VA Class: DE101
Chemical Name: 2-Methyl-5-nitro-1H-imidazole-1-ethanol
Molecular Formula: C6H9N3O3
CAS Number: 443-48-1
Brands: MetroCream, MetroGel, MetroGel-Vaginal, MetroLotion, Noritate, Vandazole
Uses for Metronidazole
Treatment of inflammatory lesions (papules and pustules) associated with rosacea (acne rosacea);1 2 8 9 10 16 17 18 19 20 21 47 180 184 207 topical gel designated an orphan drug by FDA for use in this condition.23
Optimal treatment not determined; inflammatory lesions may respond to long-term treatment with topical anti-infectives (e.g., metronidazole) or oral anti-infectives (e.g., doxycycline, tetracycline, erythromycin, ampicillin, metronidazole).10 11 12 13 15 16 17 20 21 47 80 82 2 8 9 10 16 17 18 19 20 21 47 80 81 82 Topical metronidazole may be preferred to oral metronidazole;17 147 has been effective in patients with inadequate response or relapse with other therapies (e.g., oral tetracycline).2 10 17 21 62
Treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, anaerobic vaginosis)109 111 112 114 115 119 120 122 123 139 153 183 214 in nonpregnant women.214
CDC recommends treatment of bacterial vaginosis in all symptomatic women (including pregnant women).109 In addition, asymptomatic pregnant women at high risk for complications of pregnancy should be screened (preferably at the first prenatal visit) and treatment initiated if needed.109
Treatment recommendations for bacterial vaginosis in HIV-infected women are the same as those for women without HIV infection.109
Regimens of choice in nonpregnant women are a 7-day regimen of oral metronidazole, a 5-day regimen of intravaginal metronidazole gel, or a 7-day regimen of intravaginal clindamycin cream;109 114 alternative regimens are a 7-day regimen of oral clindamycin or 3-day regimen of intravaginal clindamycin suppositories.109 114 The preferred regimens for pregnant women are a 7-day regimen of oral metronidazole or a 7-day regimen of oral clindamycin.109
Regardless of regimen used, relapse or recurrence is common;109 110 120 122 138 153 162 an alternative regimen (e.g., oral therapy when topical was used initially) may be used in such situations.109 122
Decubitus and Other Ulcers
Has been used intravaginally as an adjunct to oral metronidazole for treatment of trichomoniasis caused by Trichomonas vaginalis† in selected cases (e.g., refractory infections),156 205 but not included in CDC recommendations for treatment of trichomoniasis.109 Intravaginal metronidazole not effective used alone.114
Metronidazole Dosage and Administration
Prior to topical application, wash affected area with mild, nonirritating cleanser.1 2 180 184 207 To minimize risk of local irritation, some clinicians suggest application be delayed until about 15–20 minutes after skin cleansing.99
Intravaginal Topical Administration
If once-daily regimen used, use new vaginal applicator for each dose.214 If twice-daily regimen used, use new applicator each day; wash, rinse, and dry applicator after morning dose and discard after evening dose.214
Treatment in Nonpregnant Postmenarchal FemalesIntravaginal
0.75% gel: One applicatorful (approximately 37.5 g of metronidazole) once daily (at bedtime) or twice daily (in morning and evening) given for 5 consecutive days.214
Treatment in Nonpregnant WomenIntravaginal
Cautions for Metronidazole
Seizures and Peripheral Neuropathy
Psychotic reactions reported in alcoholic patients receiving oral metronidazole and disulfiram concurrently;183 214 disulfiram-like reactions to alcohol reported in patients receiving oral metronidazole.106 183 214 Similar reactions could occur with intravaginal metronidazole.183 214
Avoid intravaginal metronidazole in patients who have received disulfiram within the last 2 weeks.183 214 Caution patients to avoid drinking alcohol while being treated with intravaginal metronidazole.183 214 (See Specific Drugs under Interactions.)
