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1.
Ther Drug Monit ; 43(4): 451-454, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1501177

ABSTRACT

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefepime/pharmacokinetics , Critical Illness/therapy , Drug Dosage Calculations , Precision Medicine/methods , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Cefepime/administration & dosage , Cefepime/adverse effects , Humans , Male , Middle Aged
3.
Drug Des Devel Ther ; 15: 3349-3378, 2021.
Article in English | MEDLINE | ID: covidwho-1352763

ABSTRACT

Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable.


Subject(s)
Ambulatory Care , Anti-Bacterial Agents/therapeutic use , COVID-19 , Gram-Positive Bacterial Infections/drug therapy , Off-Label Use , Patient Participation , Teicoplanin/analogs & derivatives , Algorithms , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Clinical Decision-Making , Decision Support Techniques , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Humans , Teicoplanin/adverse effects , Teicoplanin/pharmacokinetics , Teicoplanin/therapeutic use , Treatment Outcome
4.
Int J Antimicrob Agents ; 58(4): 106409, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330851

ABSTRACT

Since the start of the COVID-19 pandemic, there has been concern about the concomitant rise of antimicrobial resistance. While bacterial co-infections seem rare in COVID-19 patients admitted to hospital wards and intensive care units (ICUs), an increase in empirical antibiotic use has been described. In the ICU setting, where antibiotics are already abundantly-and often inappropriately-prescribed, the need for an ICU-specific antimicrobial stewardship programme is widely advocated. Apart from essentially warning against the use of antibacterial drugs for the treatment of a viral infection, other aspects of ICU antimicrobial stewardship need to be considered in view of the clinical course and characteristics of COVID-19. First, the distinction between infectious and non-infectious (inflammatory) causes of respiratory deterioration during an ICU stay is difficult, and the much-debated relevance of fungal and viral co-infections adds to the complexity of empirical antimicrobial prescribing. Biomarkers such as procalcitonin for the decision to start antibacterial therapy for ICU nosocomial infections seem to be more promising in COVID-19 than non-COVID-19 patients. In COVID-19 patients, cytomegalovirus reactivation is an important factor to consider when assessing patients infected with SARS-CoV-2 as it may have a role in modulating the patient immune response. The diagnosis of COVID-19-associated invasive aspergillosis is challenging because of the lack of sensitivity and specificity of the available tests. Furthermore, altered pharmacokinetic/pharmacodynamic properties need to be taken into account when prescribing antimicrobial therapy. Future research should now further explore the 'known unknowns', ideally with robust prospective study designs.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/methods , COVID-19 , Cross Infection/diagnosis , Anti-Bacterial Agents/pharmacokinetics , Antimicrobial Stewardship/organization & administration , Biomarkers/analysis , COVID-19/drug therapy , Coinfection/drug therapy , Coinfection/microbiology , Cross Infection/drug therapy , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/virology , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Virus Activation/drug effects
5.
Ther Drug Monit ; 43(4): 451-454, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1197045

ABSTRACT

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefepime/pharmacokinetics , Critical Illness/therapy , Drug Dosage Calculations , Precision Medicine/methods , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Cefepime/administration & dosage , Cefepime/adverse effects , Humans , Male , Middle Aged
6.
Drug Deliv Transl Res ; 11(4): 1340-1351, 2021 08.
Article in English | MEDLINE | ID: covidwho-1047033

ABSTRACT

Infectious diseases, such as the coronavirus disease-19, SARS virus, Ebola virus, and AIDS, threaten the health of human beings globally. New viruses, drug-resistant bacteria, and fungi continue to challenge the human efficacious drug bank. Researchers have developed a variety of new antiviral and antibacterial drugs in response to the infectious disease crisis. Meanwhile, the development of functional materials has also improved therapeutic outcomes. As a natural material, chitosan possesses good biocompatibility, bioactivity, and biosafety. It has been proven that the cooperation between chitosan and traditional medicine greatly improves the ability of anti-infection. This review summarized the application and design considerations of chitosan-composed systems for the treatment of infectious diseases, looking forward to providing the idea of infectious disease therapy.


