The Penn Medicine COVID-19 Therapeutics Committee-Reflections on a Model for Rapid Evidence Review and Dynamic Practice Recommendations During a Public Health Emergency.

The Penn Medicine COVID-19 Therapeutics Committee-an interspecialty, clinician-pharmacist, and specialist-front line primary care collaboration-has served as a forum for rapid evidence review and the production of dynamic practice recommendations during the 3-year coronavirus disease 2019 public health emergency. We describe the process by which the committee went about its work and how it navigated specific challenging scenarios. Our target audiences are clinicians, hospital leaders, public health officials, and researchers invested in preparedness for inevitable future threats. Our objectives are to discuss the logistics and challenges of forming an effective committee, undertaking a rapid evidence review process, aligning evidence-based guidelines with operational realities, and iteratively revising recommendations in response to changing pandemic data. We specifically discuss the arc of evidence for corticosteroids; the noble beginnings and dangerous misinformation end of hydroxychloroquine and ivermectin; monoclonal antibodies and emerging viral variants; and patient screening and safety processes for tocilizumab, baricitinib, and nirmatrelvir-ritonavir.

Impact of measurement and feedback on chlorhexidine gluconate bathing among intensive care unit patients: A multicenter study.

OBJECTIVE: To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs). DESIGN: A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods). SETTING: The study was conducted across 7 geographically diverse ICUs with routine CHG bathing. PARTICIPANTS: Adult patients in the medical ICU. METHODS: CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations. RESULTS: We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001). CONCLUSIONS: Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

Survey to determine the relative importance of clinical factors used to make empiric antibiotic decisions.

A cross-sectional survey study of inpatient prescribers in a university health system was performed to assess the importance they place on different clinical risk factors when making empiric antibiotic decisions. Our findings show that these clinical risk factors were weighted differently based on the clinical scenario and the type of prescriber.

Corynebacterium propinquum endocarditis: a confounding presentation of a rare entity.

Infective endocarditis is rarely caused by Corynebacterium species. We report a unique case of Corynebacterium propinquum endocarditis in an otherwise healthy individual, and it is the first example of this organism causing culture-negative endocarditis. Conflicting clinical and microbiological data led to the use of sequencing to confirm the causative organism. This case illustrates C. propinquum as a cause of infective endocarditis, and it demonstrates the utility of ancillary molecular diagnostic techniques to identify etiologic agents in difficult cases of infective endocarditis.

The Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Colonization and Infection among Long-Term Acute Care Hospital Residents.

OBJECTIVE An improved understanding of carbapenem-resistant Klebsiella pneumoniae (CRKP) in long-term acute care hospitals (LTACHs) is needed. The objective of this study was to assess risk factors for colonization or infection with CRKP in LTACH residents. METHODS A case-control study was performed at a university-affiliated LTACH from 2008 to 2013. Cases were defined as all patients with clinical cultures positive for CRKP and controls were those with clinical cultures positive for carbapenem-susceptible K. pneumoniae (CSKP). A multivariate model was developed to identify risk factors for CRKP infection or colonization. RESULTS A total of 222 patients were identified with K. pneumoniae clinical cultures during the study period; 99 (45%) were case patients and 123 (55%) were control patients. Our multivariate analysis identified factors associated with a significant risk for CRKP colonization or infection: solid organ or stem cell transplantation (OR, 5.05; 95% CI, 1.23-20.8; P=.03), mechanical ventilation (OR, 2.56; 95% CI, 1.24-5.28; P=.01), fecal incontinence (OR, 5.78; 95% CI, 1.52-22.0; P=.01), and exposure in the prior 30 days to meropenem (OR, 3.55; 95% CI, 1.04-12.1; P=.04), vancomycin (OR, 2.94; 95% CI, 1.18-7.32; P=.02), and metronidazole (OR, 4.22; 95% CI, 1.28-14.0; P=.02). CONCLUSIONS Rates of colonization and infection with CRKP were high in the LTACH setting, with nearly half of K. pneumoniae cultures demonstrating carbapenem resistance. Further studies are needed on interventions to limit the emergence of CRKP in LTACHs, including targeted surveillance screening of high-risk patients and effective antibiotic stewardship measures. Infect. Control Hosp. Epidemiol. 2015;37(1):55-60.

