scholarly journals β-Lactam and Fluoroquinolone Combination Antibiotic Therapy for Bacteremia Caused by Gram-Negative Bacilli

2009 ◽  
Vol 53 (4) ◽  
pp. 1386-1394 ◽  
Author(s):  
Majdi N. Al-Hasan ◽  
John W. Wilson ◽  
Brian D. Lahr ◽  
Kristine M. Thomsen ◽  
Jeanette E. Eckel-Passow ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Antibiotic Therapy ◽  
Cox Regression ◽  
Receive Combination Therapy ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Gram Negative ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
First Time

ABSTRACT The role of combination antibiotic therapy with a beta-lactam and a fluoroquinolone for bacteremia caused by gram-negative bacilli, to our knowledge, has not been previously described. Much of the previous study of combination therapy has included beta-lactams and aminoglycosides. We conducted a large retrospective cohort study to evaluate 28-day all-cause mortality in patients with monomicrobial bacteremia due to aerobic gram-negative bacilli who received either a combination of beta-lactams and fluoroquinolones or beta-lactam monotherapy. We enrolled adult patients admitted to Mayo Clinic hospitals from 1 January 2001 to 31 October 2006 in the study. After stratification of patients by Pitt bacteremia scores, we used Cox regression models to estimate the hazard ratios (HR) for 28-day all-cause mortality after adjusting for the propensity to receive combination therapy. We identified 398 and 304 unique patients with bacteremia caused by gram-negative bacilli who received single and combination antibiotic therapy, respectively. In less severely ill patients with Pitt bacteremia scores of <4, combination therapy was associated with lower 28-day mortality than single therapy (4.2% [9 of 214] versus 8.8% [28 of 319]; adjusted HR, 0.44; 95% confidence interval [CI], 0.20 to 0.98; P = 0.044). In critically ill patients with Pitt bacteremia scores of ≥4, there was no difference in 28-day mortality between combination and single therapy (25.6% [23 of 90] versus 27.8% [22 of 79]; adjusted HR, 0.87; 95% CI, 0.47 to 1.62; P = 0.660). These findings were consistent for 14-day all-cause mortality. In this large cohort, we found for the first time that combination therapy with beta-lactams and fluoroquinolones was associated with a reduction in 28-day all-cause mortality among less severely ill patients with bacteremia caused by gram-negative bacilli.

scholarly journals Prediabetes Defined by First Measured HbA1c Predicts Higher Cardiovascular Risk Compared With HbA1c in the Diabetes Range: A Cohort Study of Nationwide Registries

2021 ◽  
Author(s):  
Sam Kafai Yahyavi ◽  
Ole Snorgaard ◽  
Filip Krag Knop ◽  
Morten Schou ◽  
Christina Lee ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Cox Regression ◽  
Absolute Risk ◽  
Major Adverse Cardiovascular Events ◽  
Diagnostic Threshold ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
Design And Methods ◽  
Hba1c Measurement ◽  
First Time

Objective: To assess the risk of major adverse cardiovascular events (MACE), all-cause mortality, and initiation of medical treatment in subjects with prediabetes according to first-time measured HbA1c. <p>Research design and methods: Through registry databases, we identified 326,305 Danish patients with a first HbA1c between 40-51 mmol/mol (5.8-6.8%) from 2011 to 2017. After exclusion of patients with prior disease, 84,678 patients were followed 12 months after first HbA1c measurement. Cox regression models were used to estimate hazard ratios (HRs) of MACE and standardized absolute risks. Cumulative incidences were used to analyse initiation of glucose-lowering, anti-hypertensive, cholesterol-lowering and anti-thrombotic medication.</p> <p>Results: The 12-months risk of MACE and all-cause mortality increased gradually with increasing HbA1c until 47 mmol/mol (6.5%). Compared to HbA1c of 40-41 mmol/mol (5.8-5.9%), subjects with HbA1c of 46-47 mmol/mol (6.4-6.5%) had a 0.79% (95% CI 0.33-1.24) higher standardized absolute risk and a HR of 2.21 (95% CI 1.67-2.92) of MACE. Patients with a HbA1c of 48-49 mmol/mol (6.5-6.6%) had a -0.09% (95% CI -0.35-0.52) lower absolute risk and a HR of 1.33 (95% CI 0.87-2.05) of MACE. Initiation of medication was significantly lower among patients with HbA1c of 46-47 mmol/mol (6.4-6.5%) compared to patients with HbA1c of 48-49 mmol/mol (6.5-6.6%).</p> Conclusion: In the D<a>anish population screened for diabetes with HbA1c, the highest risk of MACE and all-cause mortality was found in subjects with HbA1c just below the diagnostic threshold for diabetes. Our results highlight the need for increased focus on the treatment of cardiovascular risk-factors in subjects with prediabetes.</a>

scholarly journals Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With Prosthetic Joint Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Sylvain Goutelle ◽  
Anne Conrad ◽  
Cécile Pouderoux ◽  
Evelyne Braun ◽  
Frédéric Laurent ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Case Series ◽  
Therapeutic Drug ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Gram Negative ◽  
Prosthetic Joint

Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study was to describe our approach and its first results in a case series. We analyzed data from patients who received suppressive antibiotic therapy by subcutaneous (SC) route with beta-lactams as salvage therapy for prosthetic joint infection (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and four men with a mean age of 77 years) were included from January 2017 to May 2020. The drugs administered by SC route were ceftazidime (n = 4), ertapenem (n = 4), and ceftriaxone (n = 2). In each patient, PK/PD-guided dosage individualization was performed based on TDM and minimum inhibitory concentration (MIC) measurements. The dose interval could be prolonged from twice daily to thrice weekly in some patients, while preserving the achievement of PK/PD targets. The infection was totally controlled by the strategy in nine out the 10 patients during a median follow-up of 1,035 days (~3 years). No patient acquired carbapenem-resistant Gram-negative bacteria during the follow-up. One patient presented treatment failure with acquired drug resistance under therapy, which could be explained by late MIC determination and insufficient exposure, retrospectively. To conclude, our innovative approach, based on model-based TDM, MIC determination, and individualized PK/PD goals, facilitates, and optimizes suppressive outpatient beta-lactam therapy administered by SC route for PJI. These encouraging results advocate for larger clinical evaluation.

scholarly journals Prediabetes Defined by First Measured HbA1c Predicts Higher Cardiovascular Risk Compared With HbA1c in the Diabetes Range: A Cohort Study of Nationwide Registries

2021 ◽  
Author(s):  
Sam Kafai Yahyavi ◽  
Ole Snorgaard ◽  
Filip Krag Knop ◽  
Morten Schou ◽  
Christina Lee ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Cox Regression ◽  
Absolute Risk ◽  
Major Adverse Cardiovascular Events ◽  
Diagnostic Threshold ◽  
Hazard Ratios ◽  
All Cause Mortality ◽  
Design And Methods ◽  
Hba1c Measurement ◽  
First Time

Objective: To assess the risk of major adverse cardiovascular events (MACE), all-cause mortality, and initiation of medical treatment in subjects with prediabetes according to first-time measured HbA1c. <p>Research design and methods: Through registry databases, we identified 326,305 Danish patients with a first HbA1c between 40-51 mmol/mol (5.8-6.8%) from 2011 to 2017. After exclusion of patients with prior disease, 84,678 patients were followed 12 months after first HbA1c measurement. Cox regression models were used to estimate hazard ratios (HRs) of MACE and standardized absolute risks. Cumulative incidences were used to analyse initiation of glucose-lowering, anti-hypertensive, cholesterol-lowering and anti-thrombotic medication.</p> <p>Results: The 12-months risk of MACE and all-cause mortality increased gradually with increasing HbA1c until 47 mmol/mol (6.5%). Compared to HbA1c of 40-41 mmol/mol (5.8-5.9%), subjects with HbA1c of 46-47 mmol/mol (6.4-6.5%) had a 0.79% (95% CI 0.33-1.24) higher standardized absolute risk and a HR of 2.21 (95% CI 1.67-2.92) of MACE. Patients with a HbA1c of 48-49 mmol/mol (6.5-6.6%) had a -0.09% (95% CI -0.35-0.52) lower absolute risk and a HR of 1.33 (95% CI 0.87-2.05) of MACE. Initiation of medication was significantly lower among patients with HbA1c of 46-47 mmol/mol (6.4-6.5%) compared to patients with HbA1c of 48-49 mmol/mol (6.5-6.6%).</p> Conclusion: In the D<a>anish population screened for diabetes with HbA1c, the highest risk of MACE and all-cause mortality was found in subjects with HbA1c just below the diagnostic threshold for diabetes. Our results highlight the need for increased focus on the treatment of cardiovascular risk-factors in subjects with prediabetes.</a>

Association between selenium intake, diabetes, and mortality in adults: findings from National Health and Nutrition Examination Survey (NHANES) 2003-2014

