Non-anti-infective effects of antimicrobials and their clinical applications: a review.

Antimicrobial agents are undoubtedly one of the key advances in the history of modern medicine and infectious diseases, improving the clinical outcomes of infection owing to their inhibitory effects on microbial growth. However, many antimicrobial agents also have biological activities stemming from their interactions with host receptors and effects on host inflammatory responses and other human or bacterial cellular biological pathways. These result in clinical uses of antimicrobial drugs that are distinct from their direct bacteriostatic or bactericidal properties. We reviewed the published literature regarding non-anti-infective therapeutic properties and proposed clinical applications of selected antimicrobials, specifically, macrolides, tetracyclines, sulfonamides, and ketoconazole. The clinical applications reviewed were varied, and we focused on uses that were clinically relevant (in terms of importance and burden of disease) and where published evidence exists. Such uses include chronic inflammatory pulmonary and skin disorders, chronic periodontitis, gastrointestinal dysmotility, rheumatoid arthritis, and cancer. Most of these potential therapeutic uses are not Food and Drug Administration approved. Clinicians need to weigh the use of antimicrobial agents for their non-anti-infective benefits, considering potential adverse effects and long-term effect on microbial resistance.

Effect of combined fluoroquinolone and azole use on QT prolongation in hematology patients.

QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (P = 0.03) and a left-ventricular ejection fraction of <55% (P = 0.02). Low magnesium (P = 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (P = 0.17), and female sex (P = 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP.

Characterization of bacterial infections in allogeneic hematopoietic stem cell transplant recipients who received prophylactic levofloxacin with either penicillin or doxycycline.

OBJECTIVE: To describe the effect of a combination prophylactic regimen of levofloxacin, a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class, with either penicillin or doxycycline on the changing epidemiology of bacterial infections and antimicrobial resistance patterns of isolated organisms in the allogeneic hematopoietic stem cell transplant (HSCT) patient population. PATIENTS AND METHODS: We conducted a single-center, retrospective cohort study of all allogeneic HSCT recipients from January 1, 2003, through August 31, 2008, who received prophylactic levofloxacin in combination with penicillin (or with doxycycline in penicillin-allergic patients) from allogeneic stem cell infusion until neutrophil engraftment. RESULTS: Of the 258 patients who underwent allogeneic HSCT during the study period, 231 received levofloxacin prophylaxis, 76 (33%) of whom developed an infection within 3 months after transplant. Over time, the ratio of gram-positive to gram-negative (GN) infections decreased from 2.11 in 2004, the first year that GN organisms were isolated, to 1.11 in 2008 (P=.20). Emergence of fluoroquinolone-resistant GN bacteria was observed (P=.02), whereas resistance to extended-spectrum beta-lactams did not change over time. Combined vancomycin-resistant enterococci colonization and infection rates increased during the study period (P=.04). Clostridium difficile colitis was uncommon. CONCLUSION: Levofloxacin with penicillin or doxycycline prophylaxis may contribute to the emergence of resistant GN infections in allogeneic HSCT recipients over time. Our findings provide additional support for the current standard of practice of administering empiric monotherapy with an antipseudomonal beta-lactam if these patients develop fever or are suspected to have an infection.