History of Blood Dyscrasia
Vaginal Intercourse and Use of Vaginal Products
Patients treated with vaginal gel should not engage in vaginal intercourse111 112 113 183 214 and should not use other vaginal products (tampons, douches) during entire treatment course.111 112 113 214
Vaginal intercourse or other vaginal products could reduce efficacy of intravaginal metronidazole (e.g., by dislodgment and/or dilution, by increased vaginal pH secondary to deposition of semen).111 112 113 214
Symptoms of known or previously unrecognized vaginal candidiasis may become more prominent during intravaginal metronidazole therapy.183 214 Symptomatic Candida vaginitis reported during or immediately after therapy.183 214
Systemic Adverse Effects
Although topical application to skin results in lower systemic absorption than oral or IV administration, adverse systemic effects (e.g., metallic taste,1 180 207 nausea,1 180 207 paresthesia,184 tingling or numbness of extremities1 180 207 ) have been reported with topical metronidazole.1 180
Although intravaginal administration results in lower systemic absorption than oral or IV administration, consider possibility that adverse effects reported with systemic metronidazole could occur when drug is given intravaginally.115 119 183 214
Safety and efficacy of intravaginal metronidazole for treatment of bacterial vaginosis in pregnant women not established.109 119 183 214 Existing data do not support use of intravaginal agents during pregnancy and intravaginal metronidazole not included in current CDC recommendations for treatment of bacterial vaginosis in pregnant women.109
One manufacturer states safety and efficacy of vaginal gel established in postmenarchal females based on extrapolation of data from adult women; safety and efficacy of vaginal gel not established in premenarchal females.214
Safety and efficacy of topical gel in geriatric patients ≥65 years of age appear similar to those in younger adults.1
Insufficient experience with vaginal gel in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.214
Common Adverse Effects
Intravaginal administration: Vaginal discharge,183 symptomatic Candida cervicitis/vaginitis,183 fungal infection,214 vulvovaginal irritation,183 dysmenorrhea,214 GI effects (abdominal pain, GI discomfort, nausea, vomiting, diarrhea),183 214 headache,183 214 pruritus.214
Interactions for Metronidazole
Because metronidazole can be absorbed systemically following topical application to skin1 2 9 10 21 47 207 or following intravaginal administration,119 131 132 183 214 the possibility that drug and laboratory test interactions could occur with these routes should be considered.106 183 f
Specific Drugs and Laboratory Tests
Disulfiram-like reactions reported rarely when alcohol ingested during intravaginal metronidazole treatment;106 183 214 such reactions not reported to date with topical application of metronidazole to skin21 47 61 99
Anticoagulants, oral (warfarin)
Consider possibility of increased metronidazole adverse effects182
Tests based on ultraviolet (UV) absorbance
Falsely decreased serum concentrations (including undetectable concentrations) of AST, ALT, LDH, triglycerides, or hexokinase glucose may be reported during metronidazole therapy if results are based on decreases in UV absorbance that occur during oxidation-reduction of NADH/NAD30 183 214
Following repeated topical application to the face of 1% cream (approximately 3.75 mg per dose) in adults with rosacea, serum concentrations were minimal or undetectable.9 Following topical application to the face of 1 g of 1% cream in healthy individuals, serum concentrations were minimal or undetectable and peak serum concentrations were attained within 8–12 hours after the dose.184
Following topical application to the face of 1 g of 1% topical gel in adults with rosacea, peak serum concentrations of metronidazole were attained 6–10 hours after the dose and were <1% of concentrations reported with a single 250-mg oral dose.1
