scholarly journals 1132. Evaluating an Amoxicillin Dosing Regimen for Community Acquired Pneumonia: A Quality Improvement Initiative Using Clinical and Laboratory Data

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S657-S657
Author(s):  
Emma Keeler ◽  
Jonathan Beus ◽  
Molly Hayes ◽  
Joseph Zorc ◽  
Talene Metjian ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Treatment Failure ◽  
Laboratory Data ◽  
Community Acquired Pneumonia ◽  
Quality Improvement Initiative ◽  
Diagnosis Code ◽  
Dosing Regimen ◽  
Dosing Strategy ◽  
Family Preference

Abstract Background Amoxicillin 90 mg/kg/day divided twice daily is recommended for children with mild community acquired pneumonia (CAP). While adequate for fully susceptible Streptococcus pneumoniae isolates, three times daily dosing allows achievement of greater amoxicillin exposure, which may be necessary for isolates with penicillin minimum inhibitory concentrations (MIC) of ≥ 2 μg/mL. We evaluated our current twice daily amoxicillin dosing strategy by characterizing 1) the MIC distribution among S. pneumoniae isolates and 2) the frequency of clinical amoxicillin treatment failures. Methods We performed a retrospective cohort study of all S. pneumoniae isolates from sterile and non-sterile sites between 2017-2020. Breakpoints established by the CLSI were used for both meningitis and non-meningitis isolates. Only the first isolate per patient was included. We also evaluated the frequency of amoxicillin treatment failure in patients diagnosed with CAP who were discharged from the ED in 2019. CAP was defined as a discharge diagnosis code for pneumonia and an antibiotic prescription. Treatment failure was defined as an ED or primary care revisit, or admission, within 14 days during which an antibiotic change was made. Results 28 S. pneumoniae isolates were identified from sterile sites between 2017-2020 and 171 isolates were identified overall. All isolates from sterile sites had penicillin MICs of ≤ 2 μg/mL and 165 (96%) of isolates overall had penicillin MICs of ≤ 2 μg/mL (Table 1). Of these, 10 isolates had MICs of 2 μg/mL, all from non-sterile sites. In 2019, 589 patients were treated for CAP in the ED; 447 (76%) received amoxicillin and 142 (24%) were treated with alternative antibiotics. Treatment failures occurred in 15 amoxicillin-treated patients (3.3%, 95% confidence interval 1.9-5.5%) and in 5 patients (3.5%, 95% confidence interval 1.2-8.0%) treated with alternative antibiotics. Conclusion In vitro penicillin resistance was rare at our institution. Further, given that S. pneumoniae is rarely identified by culture, we also demonstrated that clinical amoxicillin treatment failures were infrequent using twice daily amoxicillin dosing. Coupled with provider and family preference, these data supported continuing our current practice of twice daily amoxicillin dosing. Disclosures All Authors: No reported disclosures

scholarly journals Comparison of Once-Daily versus Twice-Daily Administration of Cefdinir against Typical Bacterial Respiratory Tract Pathogens

2001 ◽  
Vol 45 (10) ◽  
pp. 2936-2938 ◽  
Author(s):  
Gigi H. Ross ◽  
Laurie Baeker Hovde ◽  
Khalid H. Ibrahim ◽  
Yasir H. Ibrahim ◽  
John C. Rotschafer
Keyword(s):  
Respiratory Tract ◽  
Community Acquired Pneumonia ◽  
Pharmacodynamic Model ◽  
Daily Administration ◽  
Respiratory Pathogens ◽  
Daily Regimen ◽  
Dosing Regimen ◽  
Once Daily ◽  
Dosing Strategy

ABSTRACT In an in vitro pharmacodynamic model, a twice-daily cefdinir dosing regimen was more effective than a once-daily regimen against common bacterial respiratory pathogens in producing 3-log10killing and preventing the occurrence of regrowth at 24 h. Twice-daily administration is likely the more appropriate cefdinir dosing strategy for the treatment of community-acquired pneumonia.

scholarly journals Resistance against macrocyclic lactones in Psoroptes ovis in cattle