2021 ◽  
pp. 1-24
Author(s):  
Bushra Hoque ◽  
Zumin Shi
Keyword(s):  
National Health ◽  
Cox Regression ◽  
Inverse Association ◽  
Nutrition Examination Survey ◽  
Health And Nutrition ◽  
Hazard Ratios ◽  
The Us ◽  
All Cause Mortality ◽  
Cvd Mortality

Abstract Selenium (Se) is a trace mineral that has antioxidant and anti-inflammatory properties. This study aimed to investigate the association between Se intake, diabetes, all-cause and cause-specific mortality in a representative sample of US adults. Data from 18,932 adults who attended the 2003-2014 National Health and Nutrition Examination Survey (NHANES) were analysed. Information on mortality was obtained from the US mortality registry updated to 2015. Multivariable logistic regression and Cox regression were used. Cross-sectionally, Se intake was positively associated with diabetes. Comparing extreme quartiles of Se intake, the odds ratio (OR) for diabetes was 1.44 (95% CI: 1.09–1.89). During a mean of 6.6 years follow-up, there were 1627 death (312 CVD, 386 cancer). High intake of Se was associated with a lower risk of all-cause mortality. When comparing the highest with the lowest quartiles of Se intake, the hazard ratios (HRs) for all-cause, CVD mortality, cancer mortality and other mortality were: 0.77 (95% CI 0.59-1.01), 0.62 (95% CI, 0.35-1.13), 1.42 (95% CI, 0.78-2.58) and 0.60 (95% CI,0.40-0.80), respectively. The inverse association between Se intake and all-cause mortality was only found among white participants. In conclusion, Se intake was positively associated with diabetes but inversely associated with all-cause mortality. There was no interaction between Se intake and diabetes in relation to all-cause mortality.

scholarly journals Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia

2021 ◽  
Vol 79 (4) ◽  
pp. 1601-1612
Author(s):  
Johan Frederik Håkonsen Arendt ◽  
Erzsébet Horváth-Puhó ◽  
Henrik Toft Sørensen ◽  
Ebba Nexø ◽  
Lars Pedersen ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Vascular Dementia ◽  
Cox Regression ◽  
Population Based ◽  
High Dose ◽  
Plasma Vitamin ◽  
Hazard Ratios ◽  
B12 Deficiency ◽  
First Time

Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia. Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer’s disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes). Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000–2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200–600 pmol/L). We used multivariable Cox regression to compute 0–15-year hazard ratios for dementia. Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia. Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

scholarly journals Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as a risk factor for mortality in peruvian adults with chronic kidney disease.

2021 ◽  
Author(s):  
Gianfranco Umeres-Francia1 ◽  
María Rojas-Fernández ◽  
Percy Herrera Añazco ◽  
Vicente Benites-Zapata
Keyword(s):  
Risk Factor ◽  
Cox Regression ◽  
Outcome Variable ◽  
Lymphocyte Ratio ◽  
Hazard Ratios ◽  
Ckd Stage ◽  
All Cause Mortality ◽  
The Relationship ◽  
Crude Analysis

Objective: To assess the association between NLR and PLR with all-cause mortality in Peruvian patients with CKD Methods: We conducted a retrospective cohort study in adults with CKD in stages 1 to 5. The outcome variable was mortality and as variables of exposure to NLR and PLR. Both ratios were categorized as high with a cut-off point of 3.5 and 232.5; respectively. We carried out a Cox regression model and calculated crude and adjusted hazard ratios (HR) with their 95% confidence interval (95%CI). Results: We analyzed 343 participants with a median follow-up time of 2.45 years (2.08-3.08). The frequency of deaths was 17.5% (n=60). In the crude analysis, the high NLR and PLR were significantly associated with all-cause mortality (HR=2.01; 95% CI:1.11-3.66) and (HR=2.58; 95% CI:1.31-5.20). In the multivariate model, after adjusting for age, sex, serum creatinine, CKD stage, albumin and hemoglobin, the high NLR and PLR remained as an independent risk factor for all-cause mortality, (HR=2.10; 95% CI:1.11-3.95) and (HR=2.71; 95% CI:1.28-5.72). Conclusion: Our study suggests the relationship between high NLR and PLR with all-cause mortality in patients with CKD.

scholarly journals Intravenous Colistin Monotherapy versus Combination Therapy against Carbapenem-Resistant Gram-Negative Bacteria Infections: Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 7 (8) ◽  
pp. 208 ◽  
Author(s):  
I-Ling Cheng ◽  
Yu-Hung Chen ◽  
Chih-Cheng Lai ◽  
Hung-Jen Tang
Keyword(s):  
Combination Therapy ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Randomized Controlled ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
All Cause Mortality