Lemierre's syndrome due to Fusobacterium necrophorum.

We present a case of a patient with Lemierre's syndrome caused by Fusobacterium necrophorum who developed a right frontal lobe brain abscess. We summarise the epidemiology, microbiology, pathogenesis, clinical presentation, diagnosis, complications, therapy, and outcomes of Lemierre's syndrome. F necrophorum is most commonly associated with Lemierre's syndrome: a septic thrombophlebitis of the internal jugular vein. Patients usually present with an exudative tonsillitis, sore throat, dysphagia, and unilateral neck pain. Diagnosis of septic thrombophlebitis is best confirmed by obtaining a CT scan of the neck with contrast. Complications of the disease include bacteraemia with septic abscesses to the lungs, joints, liver, peritoneum, kidneys, and brain. Treatment should include a prolonged course of intravenous beta-lactam antibiotic plus metronidazole.

Diagnosis of latent tuberculosis infection among HIV discordant partners using interferon gamma release assays.

BACKGROUND: There is limited data on the effect of HIV status and CD4 counts on performance of Interferon-g Release assays (IGRAs) for diagnosis of latent tuberculosis infection (LTBI). METHODS: A cross sectional study was conducted to assess the prevalence of and risk factors for a positive diagnostic test for LTBI, using tuberculin skin test (TST) and IGRAs among HIV-discordant couples in Zambia. RESULTS: A total of 596 subjects (298 couples) were enrolled. Median CD4 count among HIV positive persons was 388 cells/µl, (range 51-1330). HIV negative persons were more likely than their HIV positive partner, to have a positive diagnostic test for LTBI with TST (203 vs 128), QFT (171 vs 109) and TSPOT (156 vs. 109). On multivariate analysis, HIV negative status was an independent predictor for a positive QFT (OR = 2.22, 95% CI 1.42- 3.46) and TSPOT (OR = 1.79, 95% CI 1.16-2.77). Among HIV positive subjects a CD4 count ≥ 388 cells/µl was associated with a positive TST (OR = 1.76 95% CI 1.10-2.82) and QFT (OR = 1.71 95% CI 1.06-2.77) but not TSPOT (OR = 1.20 95% CI 0.74-1.94). CONCLUSIONS: Persons with HIV had significantly fewer positive diagnostic tests for LTBI with TST, QFT and TSPOT. Persons with a CD4 count < 388 cells/µl were less likely to have a positive TST or QFT, but not less likely to have a positive TSPOT. TSPOT may perform better than TST or QFT in HIV positive individuals.

Poor concordance between interferon-gamma release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals.

BACKGROUND: A new generation of diagnostic tests, the interferon-gamma release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their use in HIV-infected persons. METHODS: A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB [TSPOT] and QuantiFERON-TB Gold in Tube [QFT-3G]) compared to the tuberculin skin test (TST). RESULTS: 336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/microl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, [kappa = 0.16, 95% CI (-0.06, 0.39)], TST and QFT-3G [kappa = 0.23, 95% CI (-0.05, 0.51)], QFT-3G and TSPOT [kappa = 0.06, 95% CI (-0.1, 0.2)]. An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 < or = 200 cells/microl were significantly more likely to have an indeterminate result [OR = 3.6, 95% CI (1.9, 6.8)]. CONCLUSION: We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts < or = 200 cells/microl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.

Spectrum of CNS disease caused by rapidly growing mycobacteria.

We present a case of a patient with chronic meningoencephalitis caused by Mycobacterium abscessus. We also summarise the clinical features and outcomes of cases of CNS infection caused by rapidly growing mycobacteria that have been described in the literature. Rapidly growing mycobacteria are notorious for causing skin and soft-tissue infections after trauma or surgery, pulmonary disease in patients with cystic fibrosis, and disseminated disease in immunocompromised patients. CNS infection with this organism is extremely rare. Patients usually present with subacute to chronic meningitis, neutrophilic pleocytosis, and have a history of trauma or neurosurgery. The smears are often negative for acid-fast organisms, but may show Gram-positive rods. Treatment requires a long course of two or more antibiotics that have the ability to penetrate the blood-brain barrier, and possibly of steroids as immunomodulatory agents, such as those used in tuberculous meningitis.