Following topical application to the face of 1 g of 0.75% topical lotion (approximately 7.5 mg of metronidazole) twice daily for 4 days, drug was detectable in plasma of all patients and peak plasma concentrations were approximately 80 times lower than peak concentrations attained with a single 250-mg oral dose.207
Following intravaginal administration of 5 g of 0.75% vaginal gel (approximately 37.5 mg of metronidazole) in healthy women, peak serum concentrations were attained 4–17 hours after the dose and were approximately 2% of that attained after a single 500-mg oral dose.119 132 183 186 214
Distributed into milk following oral or IV administration;1 30 45 56 131 180 183 184 207 214 not known whether distributed into milk following topical application to skin1 or intravaginal administration.183
20–25°C (may be exposed to 15–30°C).1
20–25°C; do not freeze.207
MetroGel-Vaginal: 15–30°C; do not freeze.183
Vandazole: 20–25°C; do not freeze.214
Un-ionized at physiologic pH49 and readily taken up by anaerobic organisms or cells.48 49 50 56 72 In susceptible organisms or cells, metronidazole reduced by low-redox-potential electron transport proteins (e.g., nitroreductases such as ferredoxin);48 49 50 56 64 65 66 68 69 70 71 72 the reduction product(s) apparently are responsible for cytotoxic and antimicrobial effects of the drug (e.g., disruption of DNA, inhibition of nucleic acid synthesis).48 56 63 64 65 66 67 68 70 71 72
Mechanism of reducing inflammatory lesions (papules and pustules) and erythema in patients with rosacea not elucidated to date;1 2 6 10 11 17 19 21 28 29 184 207 these effects may result from anti-inflammatory or immunosuppressive actions of the drug.1 2 3 10 17 28 29 207
Suppression of skin bacteria does not appear to play a major role in the mechanism of action of the drug in treatment of inflammatory lesions of rosacea;2 10 11 29 inactive in vitro against Propionibacterium acnes,2 4 5 48 staphylococci, and streptococci,2 48 and has no appreciable effects on the aerobic or anaerobic microflora of the skin of patients with rosacea.2 10 29
Spectrum of activity includes most obligately anaerobic bacteria2 7 29 30 45 48 53 56 64 and many protozoa.2 29 30 48 52 64 Inactive against fungi2 3 48 and viruses48 and most aerobic or facultatively anaerobic bacteria.2 7 30 45 48 73 74
Gram-positive anaerobes: Active against Clostridium,2 30 45 48 53 55 C. difficile,54 55 C. perfringens,48 55 Eubacterium,2 30 45 48 53 54 Peptococcus,2 30 45 48 53 54 55 and Peptostreptococcus.2 7 30 45 48 53 55 124 128 Actinomyces, Lactobacillus,48 Propionibacterium acnes,2 4 5 48 P. avidum,5 and P. granulosum5 generally are resistant.
Gram-negative anaerobes: Active against Bacteroides fragilis,2 3 30 45 48 53 54 55 124 126 130 B. distasonis,30 45 54 55 124 B. ovatus,30 45 55 124 B. thetaiotaomicron,30 45 54 55 124 B. vulgatus,30 45 54 55 124 B. ureolyticus,124 126 Fusobacterium,2 7 30 45 48 53 55 Prevotella bivia,53 124 126 128 129 P. disiens,54 128 P. intermedia,7 124 P. melaninogenica,48 54 124 126 128 129 P. oralis,54 124 126 129 Porphyromonas,124 129 and Veillonella.7 54 55
Other organisms: Active against Campylobacter fetus.48 Most strains of Gardnerella vaginalis (formerly Haemophilus vaginalis) are susceptible only to relatively high concentrations in vitro.119 126 129 135 140 141 142 Concentrations readily achievable locally (750 mcg/mL) following intravaginal application of 0.75% vaginal gel have inhibited approximately 90% of strains tested in vitro.119 177
Natural and acquired resistance has been reported in some T. vaginalis.48 52 75 76 77 78 79 Resistance also reported rarely in B. fragilis and other anaerobic bacteria following long-term therapy.44 48 215
Advice to Patients
