Comparative review of combination therapy: two beta-lactams versus beta-lactam plus aminoglycoside

1986 ◽  
Vol 80 (6) ◽  
pp. 29-38 ◽  
Author(s):  
Pierre Dejace ◽  
Jean Klastersky
Keyword(s):  
Combination Therapy ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Comparative Review

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 Addition of Ceftaroline to Daptomycin after Emergence of Daptomycin-Nonsusceptible Staphylococcus aureus during Therapy Improves Antibacterial Activity

2012 ◽  
Vol 56 (10) ◽  
pp. 5296-5302 ◽  
Author(s):  
Warren E. Rose ◽  
Lucas T. Schulz ◽  
David Andes ◽  
Rob Striker ◽  
Andrew D. Berti ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Membrane Damage ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Bacterial Killing ◽  
Content Type ◽  
Cell Membrane Damage

ABSTRACTAntistaphylococcal beta-lactams enhance daptomycin activity and have been used successfully in combination for refractory methicillin-resistantStaphylococcus aureus(MRSA) infections. Ceftaroline possesses MRSA activity, but it is unknown if it improves the daptomycin potency comparably to other beta-lactams. We report a complex patient case of endocarditis who was treated with daptomycin in combination with ceftaroline, which resulted in clearance of a daptomycin-nonsusceptible strain. Anin vitropharmacokinetic/pharmacodynamic model of renal failure was used to simulate the development of daptomycin resistance and evaluate the microbiologic effects of daptomycin plus ceftaroline treatment. Combination therapy with daptomycin and ceftaroline restored daptomycin sensitivityin vivoand resulted in clearance of persistent blood cultures. Daptomycin susceptibilityin vitrowas increased in the presence of either ceftaroline or oxacillin. Daptomycin at 6 mg/kg of body weight every 48 h was bactericidal in the model but resulted in regrowth and daptomycin resistance (MIC, 2 to 4 μg/ml) with continued monotherapy. The addition of ceftaroline at 200 mg every 12 h after the emergence of daptomycin resistance enhanced bacterial killing. Importantly, daptomycin plus ceftaroline as the initial combination therapy produced rapid and sustained bactericidal activity and prevented daptomycin resistance. Bothin vivo- andin vitro-derived daptomycin resistance resulted in bacteria with more fluid cell membranes. After ceftaroline was added in the model, fluidity was restored to the level of the initialin vivoisolate. Daptomycin-resistant isolates required high daptomycin exposures (at least 10 mg/kg) to optimize cell membrane damage with daptomycin alone. Ceftaroline combined with daptomycin was effective in eliminating daptomycin-resistant MRSA, and these results further justify the potential use of daptomycin plus beta-lactam therapy for these refractory infections.

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.

What do beta-lactams add to vancomycin or daptomycin in the treatment of patients with methicillin-resistant Staphylococcus aureus bacteraemia? A review

2021 ◽  
pp. postgradmedj-2020-139512
Author(s):  
Laura García Aragonés ◽  
José Javier Blanch Sancho ◽  
Juan Carlos Segura Luque ◽  
Fernando Mateos Rodriguez ◽  
Elisa Martínez Alfaro ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Systematic Reviews ◽  
Observational Studies ◽  
Combined Treatment ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Methicillin Resistant ◽  
Significant Difference

Several studies have documented the synergy between vancomycin/daptomycin and various beta-lactams, and clinical studies have studied this combination therapy in humans. We review the published literature on this topic to know the utility of the combined treatment with beta-lactams in treating bacteraemia methicillin-resistant Staphylococcus aureus (MRSA) infections. Fifteen observational studies, three randomised clinical trials and three systematics reviews are analysed in this article. Observational studies used ceftaroline, cefazolin, piperacillin/tazobactam or cefepime among the beta-lactams. Clinical trials used cloxacillin or flucloxacillin as the most used beta-lactam in two trials and ceftaroline in one. Three systematic reviews are published. One of them only includes studies with vancomycin and included six studies. The other two systematic reviews include patients with daptomycin or vancomycin and included 15 and 9 studies, respectively. Adding a beta-lactam to vancomycin or daptomycin may help shorten bacteraemia and avoid recurrences in patients with MRSA bacteraemia. There is no evidence that combined therapy improves mortality. Nephrotoxicity in clinical trials precludes the use of combination therapy mainly with cloxacillin or flucloxacillin, but systematic reviews have not found a significant difference in this point in observational studies with other beta-lactams. The role of other beta-lactams such as ceftaroline should be thoroughly studied in these patients.