Infections associated with haemophagocytic syndrome.

Haemophagocytic syndrome or haemophagocytic lymphohistiocytosis is a rare disease that is often fatal despite treatment. Haemophagocytic syndrome is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of lymphocytes or histiocytes with uncontrolled haemophagocytosis and cytokine overproduction. The syndrome is characterised by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinaemia. Haemophagocytic syndrome can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections. Infections associated with haemophagocytic syndrome are most frequently caused by viruses, particularly Epstein-Barr virus (EBV). We present a case of EBV-associated haemophagocytic syndrome in a young adult with no known immunosuppression. We briefly review haemophagocytic syndrome and then discuss its associated infections, particularly EBV and other herpes viruses, HIV, influenza, parvovirus, and hepatitis viruses, as well as bacterial, fungal, and parasitic organisms.

A painful thorn in the foot: a case of eumycetoma.

Madura foot or mycetoma is endemic in many developing countries. It is occasionally seen within the United States due to increasing international travel but it may sometimes be acquired within US soil. Herein, we present a case of a patient with a diagnosis of mycetoma acquired through trauma to the foot. In addition, we discuss the epidemiology, etiological agents, clinical presentation, diagnosis, and treatment of mycetomas. Clinicians need to recognize mycetoma early and institute treatment promptly to reduce the substantial morbidity associated with this devastating infection.

Hepatitis B reverse seroconversion in HIV-positive patients: case series and review of the literature.

Hepatitis B (HBV) reverse seroconversion is rare in HIV disease but can be fatal. We present a case series of 6 patients with reverse seroconversion and review 18 additional cases described in the literature. Elevated transaminases were seen in 13/21 (62%). Reverse seroconversion occurred more frequently in the setting of HIV virologic failure. Only 3 patients demonstrated reverse seroconversion in the setting of lamivudine or tenofovir withdrawal. 2/24 (8%) patients died from their HBV flare.

Autonomic nervous system dysfunction predicts poor prognosis in patients with mild to moderate tetanus.

BACKGROUND: Autonomic nervous system (ANS) dysfunction is present in up to one third of patients with tetanus. The prognostic value of ANS dysfunction is known in severe tetanus but its value is not well established in mild to moderate tetanus. METHODS: Medical records of all patients admitted with tetanus at two academic tertiary care centers in Karachi, Pakistan were reviewed. The demographic, clinical and laboratory data was recorded and analyzed. ANS dysfunction was defined as presence of labile or persistent hypertension or hypotension and sinus tachycardia, tachyarrythmia or bradycardia on EKG. Patients were divided into two groups based on presence of ANS dysfunction (ANS group and non ANS group). Tetanus severity was classified on the basis of Ablett criteria. RESULTS: Ninety six (64 males; 32 females) patients were admitted with the diagnosis over a period of 10 years. ANS group had 31 (32%) patients while non ANS group comprised of 65 (68%) patients. Both groups matched for age, gender, symptom severity, use of tetanus immunoglobulin and antibiotics. Twelve patients in ANS group had mild to moderate tetanus (Ablett I and II) and 19 patients had severe/very severe tetanus (Ablett III and IV). Fifteen (50%) patients in ANS group required ventilation as compared to 28 (45%) in non-ANS group (p = 0.09). Fourteen (47%) patients died in ANS group as compared to 10 (15%) in non ANS group (p= 0.002). Out of those 14 patients died in ANS group, six patients had mild to moderate tetanus and eight patients had severe/very severe tetanus. Major cause of death was cardiac arrhythmias (13/14; 93%) in ANS group and respiratory arrest (7/10; 70%) in non ANS group. Ten (33%) patients had complete recovery in ANS group while in non ANS group 35(48%) patients had complete recovery (p= 0.05). CONCLUSIONS: ANS dysfunction was present in one third of our tetanus population. 40% patients with ANS dysfunction had only mild to moderate tetanus. ANS dysfunction, irrespective of the need of mechanical ventilation or severity of tetanus, predicted poor outcome.