Subject(s)
Anti-Infective Agents/administration & dosage , Biocompatible Materials/administration & dosage , COVID-19/drug therapy , Chitosan/administration & dosage , Communicable Diseases/drug therapy , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/immunology , Anti-Bacterial Agents/pharmacokinetics , Anti-Infective Agents/immunology , Anti-Infective Agents/pharmacokinetics , Bandages/microbiology , Biocompatible Materials/pharmacokinetics , COVID-19/immunology , COVID-19/metabolism , Chitosan/immunology , Chitosan/pharmacokinetics , Communicable Diseases/immunology , Communicable Diseases/metabolism , Humans , Wound Healing/drug effects , Wound Healing/physiology
7.
Antivir Chem Chemother ; 28: 2040206620961712, 2020.
Article in English | MEDLINE | ID: covidwho-797242

ABSTRACT

Macrolides are a large group of antibiotics characterised by the presence of a macro-lactone ring of variable size. The prototype of macrolide antibiotics, erythromycin was first produced by Streptomyces and associated species more than half a century ago; other related drugs were developed. These drugs have been shown to have several pharmacological properties: in addition to their antibiotic activity, they possess some anti-inflammatory properties and have been also considered against non-bacterial infections. In this review, we analysed the available clinical evidences regarding the potential anti-viral activity of macrolides, by focusing on erythromycin, clarithromycin and azithromycin. Overall, there is no significant evidences so far that macrolides might have a direct benefit on most of viral infections considered in this review (RSV, Influenza, coronaviruses, Ebola and Zika viruses). However, their clinical benefit cannot be ruled out without further and focused clinical studies. Macrolides may improve the clinical course of viral respiratory infections somehow, at least through indirect mechanisms relying on some and variable anti-inflammatory and/or immunomodulatory effects, in addition to their well-known antibacterial activity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Coronavirus Infections/drug therapy , Macrolides/pharmacology , Pneumonia, Viral/drug therapy , Animals , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/pharmacokinetics , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Humans , Macrolides/pharmacokinetics , Macrolides/therapeutic use , Pandemics , SARS-CoV-2
9.
CPT Pharmacometrics Syst Pharmacol ; 9(8): 435-443, 2020 08.
Article in English | MEDLINE | ID: covidwho-574626

ABSTRACT

Azithromycin (AZ), a broad-spectrum macrolide antibiotic, is being investigated in patients with coronavirus disease 2019 (COVID-19). A population pharmacokinetic model was implemented to predict lung, intracellular poly/mononuclear cell (peripheral blood monocyte (PBM)/polymorphonuclear leukocyte (PML)), and alveolar macrophage (AM) concentrations using published data and compared against preclinical effective concentration 90% (EC90 ) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The final model described the data reported in eight publications adequately. Consistent with its known properties, concentrations were higher in AM and PBM/PML, followed by lung tissue, and lowest systemically. Simulated PBM/PML concentrations exceeded EC90 following the first dose and for ~ 14 days following 500 mg q.d. for 3 days or 500 mg q.d. for 1 day/250 mg q.d. on days 2-5, 10 days following a single 1,000 mg dose, and for > 20 days with 500 mg q.d. for 10 days. AM concentrations exceeded the 90% inhibitory concentration for > 20 days for all regimens. These data will better inform optimization of dosing regimens for AZ clinical trials.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Azithromycin/administration & dosage , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Anti-Bacterial Agents/pharmacokinetics , Azithromycin/pharmacokinetics , COVID-19 , Dose-Response Relationship, Drug , Humans , Leukocytes, Mononuclear/metabolism , Lung/metabolism , Macrophages, Alveolar/metabolism , Models, Biological , Neutrophils/metabolism , Pandemics , Tissue Distribution
10.
Ther Drug Monit ; 42(2): 165-168, 2020 04.
Article in English | MEDLINE | ID: covidwho-11505

ABSTRACT

BACKGROUND: Dalbavancin, albeit indicated for the treatment of skin structure infections, is used for a much wider range of infections. This drug is characterized by a long half-life (more than 200 hours), a favorable safety profile, and an activity against a wide array of gram-positive organisms, including several strains of Staphylococci and Enterococci. METHODS: In this study, we presented 3 cases of critically ill patients treated with dalbavancin. All patients were therapeutically monitored for plasma dalbavancin concentrations; ultrafiltrate dalbavancin concentrations were assessed in a patient undergoing continuous renal-replacement therapy. Dalbavancin concentrations were measured using a validated liquid chromatographic method coupled with mass spectrometry. RESULTS: All 3 severely ill patients experiencing necrotizing fasciitis were successfully treated during the acute phase with dalbavancin. Dalbavancin clearance in patient 3 (0.334 L/h) was considerably increased compared with values measured in the other 2 patients (0.054 and 0.075 L/h) and with data reported in the literature (0.04-0.06 L/h). CONCLUSIONS: Our case reports presented preliminary evidence that dalbavancin can be considered a therapeutic option for necrotizing fasciitis in intensive care unit patients. The role of hypoalbuminemia during dalbavancin exposure merits further investigation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Critical Illness , Drug Monitoring/methods , Fasciitis, Necrotizing/drug therapy , Teicoplanin/analogs & derivatives , Adult , Anti-Bacterial Agents/pharmacokinetics , Half-Life , Humans , Male , Metabolic Clearance Rate , Microbial Sensitivity Tests , Middle Aged , Severity of Illness Index , Teicoplanin/pharmacokinetics , Teicoplanin/therapeutic use
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