Download Pleiotropic Effects of Antimicrobial Agents

SAMFORD UNIVERSITY GLOBAL DRUG INFORMATION SERVICE’S
C L I PS
CURRENT LITERATURE AND INFORMATION FOR PHARMACISTS®
http://www.samford.edu/pharmacy/drug-information-center/
Volume 19 (Issue 5)
February 9, 2015
PLEIOTROPIC EFFECTS OF ANTIMICROBIAL AGENTS
Although unintended effects of antimicrobial agents occur, some effects may produce therapeutic advantages. Many
anti-infective agents have effects that stem beyond their anti-infectiveness. These advantages include anti-inflammatory
and immunomodulatory properties. The other therapeutic advantages of antibacterial agents are not approved for use
by the (Food and Drug Administration) FDA. However, the risk:benefit profile for using these agents must clearly be
defined. A critical review of the beneficial non-antiinfective effects of antimicrobial agents (e.g., macrolides, tetracyclines,
sulfonamides, and ketoconazole) was evaluated. If you need further information, please contact the Samford University
Drug Information Service at (205) 726-2659.
Sadarangani SP, Estes LL, Steckelberg JM. Non-anti-infective effects of antimicrobials and their clinical applications:
a review: Mayo Clin Proc. 2015;90(1):109-127.
Methods
 Comprehensive PubMed search between January 1, 2000 and April 25, 2014 was conducted.
 Bibliographic searches were also used in data analysis.
Results
Table 1: Non-antiinfective effects of antimicrobial agents
DRUG / CLASS
MECHANISM OF
ADVERSE EFFECTS
PLEIOTROPIC EFFECTS
ACCEPTED USE
ACTION
(LONG-TERM USE)
Cystic Fibrosis-may reduce
Macrolides
Bacteriostatic
Long term use:
Anti-inflammatory,
polyketide
Nausea, vomiting,
immunomodulatory
exacerbations; may be used in
patients with Pseudomonas
abdominal pain, drug- effects; inhibit
aeruginosa (azithromycin dose:
drug interactions; QTc proinflammatory
prolongation,
cytokines, decrease
500 mg three twice a week [or
resistance
mucus
daily] in patients who weighed at
hypersecretion
least 40 kg, and 250 mg three
times a week [or daily] for
patients who weighed less than
40 kg.
Non-CF bronchiectasis- may
reduce exacerbations
BOS-death benefit if
azithromycin used in stage I
BOS
Diffuse panbronchiolitis-low dose
erythromycin (improved survival
rate / pulmonary function),
erythromycin 400-600 mg/day;
clarithromycin 200 mg/day.
COPD-may reduce
exacerbations in patients with
moderate COPD (azithromycin
500 mg three times a week for
12 months)
Endoscopy in UGIBerythromycin improved
visualization and reduced need
for repeated endoscopy
CONTINUED NEXT PAGE
Table 1: Non-antiinfective effects of antimicrobial agents (continued)
MECHANISM OF
ADVERSE EFFECTS
PLEIOTROPIC EFFECTS
ACCEPTED USE
ACTION
(LONG-TERM USE)
Acne vulgaris-improvement in
Tetracyclines
Antioxidant
Nausea, anorexia,
Anti-inflammatory,
properties through
diarrhea,
immunomodulatory,
inflammatory lesions
free radical
photosensitivity,
and antiapoptotic
(doxycycline 40-100 mg/day)
Rosacea-possible benefit
scavenging;
hepatotoxicity, tooth
properties.
protects cells from
discoloration,
Increased sebum
(doxycycline 40 mg/day)
Ocular rosacea-some
apoptosis, affects
cutaneous
production, altered
caspase-dependent hyperpigmentation
keratinization,
improvement in blepharitis
apoptotic pathway,
(minocycline), drugrelease of
(oxytetracycline 250 mg twice
inhibit
drug interactions
inflammatory
daily)
Periodontitis-reduced severity of
endopeptidases
mediators,
Propionobacterium
periodontal disease + traditional
acnes follicular
therapy (minocycline 100-200
colonization
mg/day X 7-14 days)
RA-may reduce disease severity
and joint swelling
Granulomatosis with polyangiitisSulfonamides
Anti-inflammatory
Gastrointestinal
Anti-inflammatory
(Trimethoprim effects interfere with adverse effects,
effects
insufficient evidence
sulfamethoxazole) oxygen-derived free hepatic toxicity,
radicals
myelosuppression,
renal impairment,
hyperkalemia,
contraindication with
patients with glucose6-phosphate
dehydrogenase
deficiency
Advanced prostate cancer- may
Ketoconazole
Imidazole
Nausea, vomiting,
Antiandrogen effects
derivative; inhibits
diarrhea,
help to achieve stable disease or
CYP450 14aphotophobia,
clinical response in patients with
demthylase(catalysi thrombocytopenia,
hormone refractory prostate
s conversion of
oligospermia,
cancer (ketoconazole 1200
lanosterol to
impotence; drug-drug
mg/day)
cholesterol)
interactions
BOS-Bronchiolitis obliterans syndrome; UGIB-Upper GI Bleeding; RA-rheumatoid arthritis
DRUG / CLASS
Conclusions
 Most antimicrobial agents have multiple effects, some of which, can be therapeutically beneficial.
 Many of the ways in which these antimicrobials are used are not FDA approved.
 Dosages for unapproved uses are largely unknown.
 The recommendation to use these agents will be dependent upon an acceptable risk:benefit profile that
minimizes adverse events and toxicities.
2
Prepared by: Maisha Kelly Freeman, PharmD, MS, BCPS, FASCP
Pleiotropic effects of antimicrobial agents. CLIPs- Current Literature and Information for Pharmacists. 2015 Feb 9;19(5)1-2.