Comparative Bactericidal Activity Of Representative B-Lactams

B-Lactam sub-classes (penicillins, cephalosporins, monobactams and carbapenems) have different antibacterial effects against E. coli, K. pneumoniae, A. baumannii and P. aeruginosa.

source: J Antimicrob Chemother

Summary

Comparative Bactericidal Activity Of Representative ß-Lactams Against Enterobacterales, Acinetobacter Baumannii and Pseudomonas Aeruginosa

[Posted 25/May/2022]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: ß-Lactam sub-classes (penicillins, cephalosporins, monobactams and carbapenems) have different antibacterial effects against E. coli, K. pneumoniae, A. baumannii and P. aeruginosa. Extrapolation of in vitro pharmacodynamic findings from one species to another or one sub-class of ß-lactam to another is not justified.

BACKGROUND: There is surprisingly little comparative published data on the bactericidal action of different sub-classes of ß-lactams against aerobic Gram-negative rods, and the assumption is that all behave in the same way. Purpose of this study is to describe a systematic investigation of a representative penicillin, cephalosporin, monobactam and carbapenem against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.

DETAILS: Concentration-time-kill curves (TKC) were determined for three strains each of E. coli, K. pneumoniae, A. baumannii and P. aeruginosa. All strains were susceptible to the agents used. The antibiotics were piperacillin/tazobactam, ceftazidime, aztreonam and meropenem. The initial inoculum was 106 cfu/mL and TKC were determined over 48 h. The area-under-the-bacterial-kill curve to 24 h (AUBKC 24 log cfu.h/mL) and 48 h (AUBKC 48) were used to measure antibacterial effect (ABE). Population profiles before and after antibiotic exposure were recorded. Against E. coli and K. pneumoniae meropenem had a maximal ABE at >=MIC x 1 concentrations while piperacillin/tazobactam and ceftazidime had maximal effect at >=MIC x 4 and aztreonam at >=MIC x 8 concentrations. Ceftazidime, aztreonam and meropenem had less ABE against K. pneumoniae than E. coli. Against P. aeruginosa, meropenem was most bactericidal, with a maximum ABE at 8x/16 x MIC. Other ß-lactams had notably less ABE. In contrast, against A. baumannii, ceftazidime and meropenem had the greatest ABE, with a maximal effect at >=MIC x 4, concentration changes in population profiles were least apparent with E. coli.

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Source: Noel, A. R., Attwood, M., Bowker, K. E., et al. (2022). Comparative Bactericidal Activity Of Representative ß-Lactams Against Enterobacterales, Acinetobacter Baumannii and Pseudomonas Aeruginosa. Journal of Antimicrobial Chemotherapy. 2022; 77(5): 1306-1312. Published: May, 2022. DOI: 10.1093/jac/dkac026.



Hepatitis B Surface Antigen Levels

Hepatitis B virus genotype-specific HBsAg cutoffs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C, and D and can be an adjunct to FIB-4 to reduce the need for further testing.

source: J Infect Disease

Summary

Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study

[Posted 14/Jun/2022]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Hepatitis B virus genotype-specific HBsAg cutoffs may have utility in ruling out presence of cirrhosis in HBeAg-positive patients with genotypes B, C, and D and can be an adjunct to FIB-4 to reduce the need for further testing.

BACKGROUND: Serum hepatitis B surface antigen (HBsAg) levels correlate with the duration of chronic hepatitis B virus (HBV) infection and may predict the extent of hepatic fibrosis.

DETAILS: Analyzed data from the SONIC-B database, which contains data from 8 global randomized trials and 2 large hepatology centers. Relationship between HBsAg levels and presence of significant fibrosis (Ishak 3-4) or cirrhosis (Ishak 5-6) were explored, and clinically relevant cutoffs were identified to rule out cirrhosis. The dataset included 2779 patients: 1866 hepatitis B e antigen (HBeAg)-positive; 322 with cirrhosis. Among HBeAg-positive patients, lower HBsAg levels were associated with higher rates of significant fibrosis (odds ratio [OR], 0.419; P < .001) and cirrhosis (OR, 0.435; P < .001). No relationship was observed among HBeAg-negative patients. Among HBeAg-positive patients, genotype-specific HBsAg cutoffs had excellent negative predictive values (>97%) and low misclassification rates (<=7.1%) and may therefore have utility in ruling out cirrhosis. Diagnostic performance of the HBsAg cutoffs was comparable among patients in whom cirrhosis could not be ruled out with fibrosis 4 (FIB-4).