scholarly journals Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

2021 ◽  
Vol 9 (7) ◽  
pp. 1505
Author(s):  
Claire Roger ◽  
Benjamin Louart
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Clinical Manifestations ◽  
Acute Interstitial Nephritis ◽  
Convulsive Status Epilepticus ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Drug Induced ◽  
Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

Confronting the Challenge of Beta-Lactam Allergies: A Quasi-Experimental Study Assessing Impact of Pharmacy-Led Interventions

2017 ◽  
Vol 32 (2) ◽  
pp. 139-146 ◽  
Author(s):  
Steven C. Krey ◽  
Jeff Waise ◽  
Lee P. Skrupky
Keyword(s):  
Guideline Implementation ◽  
Tertiary Care ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Antibiotic Selection ◽  
Reaction Type ◽  
Care Community ◽  
Multidisciplinary Education ◽  
Quasi Experimental ◽  
Pharmacy Technicians

Objective: To improve allergy history documentation and increase the use of beta-lactams when appropriate in patients with a reported beta-lactam allergy. Methods: This pre–post study was conducted at a 167-bed tertiary care community hospital and evaluated multidisciplinary interventions on allergy documentation and antibiotic selection. Interventions included education, creation of local practice guidelines, and modified practices for pharmacists and pharmacy technicians. Inpatients with a reported beta-lactam allergy receiving at least 1 antibiotic for >24 hours were included; first admissions were assessed. Primary outcomes were documentation of reaction type and percentage of patients receiving non-beta-lactam therapy. Secondary outcomes included documentation of previously tolerated beta-lactams, modification of non-beta-lactam therapy, discharge antibiotics, and adverse reactions. Results: A total of 179 patients were included, 91 preintervention and 88 postintervention. No significant differences were observed between the before versus after groups in the percentage of patients with documentation of reaction type (90.1% vs 89.8%, P = .940) or the overall percentage of patients receiving non-beta-lactams (86.8% vs 84.1%, P = .605). However, significantly more patients in the after phase had documentation of previously tolerated beta-lactams (8.8% vs 28.4%, P = .001), and among patients receiving a non-beta-lactam, a greater percentage was subsequently switched to a beta-lactam (11.4% vs 25.7%, P = .022). One allergic reaction was documented during the study, which occurred in the before phase. Conclusion: Multidisciplinary education and local guideline implementation led by pharmacists may improve allergy documentation and antibiotic selection in patients with reported beta-lactam allergies.

scholarly journals Influence of Reported Penicillin Allergy on Mortality in MSSA Bacteremia

2018 ◽  
Vol 5 (3) ◽  
Author(s):  
Nicholas A Turner ◽  
Rebekah Moehring ◽  
Christina Sarubbi ◽  
Rebekah H Wrenn ◽  
Richard H Drew ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Multivariable Analysis ◽  
Mortality Rates ◽  
Penicillin Allergy ◽  
Care Hospital ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Appropriate Treatment ◽  
Large Tertiary Care ◽  
Multivariable Regression Models

Abstract Background Penicillin allergy frequently impacts antibiotic choice. As beta-lactams are superior to vancomycin in treating methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, we examined the effect of reported penicillin allergy on clinical outcomes in patients with MSSA bacteremia. Methods In this retrospective cohort study of adults with MSSA bacteremia admitted to a large tertiary care hospital, outcomes were examined according to reported penicillin allergy. Primary outcomes included 30-day and 90-day mortality rates. Multivariable regression models were developed to quantify the effect of reported penicillin allergy on mortality while adjusting for potential confounders. Results From 2010 to 2015, 318 patients with MSSA bacteremia were identified. Reported penicillin allergy had no significant effect on adjusted 30-day mortality (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.29–1.84; P = .51). Patients with reported penicillin allergy were more likely to receive vancomycin (38% vs 11%, P &lt; .01), but a large number received cefazolin regardless of reported allergy (29 of 66, 44%). Mortality rates were highest among nonallergic patients receiving vancomycin (22.6% vs 7.4% for those receiving beta-lactams regardless of reported allergy, P &lt; .01). In multivariable analysis, beta-lactam receipt was most strongly associated with survival (OR, 0.26; 95% CI, 0.12–0.54). Conclusions Reported penicillin allergy had no significant effect on 30- or 90-day mortality. Non-penicillin-allergic patients receiving vancomycin for treatment of MSSA bacteremia had the highest mortality rates overall. Receipt of a beta-lactam was the strongest predictor of survival. These results underscore the importance of correct classification of patients with penicillin allergy and appropriate treatment with a beta-lactam when tolerated.

scholarly journals Antipneumococcal activity of BAY 12-8039, a new quinolone, compared with activities of three other quinolones and four oral beta-lactams.