This meta-analysis aims to compare intravenous colistin monotherapy and colistin-based combination therapy against carbapenem-resistant gram-negative bacteria (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July 2018. Only randomized controlled trials (RCTs) evaluating colistin alone and colistin-based combination therapy in the treatment of carbapenem-resistant GNB infections were included. The primary outcome was all-cause mortality. Five RCTs including 791 patients were included. Overall, colistin monotherapy was associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89–1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination therapy. The non-significant difference was also detected in infection-related mortality (RR, 1.23, 95% CI, 0.91–1.67, I2 = 0%) and microbiologic response (RR, 0.86, 95% CI, 0.72–1.04, I2 = 62%). In addition, no significant difference was observed in the subgroup analysis—high or low dose, with or without a loading dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination with rifampicin. Finally, colistin monotherapy was not associated with lower nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84–1.21, I2 = 0%). Based on the analysis of the five RCTs, no differences were found between colistin monotherapy and colistin-based combination therapy against carbapenem-resistant GNB infections, especially for A. baumannii infections.

Comparative Efficacy of Beta-Lactams and Macrolides in the Treatment of Pediatric Pneumonia: a Systematic Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia Al Saeedy ◽  
Syed Wasif Gillani ◽  
Jumana Al-Salloum ◽  
Arzu Moosvi ◽  
Mohamed Eissa ◽  
...  
Keyword(s):  
Systematic Review ◽  
Combination Therapy ◽  
Treatment Failure ◽  
Hospital Stay ◽  
Pediatric Population ◽  
Community Acquired Pneumonia ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Comparative Efficacy ◽  
Pediatric Pneumonia

Background: Pneumonia is an acute infection of the lung parenchyma that is differentiated among three main diagnoses: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and healthcare-associated pneumonia (HCAP). Though CAP is initially presented as a mild infection, it contributes to childhood mortality rates globally. A vast number of pathogens are the cause of CAP, but the two main causative organisms include Streptococcus pneumoniae and Haemophilus influenzae, with the former causing up to 50% of all childhood cases. Current treatment guidelines from the Infectious Diseases Society of America (IDSA), amoxicillin is the recommended treatment choice for mild-to-moderate CAP while ampicillin is recommended for cases of severe CAP. Previous studies compared treatment between macrolides and beta-lactams to provide more information on the effectiveness in the pediatric population. Objective: The objective of this article is to systematically review literature on comparative efficacy of beta-lactams and macrolides in the treatment of community-acquired pneumonia among children and to evaluate the outcomes that are used to determine drug efficacy in order to provide medication recommendations. Methods: A systematic literature search was conducted in PubMed, TRIP, Cochrane and SCOPUS. Cohort studies and randomized controlled trials between the years 2000 and 2020 that compared the efficacy of amoxicillin and macrolides in treating pediatric pneumonia are included in the systematic review Eligible patients included patients who were 17 years and younger, diagnosed with community-acquired pneumonia, and were given beta-lactams or macrolides, either as monotherapy or combination. Two reviewers were involved in the appraisal process to assess the quality of the methods used in the selected studies. Results: A total of six articles were eligible according to the inclusion criteria and quality assessment. Four articles compared beta-lactam monotherapy with beta-lactam and macrolide combination therapy, while Kogan R, et al. compared macrolide therapy monotherapy with beta-lactam and macrolide combination therapy and Leyenaar JK et al. compared ceftriaxone monotherapy to ceftriaxone plus macrolide combination therapy. The studies defined treatment failure as either a change in antibiotic therapy or hospital admission within 14 days of CAP diagnosis. Three studies used length of hospital stay as their primary outcome for comparison of treatment efficacy. Four studies showed that the use of macrolides provided better treatment outcomes by reducing hospital stay and treatment failure rates. Beta-lactam and macrolide combination therapy did not show a significant effect on treatment failure compared to beta-lactam monotherapy regimens and it did not affect mortality compared to placebo or diet alone. Within the macrolide class, azithromycin was more clinically significant compared to erythromycin. Conclusion: The use of macrolidesas monotherapy or add-on therapy to beta-lactams is more effective in the treatment of community acquired pneumonia in the pediatric population.

scholarly journals 751Investigation of the obesity paradox in kidney cancer: mystifying association or myth?