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Copyright © Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Source: Sonneveld, M. J., Hansen, B. H., Brouwer, W. P., et al. (2022). Hepatitis B Surface Antigen Levels Can Be Used to Rule Out Cirrhosis in Hepatitis B e Antigen-Positive Chronic Hepatitis B: Results From the SONIC-B Study. J Infect Disease. 2022; 225(11): 1967-1973. Published: June 6, 2022. DOI: 10.1093/infdis/jiaa192.



Development and Validation of Bloomy Prediction Scores

The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections.

source: The Lancet

Summary

Development and Validation of Bloomy Prediction Scores For 14-Day and 6-Month Mortality In Hospitalised Adults With Bloodstream Infections

A Multicentre, Prospective, Cohort Study.

[Posted 20/Apr/2022]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections.

BACKGROUND: The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. Study aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections.

DETAILS: The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factors and Clinical Outcomes (BLOOMY) study is a prospective, multicentre cohort study at six German tertiary care university hospitals to develop and validate two scores assessing 14-day and 6-month mortality in patients with bloodstream infections. We excluded patients younger than 18 years or who were admitted to an ophthalmology or psychiatry ward. Microbiological, clinical, laboratory, treatment, and survival data were prospectively collected on day 0 and day 3 and then from day 7 onwards, weekly. Participants were followed up for 6 months. All patients in the derivation cohort who were alive on day 3 were included in the analysis. Predictive scores were developed using logistic regression and Cox proportional hazards models with a machine-learning approach. Validation was completed using the C statistic and predictive accuracy was assessed using sensitivity, specificity, and predictive values. Between Feb 1, 2017, and Jan 31, 2019, 2568 (61.5%) of 4179 eligible patients were recruited into the derivation cohort. The in-hospital mortality rate was 23.75% (95% CI 22.15-25.44; 610 of 2568 patients) and the 6-month mortality rate was 41.55% (39.54-43.59; 949 of 2284). The model predictors for 14-day mortality (C statistic 0.873, 95% CI 0.849-0.896) and 6-month mortality (0.807, 0.784-0.831) included age, body-mass index, platelet and leukocyte counts, C-reactive protein concentrations, malignancy (ie, comorbidity), in-hospital acquisition, and pathogen. Additional predictors were, for 14-day mortality, mental status, hypotension, and the need for mechanical ventilation on day 3 and, for 6-month mortality, focus of infection, in-hospital complications, and glomerular filtration rate at the end of treatment. The scores were validated in a cohort of 1023 patients with bloodstream infections, recruited between Oct 9, 2019, and Dec 31, 2020. The BLOOMY 14-day score showed a sensitivity of 61.32% (95% CI 51.81-70.04), a specificity of 86.36% (83.80-88.58), a positive predictive value (PPV) of 37.57% (30.70-44.99), and a negative predictive value (NPV) of 94.35% (92.42-95.80). The BLOOMY 6-month score showed a sensitivity of 69.93% (61.97-76.84), a specificity of 66.44% (61.86-70.73), a PPV of 40.82% (34.85-47.07), and a NPV of 86.97% (82.91-90.18).

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Source: Tacconelli, E., Gopel, S., Gladstone, B. P., et al. (2022). Development and Validation of Bloomy Prediction Scores For 14-Day and 6-Month Mortality In Hospitalised Adults With Bloodstream Infections: A Multicentre, Prospective, Cohort Study. The Lancet. 2022; 22(5): 731-741.Published: May 1, 2022. DOI: 10.1016/S1473-3099(21)00587-9.



A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine

RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults.

source: J Infect Disease

Summary

[Posted 27/Apr/2022]

AUDIENCE: Infectious Disease, Family Medicine, Ob/Gyn

KEY FINDINGS: RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization.

BACKGROUND: Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B.

DETAILS: Adults 18-49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated. RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6-16.9 for RSV A and 10.3-19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9-5.2 and 3.7-5.1, respectively, at 12 months postvaccination.

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Source: Walsh, E. E., Falsey, A. R., Scott, D. A., et al. (2022). A Randomized Phase 1/2 Study of a Respiratory Syncytial Virus Prefusion F Vaccine. J Infect Disease. 2022; 225(8): 1357-1366. Published: April 15, 2022. DOI: 10.1093/infdis/jiab612.