Advise patients that vaginal gel is for intravaginal administration only and to avoid contact with eyes.183 214 (See Administration under Dosage and Administration.) If such contact occurs, importance of irrigating eyes with copious amounts of cool water.177 183
Instruct patients receiving vaginal gel regarding appropriate use of vaginal applicator.f
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
MetroCream (with benzyl alcohol)
Noritate (with parabens)
MetroGel (with parabens and propylene glycol)
MetroGel-Vaginal (with parabens and propylene glycol; with vaginal applicators)
Vandazole (with parabens and propylene glycol; with vaginal applicators)
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
MetroCream 0.75% Cream (GALDERMA): 45/$356.39 or 135/$1,052.94
Metrogel 1% Gel (GALDERMA): 60/$220.00 or 180/$625.98
Metrogel 1% Kit (GALDERMA): 1/$205.99 or 3/$592.99
MetroGel-Vaginal 0.75% Gel (GRACEWAY PHARMACEUTICALS): 70/$45.99 or 140/$79.97
MetroLotion 0.75% Lotion (GALDERMA): 59/$362.58 or 177/$1,037.93
MetroNIDAZOLE 0.75% Cream (FOUGERA): 45/$175.98 or 135/$505.99
MetroNIDAZOLE 0.75% Gel (FOUGERA): 45/$163.99 or 135/$471.98
MetroNIDAZOLE 0.75% Gel (SANDOZ): 70/$59.99 or 210/$174.96
MetroNIDAZOLE 0.75% Lotion (FOUGERA): 59/$240.00 or 177/$689.96
Noritate 1% Cream (DERMIK): 60/$175.99 or 180/$509.98
Vandazole 0.75% Gel (UPSHER-SMITH): 70/$46.99 or 140/$81.98
AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Galderma. MetroGel (metronidazole) 1% topical gel prescribing information. Fort Worth, TX; 2005 Jul.
2. Curatek Pharmaceuticals. MetroGel (metronidazole) 0.75% topical gel product monograph. Elk Grove Village, IL; 1988 Nov.
3. Gamborg Nielsen P. In vitro antifungal effect of metronidazole on Pityrosporum ovale. Mykosen. 1984; 27:475-6. [PubMed 6504071]
4. Denys GA, Jerris RC, Swenson JM et al. Susceptibility of Propionibacterium acnes clinical isolates to 22 antimicrobial agents. Antimicrob Agents Chemother. 1983; 23:335-7. [IDIS 166100] [PubMed 6838191]
5. Hoffler U, Niederau W, Pulverer G. Susceptibility of cutaneous Propionibacteria to newer antibiotics. Chemotherapy. 1980; 26:7-11. [IDIS 113266] [PubMed 7353441]
6. Persi A, Rebora A. Metronidazole and Demodex folliculorum. Acta Derm Venereol. 1981; 61:182-3. [PubMed 6165206]
7. Wade WG, Addy M. Comparison of in vitro activity of niridazole, metronidazole and tetracycline against subgingival bacteria in chronic periodontitis. J Appl Bacteriol. 1987; 63:455-7. [PubMed 3440767]
8. Dupont C. Metronidazole suspension applied topically for rosacea. Br J Dermatol. 1984; 111:499-502. [IDIS 193515] [PubMed 6237665]
9. Gamborg Nielsen P. Treatment of rosacea with 1% metronidazole cream: a double-blind study. Br J Dermatol. 1983; 108:327-32. [IDIS 168048] [PubMed 6219689]
10. Gamborg Nielsen P. Metronidazole treatment of rosacea. Int J Dermatol. 1988; 27:1-5. [PubMed 2964423]
11. Pye RJ, Burton JL. Treatment of rosacea by metronidazole. Lancet. 1976; 1:1211-2. [PubMed 58258]
12. Wilkin JK. Rosacea. Int J Dermatol. 1983; 22:393-400. [PubMed 6226618]
13. Kurkcuoglu N, Atakan N. Metronidazole in the treatment of rosacea. Arch Dermatol. 1984; 120:837. [IDIS 187231] [PubMed 6233939]
14. Tanga MR, Antani JA, Kabade SS. Clinical evaluation of metronidazole as an anti-inflammatory agent. Int Surg. 1975; 60:75-6. [PubMed 1090554]
15. Saihan EM, Burton JL. A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Br J Dermatol. 1980; 102:443-5. [IDIS 113211] [PubMed 6446314]
16. Veien NK, Christiansen JV, Hjorth N et al. Topical metronidazole in the treatment of rosacea. Cutis. 1986; 38:209-10. [PubMed 2945705]
17. Bleicher PA, Charles JH, Sober AJ. Topical metronidazole therapy for rosacea. Arch Dermatol. 1987; 123:609-14. [IDIS 228765] [PubMed 2953312]
18. Gamborg Nielsen P. The relapse rate for rosacea after treatment with either oral tetracycline or metronidazole cream. Br J Dermatol. 1983; 109:122.