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Alicia Heath ◽  
Joanna Clasen ◽  
Elio Riboli ◽  
Ghislaine Scelo ◽  
David Muller
Keyword(s):  
Kidney Cancer ◽  
Cox Regression ◽  
Obesity Paradox ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Incidence And Mortality ◽  
All Cause Mortality ◽  
Using Data ◽  
Restricted Cubic Splines

Abstract Background An “obesity paradox” has been reported in kidney cancer, whereby obesity is a risk factor, yet appears to be associated with better survival. To evaluate this paradox, we investigated the association between pre-diagnostic adiposity and renal cell carcinoma (RCC) incidence and mortality. Methods Using data from 363,521 men and women in the European Prospective Investigation into Cancer and Nutrition (EPIC), Cox regression models yielded confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for RCC incidence and mortality in relation to BMI modelled continuously and using restricted cubic splines. RCC-specific and all-cause mortality were evaluated among cases. Results During a mean follow-up of 14.9 years, 936 incident RCC cases were identified, 383 of whom died (278 due to RCC). Each 5 kg/m2 increment in BMI was associated with 27% and 46% higher RCC incidence and mortality (HRs=1.27, 95% CI 1.18-1.37 and 1.46, 95% CI 1.28-1.66, respectively). Comparing a BMI of 35 with 22 kg/m2, HRs for RCC incidence and mortality were 1.88 (95% CI 1.54-2.30) and 2.37 (95% CI 1.68-3.35), respectively. Among RCC cases, HRs per 5 kg/m2 increment in BMI were 1.22 (95% CI 1.07-1.41) for RCC-specific mortality and 1.18 (95% CI 1.04-1.34) for all-cause mortality. Similar, positive linear associations were evident for waist circumference and waist-to-hip ratio. Conclusions Obesity was associated with increased RCC incidence and mortality, and worse prognosis among cases. Key messages The kidney cancer-obesity paradox does not appear to be real. Higher adiposity is associated with an increased risk of incident and fatal RCC.

Use of Antimicrobials and Toxicity

2019 ◽  
Author(s):  
Armine Sefton
Keyword(s):  
Immune System ◽  
Broad Spectrum ◽  
Therapeutic Index ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Gram Positive ◽  
Gram Negative ◽  
Narrow Spectrum ◽  
Source Of Infection ◽  
Bactericidal Agent

Broad-spectrum antibacterial agents kill most bacteria including gram-positive rods and cocci, gram-negative rods and cocci, and often anaerobes too. Narrow-spectrum agents kill a narrow range of microbes, e.g. benzylpenicillin is mainly active against gram-positive cocci. By and large a narrow-spectrum antimicrobial is less likely to disrupt a patient’s normal flora than a broad-spectrum agent. Hence, if the likely organism is causing an infection it is best to give a narrow-spectrum antimicrobial to treat that specific organism. If a patient presents ‘septic’ and the source of infection is unknown, relevant cultures should be taken followed by broad-spectrum antimicrobial cover. This can later be modified either when the source of infection is found or as a result of microbiology culture results. ● Agents mostly active against gram-positive bacteria include: ■ Penicillin (Also active against Neisseria spp.). ■ Fusidic acid. ■ Macrolides (Also active against Legionella, Campylobacter, Bordetella spp.). ■ Clindamycin. ■ Glycopeptides. ■ Oxazolidinones. ■ Streptogramins. ● Agents mainly active against gram-negative bacteria include: ■ Polymyxin. ■ Trimethoprim. ■ Aminoglycosides (also active against staphylococci and show synergy when combined with beta-lactams against/glycopeptides against streptococci). ■ Monobactams. ■ Temocillin. ● Broad-spectrum antimicrobials include: ■ Beta-lactam plus beta-lactamase inhibitor combinations. ■ Cephalosporins. ■ Carbapenems. ■ Chloramphenicol, Tetracyclines/Glycyclines. A bactericidal agent is a compound that actively kills multiplying bacteria. A bacteriostatic compound inhibits the growth of bacteria. Whether or not an antimicrobial is bactericidal or bacteriostatic depends on a variety of things, including the type of agent, its concentration, and the organism it is being used to treat. It is especially important to try and use a bactericidal agent if the patient’s immune system is impaired or the infection is at a site where it is difficult for the immune system to access, e.g. the heart valves in bacterial endocarditis, the meninges in meningitis. Examples of each are given here: ● Bactericidal agents include beta-lactams, glycopeptides, fluoroquinolones, and aminoglycosides. ● Bacteriostatic agents include macrolides, clindamycin, tetracyclines, trimethoprim, and sulphonamides. The therapeutic index of a drug is the ration of the concentration of drug likely to be toxic to the patient divided by the concentration of drug likely to be clinically effective.

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