1997 ◽  
Vol 41 (12) ◽  
pp. 2786-2789 ◽  
Author(s):  
M A Visalli ◽  
M R Jacobs ◽  
P C Appelbaum
Keyword(s):  
Beta Lactam ◽  
Beta Lactams ◽  
Agar Dilution ◽  
Resistant Strains

Activities of BAY 12-8039 against 205 pneumococci were tested by agar dilution. MICs (in micrograms per milliliter) at which 50 and 90% of the isolates are inhibited (MIC50s and MIC90s, respectively) were 0.125 and 0.25 (BAY 12-8039), 2.0 and 4.0 (ciprofloxacin and ofloxacin), and 0.25 and 0.5 (sparfloxacin). Beta-lactam MIC50s and MIC90s for penicillin-susceptible, -intermediate, and -resistant strains, in that order, were 0.016 and 0.03, 0.25 and 2.0, and 2.0 and 4.0 (amoxicillin); 0.03 and 0.06, 0.25 and 4.0, and 4.0 and 8.0 (ampicillin); 0.03 and 0.06, 0.5 and 4.0, and 4.0 and 8.0 (cefuroxime); and 0.03 and 0.125, 0.25 and 2.0, and 4.0 and 8.0 (cefpodoxime). At two times their MICs after 24 h, BAY 12-8039, ciprofloxacin, ampicillin, and cefuroxime were uniformly bactericidal (99.9% killing) against 12 strains; other compounds were bactericidal at four times their MICs.

scholarly journals Could Dampening Expression of theNeisseria gonorrhoeaemtrCDE-Encoded Efflux Pump Be a Strategy To Preserve Currently or Resurrect Formerly Used Antibiotics To Treat Gonorrhea?

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Shaochun Chen ◽  
Kristie L. Connolly ◽  
Corinne Rouquette-Loughlin ◽  
Alexander D’Andrea ◽  
Ann E. Jerse ◽  
...  
Keyword(s):  
Genital Tract ◽  
Efflux Pump ◽  
Health Concern ◽  
Third Generation ◽  
Global Public Health ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Genital Tract Infection ◽  
Infected Female ◽  
Content Type

ABSTRACTNeisseria gonorrhoeaehas developed resistance to every antibiotic introduced for treatment of gonorrhea since 1938, and concern now exists that gonorrheal infections may become refractory to all available antibiotics approved for therapy. The current recommended dual antibiotic treatment regimen of ceftriaxone (CRO) and azithromycin (AZM) is threatened with the emergence of gonococcal strains displaying resistance to one or both of these antibiotics. Non-beta-lactamase resistance to penicillin and third-generation cephalosporins, as well as low-level AZM resistance expressed by gonococci, requires overexpression of themtrCDE-encoded efflux pump, which in wild-type (WT) strains is subject to transcriptional repression by MtrR. Since earlier studies showed that loss of MtrCDE renders gonococci hypersusceptible to beta-lactams and macrolides, we hypothesized that transcriptional dampening ofmtrCDEwould render an otherwise resistant strain susceptible to these antibiotics as assessed by antibiotic susceptibility testing and during experimental infection. In order to test this hypothesis, we ectopically expressed a WT copy of themtrRgene, which encodes the repressor of themtrCDEefflux pump operon, inN. gonorrhoeaestrain H041, the first reported gonococcal strain to cause a third-generation-cephalosporin-resistant infection. We now report that MtrR production can repress the expression ofmtrCDE, increase antimicrobial susceptibilityin vitro, and enhance beta-lactam efficacy in eliminating gonococci as assessed in a female mouse model of lower genital tract infection. We propose that strategies that target the MtrCDE efflux pump should be considered to counteract the increasing problem of antibiotic-resistant gonococci.IMPORTANCEThe emergence of gonococcal strains resistant to past or currently used antibiotics is a global public health concern, given the estimated 78 million infections that occur annually. The dearth of new antibiotics to treat gonorrhea demands that alternative curative strategies be considered to counteract antibiotic resistance expressed by gonococci. Herein, we show that decreased expression of a drug efflux pump that participates in gonococcal resistance to antibiotics can increase gonococcal susceptibility to beta-lactams and macrolides under laboratory conditions, as well as improve antibiotic-mediated clearance of gonococci from the genital tract of experimentally infected female mice.

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