroviral therapy-related side effects and toxicities.