19. Hirschmann JV. Topical antibiotics in dermatology. Arch Dermatol. 1988; 124:1691-1700. [IDIS 248352] [PubMed 2972259]
20. Gamborg Nielsen P. A double-blind study of 1% metronidazole cream versus systemic oxytetracycline therapy for rosacea. Br J Dermatol. 1983; 109:63-5. [IDIS 173452] [PubMed 6222756]
21. Aronson IK, Rumsfield JA, West DP et al. Evaluation of topical metronidazole gel in acne rosacea. Drug Intell Clin Pharm. 1987; 21:346-51. [IDIS 228575] [PubMed 2952478]
22. Persi A, Rebora A. Metronidazole in the treatment of rosacea. Arch Dermatol. 1985; 121:307-8. [PubMed 3156561]
23. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by Orphan Drug Act (P.L. 97-414). Rockville, MD; Jun 15, 2001. From FDA web site (http: / / www.fda.gov / ForIndustry / DevelopingProductsforRareDiseasesConditions / HowtoapplyforOrphanProductDesignation / default.htm).
24. Wotton PK, Mollgaard B, Hadgraft J et al. Vehicle effect on topical drug delivery: III. Effect of azone on the cutaneous permeation of metronidazole and propylene glycol. Int J Pharm. 1985; 24:19-26.
25. Mollgaard B, Hoelgaard A. Vehicle effect on topical drug delivery: II. Concurrent skin transport of drugs and vehicle components. Acta Pharm Suec. 1983; 20:443-50. [PubMed 6675423]
26. Hoelgaard A, Mollgaard B, Baker E. Vehicle effect on topical drug delivery: IV. Effect of N-methylpyrrolidone and polar lipids on percutaneous drug transport. Int J Pharm. 1988; 43:233-40.
27. Hughes J, Tenni P, McDonald C et al. Solubility of metronidazole for topical application. Aust J Hosp Pharm. 1982; 12:58.
28. Miyachi Y, Imamura S, Niwa Y. Anti-oxidant action of metronidazole: a possible mechanism of action in rosacea. Br J Dermatol. 1986; 114:231-4. [PubMed 2936372]
29. Eriksson G, Nord CE. Impact of topical metronidazole on the skin and colon microflora in patients with rosacea. Infection. 1987; 15:8-10. [PubMed 2952597]
30. G.D. Searle & Co. Flagyl (metronidazole) prescribing information. Chicago, IL; 1997 Apr 16.
31. Esterly NB, Furey NL, Flanagan LE. The effect of antimicrobial agents on leukocyte chemotaxis. J Invest Dermatol. 1978; 70:51-5. [PubMed 618981]
32. Bahr V, Ullmann U. The influence of metronidazole and its two main metabolites on murine in vitro lymphocyte transformation. Eur J Clin Microbiol. 1983; 2:568-70. [PubMed 6667682]
33. Gnarpe H, Persson S, Belsheim J. Influence of metronidazole and tinidazole on leukocyte chemotaxis in Crohn’s disease. Infection. 1978; 6(Suppl 1):S107-9.
34. Gnarpe H, Belsheim J, Persson S. Influence of nitroimidazole derivatives on leukocyte migration. Scand J Infect Dis. 1981; 26:68-71.
