scholarly journals Beta Lactams plus Daptomycin Combination Therapy for Infective Endocarditis: An Italian National Survey (BADAS)

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 56
Author(s):  
Silvia Corcione ◽  
Tommaso Lupia ◽  
Carlo Pallotto ◽  
Daniele Roberto Giacobbe ◽  
Ilaria De Benedetto ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Combination Therapy ◽  
National Survey ◽  
Severe Disease ◽  
Combination Regimen ◽  
Beta Lactams ◽  
First Line ◽  
Cross Sectional ◽  
Bacterial Killing ◽  
Feasible Option

Background: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. Methods: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. Results: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. Conclusions: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin.

scholarly journals Rational deployment of antimalarial drugs in Africa: should first-line combination drugs be reserved for paediatric malaria cases?

Parasitology ◽  
2011 ◽  
Vol 138 (12) ◽  
pp. 1459-1468 ◽  
Author(s):  
COLIN J. SUTHERLAND ◽  
HAMZA BABIKER ◽  
MARGARET J. MACKINNON ◽  
LISA RANFORD-CARTWRIGHT ◽  
BADRIA BABIKER EL SAYED
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Selective Pressure ◽  
Severe Disease ◽  
Preventive Therapy ◽  
Combination Regimen ◽  
First Line ◽  
Drug Pressure ◽  
Paediatric Malaria ◽  
Parasite Populations

SUMMARYArtemisinin-based combination therapy is exerting novel selective pressure upon populations of Plasmodium falciparum across Africa. Levels of resistance to non-artemisinin partner drugs differ among parasite populations, and so the artemisinins are not uniformly protected from developing resistance, already present in South East Asia. Here, we consider strategies for prolonging the period of high level efficacy of combination therapy for two particular endemicities common in Africa. Under high intensity transmission, two alternating first-line combinations, ideally with antagonistic selective effects on the parasite genome, are advocated for paediatric malaria cases. This leaves second-line and other therapies for adult cases, and for intermittent preventive therapy. The drug portfolio would be selected to protect the ‘premier’ combination regimen from selection for resistance, while maximising impact on severe disease and mortality in children. In endemic areas subject to low, seasonal transmission of Plasmodium falciparum, such a strategy may deliver little benefit, as children represent a minority of cases. Nevertheless, the deployment of other drug-based interventions in low transmission and highly seasonal areas, such as mass drug administration aimed to interrupt malaria transmission, or intermittent preventive therapy, does provide an opportunity to diversify drug pressure. We thus propose an integrated approach to drug deployment, which minimises direct selective pressure on parasite populations from any one drug component. This approach is suitable for qualitatively and quantitatively different burdens of malaria, and should be supported by a programme of routine surveillance for emerging resistance.

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 THE CURRENT SITUATION OF USING DRUGS FOR HYPERTENSION OUTPATIENTS

2021 ◽  
Vol 62 (2) ◽  
Author(s):  
Bùi Tùng Hiệp ◽  
Nguyễn Thị Xuân Hoàng ◽  
Đỗ Văn Mãi ◽  
Nguyễn Đức Lộc
Keyword(s):  
Combination Therapy ◽  
Drug Interactions ◽  
Calcium Channel ◽  
General Hospital ◽  
Calcium Channel Blockers ◽  
Current Situation ◽  
Combination Regimen ◽  
Channel Blockers ◽  
Cross Sectional ◽  
Calcium Blockers

Objectives: To assess the current situation of using hypertension drugs for outpatients at the examination department of Hau Nghia Regional General Hospital - Long An. Objects and methods: Study of Cross-sectional description, retrospection, non-intervention on 180 patients who came to examine and treat hypertension at the examination Department, stored on the software of the Hau Nghia Regional General Hospital - Long An. Results: Among the drug groups used to treat hypertension, the group of drugs used the most was calcium channel blockers (58.25%), the lowest was diuretics with 3.88%. The regimens used for patients, the number of regimens using one drug accounted for the largest proportion, accounting for 86.67%. The regimen using 2 drugs accounted for 12.22% and the lowest was the combination regimen of 3 drugs with only 2 patients, accounting for 1.11%. In monotherapy was preferred by the doctor over combination therapy, in which Amlodipine was the most prescribed drug. The number of times of drug use per day of some drugs did not comply with recommendations and drug interactions accounted for a high proportion. Conclusion: The treatment regimen of hypertension was mainly monotherapy with calcium blockers, the most common being Amlodipine. However, the number of drugs used per day of some drugs did not comply with recommendations and drug interactions accounted for a high proportion.

scholarly journals Beyond a single pathway: combination therapy in pulmonary arterial hypertension

2016 ◽  
Vol 25 (142) ◽  
pp. 408-417 ◽  
Author(s):  
Olivier Sitbon ◽  
Sean Gaine
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Arterial Hypertension ◽  
Triple Therapy ◽  
Severe Disease ◽  
Dual Therapy ◽  
Disease Stage ◽  
Combination Regimen ◽  
Initial Regimen ◽  
Pulmonary Arterial

