In 2009, a lethal case of Crimean-Congo hemorrhagic fever (CCHF), acquired by a US soldier in Afghanistan, was treated at a medical center in Germany and resulted in nosocomial transmission to 2 ...health care providers (HCPs). After his arrival at the medical center (day 6 of illness) by aeromedical evacuation, the patient required repetitive bronchoscopies to control severe pulmonary hemorrhage and renal and hepatic dialysis for hepatorenal failure. After showing clinical improvement, the patient died suddenly on day 11 of illness from cerebellar tonsil herniation caused by cerebral/cerebellar edema. The 2 infected HCPs were among 16 HCPs who received ribavirin postexposure prophylaxis. The infected HCPs had mild or no CCHF symptoms. Transmission may have occurred during bag-valve-mask ventilation, breaches in personal protective equipment during resuscitations, or bronchoscopies generating infectious aerosols. This case highlights the critical care and infection control challenges presented by severe CCHF cases, including the need for experience with ribavirin treatment and postexposure prophylaxis.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) ...assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults.
This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter Reed Army Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18–50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT02670187) and is completed.
Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five 20% with 0·67 mg, 11 44% with 2 mg, and seven 28% with 6 mg), and malaise or fatigue (five 20% with 0·67 mg, seven 28% with 2 mg, and two 8% with 6 mg). The most common local solicited symptoms were administration site pain (23 92% with all three doses) and tenderness (21 84% with all three doses). Most solicited symptoms were reported as mild (19 76% with 0·67 mg, 20 80% with 2 mg, and 17 68% with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg group, three in the 2 mg group, and seven in the 6 mg group). Of these 15 increases, five (33%) were deemed possibly related to study treatment (one in the 2 mg group and four in the 6 mg group). Seroconversion measured by S1-ELISA occurred in 59 (86%) of 69 participants and 61 (94%) of 65 participants after two and three vaccinations, respectively. Neutralising antibodies were detected in 34 (50%) of 68 participants. T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. There were no differences in immune responses between dose groups after 6 weeks. At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively.
The GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus.
US Department of the Army and GeneOne Life Science.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal ...penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection.
Objective:
We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB.
Methods:
This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation.
Results:
Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively.
Conclusions and Relevance:
D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The most recent Zaire Ebolavirus (ZEBOV) outbreak was the largest and most widespread in recorded history, emphasizing the need for an effective vaccine. Here, we analyzed human cellular immune ...responses induced by a single dose of the rVSV-ZEBOV vaccine candidate, which showed significant protective efficacy in endemic populations in Guinea. This is the first in-depth characterization of ZEBOV-GP specific, circulating follicular T cells (cTfh). Since antibody titers correlated with protection in preclinical models of ZEBOV infection, Tfh were predicted to correlate with protection. Indeed, the ZEBOV-specific cTfh data correlated with antibody titers in human vaccines and unexpectedly with the Tfh17 subset. The combination of two cutting edge technologies allowed the immuno-profiling of rare cell populations and may help elucidate correlates of protection for a variety of vaccines.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background. Three full doses of RTS,S/AS01 malaria vaccine provides partial protection against controlled human malaria parasite infection (CHMI) and natural exposure. Immunization regimens, ...including a delayed fractional third dose, were assessed for potential increased protection against malaria and immunologie responses. Methods. In a phase 2a, controlled, open-label, study of healthy malaria-naive adults, 16 subjects vaccinated with a 0-, 1-, and 2-month full-dose regimen (012M) and 30 subjects who received a 0-, 1-, and 7-month regimen, including a fractional third dose (FxO17M), underwent CHMI 3 weeks after the last dose. Plasmablast heavy and light chain immunoglobulin messenger RNA sequencing and antibody avidity were evaluated. Protection against repeat CHMI was evaluated after 8 months. Results. A total of 26 of 30 subjects in the FxO17M group (vaccine efficacy VE, 86.7% 95% confidence interval CI, 66.8%-94.6%; P<.0001) and 10 of 16 in the 012M group (VE, 62.5% 95% CI, 29.4%-80.1%; P=.0009) were protected against infection, and protection differed between schedules (P=.040, by the log rank test). The fractional dose boosting increased antibody somatic hypermutation and avidity and sustained high protection upon rechallenge. Discussions. A delayed third fractional vaccine dose improved immunogenicity and protection against infection. Optimization of the RTS,S/AS01 immunization regimen may lead to improved approaches against malaria. Clinical Trials Registration. NCT01857869.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Study Objective
The preferred antibiotic salvage regimen for persistent methicillin‐resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety ...of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post‐ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90‐day readmission for MRSAB, 90‐day all‐cause mortality, MRSAB‐related mortality, and incidence of antibiotic‐associated adverse effects.
Design
Single‐center, retrospective cohort study between January 1, 2016, and December 31, 2021.
Setting
State University of New York Upstate University Hospital, a 748‐bed tertiary care, academic medical center in Syracuse, NY.
Patients
Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti‐MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated.
Measurements and Main Results
Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin‐associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline‐associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post‐ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90‐day readmission for MRSAB. 90‐day all‐cause mortality and MRSAB‐related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively.
Conclusions
Vancomycin plus ceftaroline may represent an effective and well‐tolerated salvage regimen option for persistent MRSAB.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Staphylococcus aureus bacteremia (SAB) is a common infectious disease (ID).•Pharmacists are well-positioned to assist ID consultation (IDC) with SAB management.•We implemented a ...pharmacist-facilitated, SAB evidence-based bundle (EBB) initiative.•We observed improved adherence to the EBB and several clinical outcomes for SAB.•SAB management may be optimized with collaboration between pharmacists and IDC.
To evaluate a pharmacist-facilitated evidence-based bundle (EBB) initiative with infectious disease consultation (IDC) for Staphylococcus aureus bacteremia (SAB).
This was a before-and-after quasi-experimental study of adult patients with SAB before and after the pharmacist-facilitated EBB initiative, which included IDC, timely definitive antibiotics, source control, echocardiography, and repeat blood cultures.
Ninety and 111 patients were included in pre- and post-intervention cohorts, respectively. We observed significant increases in adherence to all 5 (4.4% vs 68.5%, P < 0.001) and 4 (10.0% vs 76.6%, P < 0.001) EBB elements. Time to definitive antibiotics (48 vs 16 hours, P < 0.001), time to IDC (43.5 vs 32 hours, P < 0.001), SAB duration (95 vs 66 hours, P = 0.009), persistent SAB (18.9% vs 9.0%, P = 0.041), and length of stay (14 vs 13 days, P = 0.027) also improved. No statistically significant differences for SAB-related readmission or all-cause mortality were observed.
Our pharmacist-facilitated SAB initiative was associated with improved EBB adherence and clinical outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). ...Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization;
infection (CDI) cases; and clinicians' perceptions of the AOS via a survey following the final study phase.
This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31.
The study was conducted in a 752-bed tertiary care, academic medical center.
Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults.
For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90;
< .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939;
= .001), fluoroquinolone orders (407 vs 175;
< .001), carbapenem orders (147 vs 106;
= .024), and clindamycin orders (113 vs 73;
= .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902;
= .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4;
= .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics.
Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.
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