zithromax and Hyperglycemia

Coronavirus disease-2019 (COVID-19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin-converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS-CoV-2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS-CoV-2 in COVID-19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID-19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS-CoV-2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.

Topics: Angiotensin-Converting Enzyme 2; Antibodies, Neutralizing; Antibody-Dependent Cell Cytotoxicity; Antiviral Agents; Azithromycin; Betacoronavirus; Coronavirus Infections; COVID-19; Glucose; Glycosylation; Host-Pathogen Interactions; Humans; Hydroxychloroquine; Hyperglycemia; Incidence; Macrophages; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus

To assess the prevalence of dysglycemia (hypoglycemia or hyperglycemia) associated with oral levofloxacin and gatifloxacin therapy in an outpatient setting, and to determine the characteristics of patients who developed dysglycemia while receiving either fluoroquinolone.. Retrospective medical record review.. Outpatient clinic of a Veterans Affairs teaching hospital.. A total of 1573 patients who received oral levofloxacin (343 patients), gatifloxacin (589 patients), or azithromycin (as a control, 641 patients) between June 1, 2004, and May 31, 2006.. Dysglycemia occurred in 33 patients: 13 (2.2%), 9 (2.6%), and 11 (1.7%), respectively, of those in the gatifloxacin, levofloxacin, and azithromycin groups. Of 13 patients who experienced a hyperglycemic event, 11 (84.6%) had diabetes mellitus. After adjustment for confounding factors, neither levofloxacin nor gatifloxacin were associated with increased odds of developing a dysglycemic event compared with azithromycin. Multivariate analysis demonstrated that lack of downward dosage adjustment based on creatinine clearance (odds ratio [OR] 10.3, 95% confidence interval [CI] 3.8-27.6), presence of diabetes (OR 17.1, 95% CI 3.1-94.9), or treatment with insulin (OR 5.3, 95% CI 1.8-15.7) or sulfonylureas (OR 3.6, 95% CI 1.3-10.4) independently increased dysglycemia risk. Obesity (body mass index > or = 30 kg/m(2)) was independently protective (OR 0.22, 95% CI 0.09-0.55) against dysglycemic events.. Levofloxacin and gatifloxacin were not significantly associated with increased dysglycemic events compared with azithromycin. Lack of downward fluoroquinolone dosage adjustment for renal function, presence of diabetes, and treatment with insulin or sulfonylureas each independently increased the risk of dysglycemia. Obesity was independently protective against dysglycemia. More data are needed on the contributing effects of diabetes, fluoroquinolone dosage, and concomitant drug therapy so that an appropriate risk-management strategy can be developed.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azithromycin; Creatinine; Diabetes Complications; Female; Fluoroquinolones; Gatifloxacin; Hospitals, Veterans; Humans; Hyperglycemia; Hypoglycemia; Levofloxacin; Male; Medical Records; Middle Aged; Multivariate Analysis; Ofloxacin; Prevalence; Retrospective Studies; Rhode Island; Risk Factors