Influence of Placental and Peripheral Malaria Exposure In Fetal Life

The subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.

source: BMJ DRC

Summary

Influence of Placental and Peripheral Malaria Exposure In Fetal Life On Cardiometabolic Traits In Adult Offspring

[Posted 12/Apr/2022]

AUDIENCE: Endocrinology, Pediatric, Ob/Gyn

KEY FINDINGS: Using the state-of-the-art euglycemic clamp technique, we were unable to prove our a priori primary hypothesis of peripheral insulin resistance in young adult offspring of pregnancies affected by malaria. However, the subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.

BACKGROUND: Fetal malaria exposure may lead to intrauterine growth restriction and increase the risk of developing diabetes and cardiovascular diseases in adulthood. We investigated the extent to which fetal peripheral and placental malaria exposure impacts insulin sensitivity and secretion, body composition and cardiometabolic health 20 years after in utero malaria exposure.

DETAILS: During the study, traced 101 men and women in Muheza district, Tanga region whose mothers participated in a malaria chemosuppression during a pregnancy study in 1989-1992. All potential participants were screened for malaria, hepatitis B and HIV to ascertain study eligibility. Seventy-six individuals (44 men, 32 women) were included in this cohort study. The participants underwent a thorough clinical examination including anthropometric measurements, ultrasound scanning for abdominal fat distribution, blood pressure, 75 g oral glucose tolerance test, an intravenous glucose tolerance test followed by a hyperinsulinemic euglycemic clamp and a submaximal exercise test. Offspring exposed to placental malaria during pregnancy had significantly higher 30-minute plasma post-glucose load levels, but no significant difference in peripheral insulin resistance, insulin secretion or other cardiometabolic traits compared with non-exposed individuals.

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Source: Grunnet, L. G., Bygbjerg, I. C., Mutabingwa, T. K., et al. (2022). Influence of Placental and Peripheral Malaria Exposure In Fetal Life On Cardiometabolic Traits In Adult Offspring. BMJ Open Diabetes Research and Care. 2022; 10(2): e002639. Published: April 4, 2022. DOI: 10.1136/bmjdrc-2021-002639.



The Use of Monoclonal Antibody Therapy in Pediatric Patients with COVID-19

The administration of MCA therapy in high-risk pediatric patients in the pediatric ED was well-tolerated with subjective improvement noted in COVID-19 symptoms post-therapy.

source: Int J Emerg Med

Summary

A Retrospective Case Series.

[Posted 11/Apr/2022]

AUDIENCE: Emergency Medicine, Pediatric, Infectious Disease

KEY FINDINGS: The administration of MCA therapy in high-risk pediatric patients in the pediatric ED was well-tolerated with subjective improvement noted in COVID-19 symptoms post-therapy. Further studies are necessary to determine the role MCA therapy may play in reducing morbidity from COVID-19 infection in high-risk pediatric patients.

BACKGROUND: Monoclonal antibody (MCA) therapies have been utilized under emergency use authorization (EUA) for high-risk pediatric patients with mild to moderate coronavirus disease 2019 (COVID-19) in the outpatient setting since late 2019. The purpose of this study was to describe the use of MCA therapy in pediatric patients in the pediatric emergency department (ED) at a large community hospital.

DETAILS: This was a retrospective case series of high-risk pediatric patients 12 to 17 years of age who received MCA therapy in the pediatric ED between December 8, 2020 and June 3, 2021. The primary outcome was to describe the patient characteristics, clinical presentation, and safety profile of the pediatric population that received MCA therapy. The secondary outcome was to describe the incidence of hospitalizations or ED visits up to 28 days following therapy. A total of 44 patients were included in the analysis. The median number of days of symptoms was 4 with 41% of patients having symptoms between 0 and 3 days at time of MCA administration. Only one patient experienced a mild adverse event that did not require epinephrine administration. Two patients returned to the ED for reevaluation during the study follow-up period. No patients required admission within 28 days post-therapy.

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Source: Santos, J.D.L., Bhisitkul, D., Carman, M., et al. (2022). The Use of Monoclonal Antibody Therapy in Pediatric Patients with COVID-19: A Retrospective Case Series. Int J Emerg Med. 2022; 15(9). Published: March 3, 2022. DOI: 10.1186/s12245-022-00414-8.



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