35. Grove DI, Mahmoud AA, Warren KS. Suppression of cell-mediated immunity by metronidazole. Int Arch Allergy Appl Immunol. 1977; 54:422-7. [PubMed 328408]
36. Mitchell L. Topical metronidazole in the treatment of dry socket. Br Dent J. 1984; 156:132-4. [PubMed 6367781]
37. Mitchell L. Topical metronidazole in the treatment of dry socket. Br Dent J. 1984; 156:348. [PubMed 6587867]
38. Stamper EB. Topical metronidazole in the treatment of dry socket. Br Dent J. 1984; 156:348-9. [PubMed 6587867]
39. Gomolin IH, Brandt JL. Topical metronidazole therapy for pressure sores of geriatric patients. J Am Geriatr Soc. 1983; 31:710-2. [IDIS 178665] [PubMed 6630831]
40. Pierleoni EE. Topical metronidazole therapy for infected decubitus ulcers. J Am Geriatr Soc. 1984; 32:775. [IDIS 191331] [PubMed 6481058]
41. Mioduch HJ. Topical metronidazole for pressure sores. Hosp Pharm. 1985; 20:863.
42. Jones PH. Treatment of anaerobically infected pressure sores with topical metronidazole. Lancet. 1978; 1:214.
43. Khanna AK, Khanna A, Asthana AK. Postirradiation ulcer and topical metronidazole. Cancer Invest. 1988; 6:123-4. [PubMed 3365569]
44. Ingham HR, Eaton S, Venables CW et al. Bacteroides fragilis resistant to metronidazole after long-term therapy. Lancet. 1978; 1:214. [PubMed 74641]
45. SCS Pharmaceuticals. Flagyl IV (metronidazole hydrochloride) for IV infusion only prescribing information (dated 1999 Jul 23). In: Physicians’ desk reference. 55th ed. Montvale, NJ: Medical Economics Company Inc; 2001:2967-9.
46. Moesgaard F, Nielsen ML. Failure of topically applied antibiotics, added to systemic prophylaxis, to reduce perineal wound infection in abdominal perineal excision of the rectum. Acta Chir Scand. 1988; 154:589-92. [PubMed 3063043]
47. Anon. Topical metronidazole for rosacea. Med Lett Drugs Ther. 1989; 31:75-6. [PubMed 2526918]
48. Lorian V, ed. Antibiotics in laboratory medicine. 2nd ed. Baltimore, MD: Williams $0 Wilkins; 1986:285-93.
49. Muller M, Lindmark DG, McLaughlin J. Mode of action of metronidazole on anaerobic microorganisms. In: Finegold S, ed. Metronidazole. Princeton, NJ: Excerpta Medica; 1977:12-9.
50. Brogden RN, Heel RC, Speight TM et al. Metronidazole in anaerobic infections: a review of its activity, pharmacokinetics and therapeutic use. Drugs. 1978; 16:387-417. [IDIS 118924] [PubMed 363399]
51. Phillips TL. Chemical modification of radiation effects. Cancer. 1977; 39:987-98. [IDIS 82665] [PubMed 319901]
52. Sears SD, O’Hare J. In vitro susceptibility of Trichomonas vaginalis to 50 antimicrobial agents. Antimicrob Agents Chemother. 1988; 32:144-6. [IDIS 243879] [PubMed 3258142]
53. Heard ML, Bawdon RE, Hemsell DL et al. Susceptibility profiles of potential aerobic and anaerobic pathogens isolated from hysterectomy patients. Am J Obstet Gynecol. 1984; 149:133-43. [IDIS 185398] [PubMed 6562855]
54. Rolfe RD, Finegold SM. Comparative in vitro activity of new beta-lactam antibiotics against anaerobic bacteria. Antimicrob Agents Chemother. 1981; 20:600-9. [IDIS 141473] [PubMed 7325628]
55. Kesado T, Watanabe K, Asahi Y et al. Susceptibilities of anaerobic bacteria to N-formimidoyl thienamycin (MK0787) and to other antibiotics. Antimicrob Agents Chemother. 1982; 21:1016-22. [IDIS 151730] [PubMed 6956247]
56. Shank WA Jr, Amerson AB. Metronidazole: an update of its expanding role in clinical medicine. Hosp Formul. 1981; 16:283-97.