2019 ◽  
Author(s):  
Wouter van Mol ◽  
Nathalie De Wilde ◽  
Stijn Casaert ◽  
Zhenzhen Chen ◽  
Marieke Vanhecke ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Treatment Failure ◽  
Lower Limit ◽  
Macrocyclic Lactone ◽  
Macrocyclic Lactones ◽  
Psoroptes Ovis ◽  
Knock Down ◽  
Clinical Index

Abstract Background Psoroptic mange is an important disease in beef cattle, and Belgian Blue cattle are particularly susceptible. Treatment failure of macrocyclic lactones against Psoroptes ovis has been reported, but clear evidence of in vivo resistance is still lacking. This study was conducted to investigate ML efficacy in 16 beef farms in Belgium and The Netherlands in vivo and in vitro.Methods On each farm a group of animals (n= 7-14) with clinical psoroptic mange was treated with two subcutaneous injections of a macrocyclic lactone with 7-10 days interval (15 farms) or a single injection with a long-acting macrocyclic lactone (1 farm). In vivo efficacy was assessed by the reduction in mite counts and clinical index (part of the body affected by lesions), the cure rate after the first treatment round and the number of treatment rounds needed to cure all animals. In vitro knock-down and mortality was evaluated in a contact test.Results Cure rates after the first treatment round varied from 0-80%. All farms needed two or more rounds of treatments to obtain full efficacy. Clinical index had a high variation and only started to reduce after the second treatment round. Only three farms were categorized as susceptible with a mean mite count reduction>95% and a lower limit of the uncertainty interval>90%. One farm had a mean reduction>95%, but its lower limit of the confidence interval was <90%. All other farms had mean reductions<95% and lower limits of their uncertainty intervals<90%. No correlation was found between in vitro lethal dose 50 and knock-down dose 50 values and any parameter of in vivo efficacy.Conclusion Unambiguous treatment failure was detected on 12/16 beef farms, confirming the presence of macrocyclic lactone resistance in Belgian Blue beef farms. In vitro parameters could not discriminate the farms based on their in vivo susceptibility. The mean reduction in mite counts and the lower limit of the confidence interval stood out as most useful parameter to identify acaricide resistance.

Red Grape Polyphenol Oral Administration improves Immune Response in Women Affected by Nickel-Mediated Allergic Contact Dermatitis

2020 ◽  
Vol 20 ◽  
Author(s):  
Thea Magrone ◽  
Emilio Jirillo ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Paolo Romita ◽  
...  
Keyword(s):  
Contact Dermatitis ◽  
Oral Administration ◽  
Allergic Contact Dermatitis ◽  
Laboratory Data ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Red Grape ◽  
Allergic Contact ◽  
Drop Outs

Background: Our previous findings demonstrated that in vitro supplementation of polyphenols, extracted from seeds of red grape (Nero di Troia cultivar), to peripheral lymphomonocytes from patients affected by allergic contact dermatitis (ACD) to nickel (Ni) could reduce release of pro-inflammatory cytokines and nitric oxide (NO), while increasing levels of interleukin (IL)-10, an anti-inflammatory cytokine. Objective: To assess whether an intervention with oral administration of polyphenols leads to a reduction of peripheral biomarkers in ACD patients. Method: At T0, 25 patients affected by ACD to Ni were orally administered with 300 mg polyphenols prodie extracted from seeds of red grape (Nero di Troia cultivar) (NATUR-OX®) for 3 months (T1). Other 25 patients affected by ACD to Ni received placebo only for the same period of time. Serum biomarkers were analyzed at T0 and T1. In both groups seven drop outs were recorded. Result: At T1 in comparison to T0, in treated patients, values of IFN-γ, IL-4, IL-17, PTX3 and NO decreased, while IL-10 levels increased when compared with T0 values. Conversely, in placebo-treated patients no modifications of biomarkers were evaluated at T1. Conclusion: Present laboratory data rely on the anti-oxidant, anti-inflammatory and anti-allergic properties of polyphenols.

scholarly journals Effect of Splinting in Accuracy of Two Implant Impression Techniques