There is a strong rationale for combining therapies to simultaneously target three of the key pathways implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Evidence to support this strategy is growing, and a number of studies have demonstrated that combination therapy, administered as either a sequential or an initial regimen, can improve long-term outcomes in PAH. Dual combination therapy with a phosphodiesterase-5 inhibitor and an endothelin receptor antagonist is the most widely utilised combination regimen. However, some patients fail to achieve their treatment goals on dual therapy and may benefit from the addition of a third drug. The use of triple therapy in clinical practice was previously reserved for patients with severe disease due to the need for parenteral administration of prostanoids. Although triple therapy with parenteral prostanoids plays a key role in the management of severe PAH, the approval of oral therapies that target the prostacyclin pathway means that all three pathways can now be targeted with oral drugs at an earlier disease stage. Furthermore, there is evidence demonstrating that this approach can delay disease progression. Based on the evidence available, it is becoming increasingly clear that all PAH patients should be offered the benefits of combination therapy.

scholarly journals Evaluating mono and combination therapy of meropenem and amikacin against Pseudomonas aeruginosa bacteremia in the Hollow-Fiber Infection Model

2021 ◽  
Author(s):  
Minyon L Avent ◽  
Kate L. McCarthy ◽  
Fekade Sime ◽  
saiyuri naicker ◽  
Aaron James Heffernan ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Hollow Fiber ◽  
Day Treatment ◽  
Infection Model ◽  
Combination Regimen ◽  
Bacterial Killing ◽  
Initial Inoculum ◽  
Potential Synergy

Debate continues as to the role of combination antibiotic therapy for the management of Pseudomonas aeruginosa infections. We studied extent of bacterial killing and resistance emergence of meropenem and amikacin as monotherapy and as a combination therapy against susceptible and resistant P. aeruginosa isolates from bacteremic patients using the dynamic in vitro hollow-fiber infection model. Three P. aeruginosa isolates (meropenem MICs 0.125, 0.25 & 64 mg/L) were used simulating bacteremia with an initial inoculum ~ 1×105 CFU/mL and the expected pharmacokinetics of meropenem and amikacin in critically ill patients. For isolates susceptible to amikacin and meropenem (isolates 1 and 2), the rate of bacterial killing was increased with the combination regimen when compared with monotherapy of either antibiotic. Both the combination and meropenem monotherapy were able to sustain bacterial killing throughout the seven-day treatment course, whereas regrowth of bacteria occurred with amikacin monotherapy after 12 hours. For the meropenem-resistant P. aeruginosa isolate (isolate 3), only the combination regimen demonstrated bacterial killing. Given that tailored antibiotic regimens can maximize potential synergy against some isolates, future studies should explore the benefit of combination therapy against resistant P. aeruginosa.

scholarly journals Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049967
Author(s):  
Karen Sól Saevarsdóttir ◽  
Hildur Ýr Hilmarsdóttir ◽  
Ingibjörg Magnúsdóttir ◽  
Arna Hauksdóttir ◽  
Edda Bjork Thordardottir ◽  
...  
Keyword(s):  
Severe Disease ◽  
Symptom Burden ◽  
Cross Sectional Study ◽  
Illness Severity ◽  
University Education ◽  
Adjusted Relative Risk ◽  
Sectional Study ◽  
Cross Sectional ◽  
Symptoms Of Depression ◽  
Increased Risk

ObjectiveTo test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

scholarly journals Symptom cluster is associated with prolonged return-to-play in symptomatic athletes with acute respiratory illness (including COVID-19): a cross-sectional study—AWARE study I

2021 ◽  
pp. bjsports-2020-103782
Author(s):  
Martin Schwellnus ◽  
Nicola Sewry ◽  
Carolette Snyders ◽  
Kelly Kaulback ◽  
Paola Silvia Wood ◽  
...  
Keyword(s):  
Online Survey ◽  
Severe Disease ◽  
Univariate Analysis ◽  
Respiratory Illness ◽  
Symptom Cluster ◽  
Return To Play ◽  
Whole Body ◽  
Multiple Model ◽  
Acute Respiratory Illness ◽  
Cross Sectional

BackgroundThere are no data relating symptoms of an acute respiratory illness (ARI) in general, and COVID-19 specifically, to return to play (RTP).ObjectiveTo determine if ARI symptoms are associated with more prolonged RTP, and if days to RTP and symptoms (number, type, duration and severity) differ in athletes with COVID-19 versus athletes with other ARI.DesignCross-sectional descriptive study.SettingOnline survey.ParticipantsAthletes with confirmed/suspected COVID-19 (ARICOV) (n=45) and athletes with other ARI (ARIOTH) (n=39).MethodsParticipants recorded days to RTP and completed an online survey detailing ARI symptoms (number, type, severity and duration) in three categories: ‘nose and throat’, ‘chest and neck’ and ‘whole body’. We report the association between symptoms and RTP (% chance over 40 days) and compare the days to RTP and symptoms (number, type, duration and severity) in ARICOV versus ARIOTH subgroups.ResultsThe symptom cluster associated with more prolonged RTP (lower chance over 40 days; %) (univariate analysis) was ‘excessive fatigue’ (75%; p<0.0001), ‘chills’ (65%; p=0.004), ‘fever’ (64%; p=0.004), ‘headache’ (56%; p=0.006), ‘altered/loss sense of smell’ (51%; p=0.009), ‘Chest pain/pressure’ (48%; p=0.033), ‘difficulty in breathing’ (48%; p=0.022) and ‘loss of appetite’ (47%; p=0.022). ‘Excessive fatigue’ remained associated with prolonged RTP (p=0.0002) in a multiple model. Compared with ARIOTH, the ARICOV subgroup had more severe disease (greater number, more severe symptoms) and more days to RTP (p=0.0043).ConclusionSymptom clusters may be used by sport and exercise physicians to assist decision making for RTP in athletes with ARI (including COVID-19).

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