2014 ◽  
Vol 40 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Erica Dorigatti de Avila ◽  
Fernanda de Matos Moraes ◽  
Sabrina Maria Castanharo ◽  
Marcelo Antonialli Del'Acqua ◽  
Francisco de Assis Mollo
Keyword(s):  
Confidence Interval ◽  
Analysis Of Variance ◽  
Impression Material ◽  
Titanium Screw ◽  
Standard Preparation ◽  
Implant Abutment ◽  
Interface Gaps ◽  
Group 2 ◽  
Group 1

Because there is no consensus in the literature about the need for a splint between copings, the aim of this study was to evaluate, in vitro, the accuracy of 2 impression techniques for implant-supported prostheses. A master cast was fabricated with four parallel implant abutment analogs and a passive framework. Two groups with 5 casts each were formed: Group 1 (squared impression copings with no splint: S) and Group 2 (splinted squared impression copings, using metal drill burs and Pattern resin: SS). The impression material used was polyvinyl siloxane with open trays for standard preparation of the casts. For each cast, the framework was positioned, and a titanium screw was tightened with 10 N·cm torque in analog A, after which measurements of the abutment-framework interface gaps were performed at analogs C and D. This process was repeated for analog D. These measurements were analyzed using software. A one-way analysis of variance (ANOVA) with a confidence interval of 95% was used to analyze the data. Significant differences were detected between S and SS in relation to the master cast (P ≤ 0.05). The median values of the abutment-framework interface gaps were as follows: master cast: 39.64 μm; squared impression copings with no splint: 205.86 μm; splinted squared impression copings: 99.19 μm. Under the limitations of this study, the technique presented for Group 2 produces better results compared with the technique used for Group 1.

Resistance-guided treatment of Mycoplasma genitalium infection at a UK sexual health centre

2021 ◽  
pp. 095646242098776
Author(s):  
Ruairi JH Conway ◽  
Seamus Cook ◽  
Cassandra Malone ◽  
Simon Bone ◽  
Mohammed Osman Hassan-Ibrahim ◽  
...  
Keyword(s):  
Single Dose ◽  
Confidence Interval ◽  
Sexual Health ◽  
Treatment Failure ◽  
Inflammatory Disease ◽  
Health Centre ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
Fluoroquinolone Resistance ◽  
Treatment Failure Rate

We evaluated the ResistancePlus® MG assay in providing macrolide resistance-guided treatment (RGT) for Mycoplasma genitalium infection at a UK sexual health centre. M. genitalium–positive samples from men with urethritis and women with pelvic inflammatory disease (PID) were tested for macrolide resistance–mediating mutations (MRMMs). MRMM-positive infections were given moxifloxacin 400 mg; otherwise 2 g azithromycin (1 g single dose and then 500 mg OD) was given. Among 57  M. genitalium–positive patients (32 men and 25 women), MRMMs were detected in 41/57 (72% [95% confidence interval (95% CI) 58–83%). Thirty-two of 43 patients given RGT attended for test of cure. Treatment failure rate was significantly lower at 1/32 (3%) than 10/37 (27%) before RGT ( n = 37 [men = 23 and women = 17]; p = 0.008). Treatment failure was lower in male urethritis (0/15 vs. 7/21 p = 0.027) but not in female PID. There was a trend of a shorter time to negative test of cure (TOC) in male urethritis (55.1 [95% 43.7–66.4] vs. 85.1 [95% CI CI 64.1–106.0] days, p = 0.077) but not in female PID. Macrolide resistance is higher than previous UK reports and higher than expected. RGT reduces overall treatment failure and is particularly beneficial in M. genitalium urethritis. Fluoroquinolone resistance will continue to rise with increasing fluoroquinolone use, and RGT is critical to direct appropriate azithromycin use and prevent overuse of moxifloxacin.

scholarly journals 10. Kinetics of Post-Vaccination Seroprotection to S. Pneumonia for the Immune-Compromised and Vaccine-Naïve Populations

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Jeffrey Gruenglas ◽  
James Mond ◽  
Micaela Scobie ◽  
Cynthia Tolman ◽  
Joseph Martinez
Keyword(s):  
Capsular Polysaccharide ◽  
The Elderly ◽  
Community Acquired Pneumonia ◽  
Prior History ◽  
Antibody Activity ◽  
Vaccine Response ◽  
Serum Samples ◽  
Opsonic Activity ◽  
And Control

Abstract Background S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization. Methods Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine. Results There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2. Conclusion Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies. Disclosures All Authors: No reported disclosures

scholarly journals A Prospective Open-Label Multicentre Trial on the Use of 1 G, Once Daily Ceftriaxone in Lower Respiratory Tract Infections

1994 ◽  
Vol 5 (suppl c) ◽  
pp. 3C-8C ◽  
Author(s):  
Donald E Low ◽  
Lionel A Mandell
Keyword(s):  
Respiratory Tract ◽  
Treatment Failure ◽  
Lower Respiratory Tract ◽  
Study Drug ◽  
Open Label ◽  
In Vitro Susceptibility ◽  
Once Daily ◽  
Minimal Inhibitory Concentrations ◽  
Tract Infections

This prospective. single open-label sludy was conducted in 14 Canadian centres to assess lhe efncacy of I g, once a day intravenous ceftriaxone treatment administered for a minimum of three days in patients with lower respiratory tract infection. There were 137 patients enrolled. Age varied between 19 and 95 years (mean 68 years). Mosl patients (91 %) were diagnosed with community acquired pneumonia without bacteremia. Most of the cases (82%) were defined as modcralc or severe. Patients received ceftriaxone treatment for an average or five days. Macrolidcs or metronidazole were administered concomitantly wilh ceftriaxone in 34 patienls (25%). After a minimum of three days of ceftriaxone treatment. 59 palicnls (43%) were switched to oral antibiotics. Favourable treatment outcome was found in 92.9% and treatment failure (including relapse of infection) in 7.1 % o lpalicnls. Evaluable patients accounted for 91 % of patients enrolled in the study. Clinical cure and clinical improvement were achieved in 64.6 and 28.3% of the evaluable patients. respectively. Relapse of infection occurred in two patients (1.8%). and treatment failure was recorded in six cases (5.3%). Twelve patients (8.8%) died clue to reasons unrelated to the sludy treatment. Three adverse event (hives, diarrhea and phlebitis at the injection site) were possibly related to the study drug. A cross-Canada in vitro susceptibility surveillance study of bacterial pathogens. frequently the cause of pneumonia. found ceftriaxone to have minimal inhibitory concentrations in 90% of isolates that would support such a dosing regimen. with the exception of Enterobacter species. These rcsults support the use of 1 g, once daily ceftriaxone for the empirical treatment of pneumonia in those patients requiring hospitalization.

scholarly journals Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2607
Author(s):  
Yuzhen Gao ◽  
Jingjing Cao ◽  
Pan Xing ◽  
Ralf Altmeyer ◽  
Youming Zhang
Keyword(s):  
Respiratory Syncytial Virus ◽  
Confidence Interval ◽  
The Elderly ◽  
Term Treatment ◽  
Fusion Inhibitors ◽  
Long Term Treatment ◽  
Statistical Program ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a major pathogen that causes severe lower respiratory tract infection in infants, the elderly and the immunocompromised worldwide. At present no approved specific drugs or vaccines are available to treat this pathogen. Recently, several promising candidates targeting RSV entry and multiplication steps are under investigation. However, it is possible to lead to drug resistance under the long-term treatment. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). The statistical program MacSynergy II was employed to determine synergism, additivity or antagonism between drugs. From the result, we found that combinations of ALS8176 and Ziresovir or GS5806 exhibit additive effects against RSV in vitro, with interaction volume of 50 µM2% and 31 µM2% at 95% confidence interval, respectively. On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from −50 µM2 % to −176 µM2 % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations.

scholarly journals In Vitro Infection Model Characterizing the Effect of Efflux Pump Inhibition on Prevention of Resistance to Levofloxacin and Ciprofloxacin in Streptococcus pneumoniae

2007 ◽  
Vol 51 (11) ◽  
pp. 3988-4000 ◽  
Author(s):  
Arnold Louie ◽  
David L. Brown ◽  
Weiguo Liu ◽  
Robert W. Kulawy ◽  
Mark R. Deziel ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Efflux Pump ◽  
Community Acquired Pneumonia ◽  
Fluoroquinolone Resistance ◽  
Infection Model ◽  
Wild Type ◽  
Efflux Pump Inhibition ◽  
Short Term Exposure ◽  
Emergence Of Resistance

ABSTRACT The prevalence of fluoroquinolone-resistant Streptococcus pneumoniae is slowly rising as a consequence of the increased use of fluoroquinolone antibiotics to treat community-acquired pneumonia. We tested the hypothesis that increased efflux pump (EP) expression by S. pneumoniae may facilitate the emergence of fluoroquinolone resistance. By using an in vitro pharmacodynamic infection system, a wild-type S. pneumoniae strain (Spn-058) and an isogenic strain with EP overexpression (Spn-RC2) were treated for 10 days with ciprofloxacin or levofloxacin in the presence or absence of the EP inhibitor reserpine to evaluate the effect of EP inhibition on the emergence of resistance. Cultures of Spn-058 and Spn-RC2 were exposed to concentration-time profiles simulating those in humans treated with a regimen of ciprofloxacin at 750 mg orally once every 12 h and with regimens of levofloxacin at 500 and 750 mg orally once daily (QD; with or without continuous infusions of 20 μg of reserpine/ml). The MICs of ciprofloxacin and levofloxacin for Spn-058 were both 1 μg/ml when susceptibility testing was conducted with each antibiotic alone and with each antibiotic in the presence of reserpine. For Spn-RC2, the MIC of levofloxacin alone and with reserpine was also 1 μg/ml; the MICs of ciprofloxacin were 2 and 1 μg/ml, respectively, when determined with ciprofloxacin alone and in combination with reserpine. Reserpine, alone, had no effect on the growth of Spn-058 and Spn-RC2. For Spn-058, simulated regimens of ciprofloxacin at 750 mg every 12 h or levofloxacin at 500 mg QD were associated with the emergence of fluoroquinolone resistance. However, the use of ciprofloxacin at 750 mg every 12 h and levofloxacin at 500 mg QD in combination with reserpine rapidly killed Spn-058 and prevented the emergence of resistance. For Spn-RC2, levofloxacin at 500 mg QD was associated with the emergence of resistance, but again, the resistance was prevented when this levofloxacin regimen was combined with reserpine. Ciprofloxacin at 750 mg every 12 h also rapidly selected for ciprofloxacin-resistant mutants of Spn-RC2. However, the addition of reserpine to ciprofloxacin therapy only delayed the emergence of resistance. Levofloxacin at 750 mg QD, with and without reserpine, effectively eradicated Spn-058 and Spn-RC2 without selecting for fluoroquinolone resistance. Ethidium bromide uptake and efflux studies demonstrated that, at the baseline, Spn-RC2 had greater EP expression than Spn-058. These studies also showed that ciprofloxacin was a better inducer of EP expression than levofloxacin in both Spn-058 and Spn-RC2. However, in these isolates, the increase in EP expression by short-term exposure to ciprofloxacin and levofloxacin was transient. Mutants of Spn-058 and Spn-RC2 that emerged under suboptimal antibiotic regimens had a stable increase in EP expression. Levofloxacin at 500 mg QD in combination with reserpine, an EP inhibitor, or at 750 mg QD alone killed wild-type S. pneumoniae and strains that overexpressed reserpine-inhibitable EPs and was highly effective in preventing the emergence of fluoroquinolone resistance in S. pneumoniae during therapy. Ciprofloxacin at 750 mg every 12 h, as monotherapy, was ineffective for the treatment of Spn-058 and Spn-RC2. Ciprofloxacin in combination with reserpine prevented the emergence of resistance in Spn-058 but not in Spn-RC2, the EP-overexpressing strain.

Sign in / Sign up

Export Citation Format

Share Document