57. Beard CM, Kenneth MP, Noller L et al. Lack of evidence for cancer due to use of metronidazole. N Engl J Med. 1979; 301:519-22. [PubMed 460304]
58. Friedman GD. Cancer after metronidazole. N Engl J Med. 1980; 302:519-20. [IDIS 110409] [PubMed 7351980]
59. Noyan U, Yilmaz S, Kuru B et al. A clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients. J Clin Periodontol. 1997; 24:158-65. [PubMed 9083899]
60. The United States pharmacopeia, 22nd rev, and the national formulary, 17th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1990:1831.
61. Borgman R (Curatek Pharmaceutical, Elk Grove Village, IL): Personal communication; 1989 Oct 13.
62. Lowe NJ, Henderson T, Millikan LE et al. Topical metronidazole for severe and recalcitrant rosacea: a prospective open trial. Cutis. 1989; 43:283-6. [PubMed 2523290]
63. LaRusso NF, Tomasz M, Müller M et al. Interaction of metronidazole with nucleic acids in vitro. Mol Pharmacol. 1977; 13:872-82. [PubMed 895722]
64. Müller M. Mode of action of metronidazole on anaerobic bacteria and protozoa. Surgery. 1983; 93(1 Part 2):165-71. [PubMed 6849201]
65. Müller M. Reductive activation of nitroimidazoles in anaerobic microorganisms. Biochem Pharmacol. 1986; 35:37-41. [PubMed 3940525]
66. Knight RC, Skolimowski IM, Edwards DI. The interaction of reduced metronidazole with DNA. Biochem Pharmacol. 1978; 27:2089-93. [PubMed 569481]
67. Edwards DI. The action of metronidazole on DNA. J Antimicrob Chemother. 1977; 3:43-8. [PubMed 557472]
68. Edwards DI. Mechanism of antimicrobial action of metronidazole. J Antimicrob Chemother. 1979; 5:499-502. [PubMed 387703]
69. Knox RJ, Knight RC, Edwards DI. Studies on the action of nitroimidazole drugs: the products of nitroimidazole reduction. Biochem Pharmacol. 1983; 32:2149-56. [PubMed 6870942]
70. Edwards DI. Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs. Br J Vener Dis. 1980; 56:285-90. [PubMed 7000306]
71. Lindmark DG, Müller M. Antitrichomonad action, mutagenicity, and reduction of metronidazole and other nitroimidazoles. Antimicrob Agents Chemother. 1976; 10:476-82. [PubMed 791102]
72. Müller M, Lindmark DG. Uptake of metronidazole and its effect on viability in trichomonads and Entamoeba invadens under anaerobic and aerobic conditions. Antimicrob Agents Chemother. 1976; 9: 696-700. [PubMed 1083712]
73. Edwards DI, Shanson D. Metronidazole inactivation by aerobes. J Antimicrob Chemother. 1980; 6:402-3. [PubMed 6995421]
74. Edwards DI, Thompson EJ, Tomusange J et al. Inactivation of metronidazole by aerobic organisms. J Antimicrob Chemother. 1979; 5:315-6. [PubMed 113378]
75. Müller M, Lossick JG, Gorrell TE. In vitro susceptibility of Trichomonas vaginalis to metronidazole and treatment outcome in vaginal trichomoniasis. Sex Transm Dis. 1988; 15:17-24. [PubMed 3258675]
76. Müller M, Meingassner JG, Miller WA et al. Three metronidazole-resistant strains of Trichomonas vaginalis from the United States. Am J Obstet Gynecol. 1980; 138:808-12. [IDIS 126829] [PubMed 7004190]
77. Lossick JG, Müller M, Gorrell TE. In vitro drug susceptibility and doses of metronidazole required for cure in cases of refractory vaginal trichomoniasis. J Infect Dis. 1986; 153:948-55. [IDIS 320849] [PubMed 3486237]
78. Lossick JG. Treatment of Trichomonas vaginalis infections. Rev Infect Dis. 1982; 4(Suppl):S801-18.
79. Müller M, Gorrell TE. Metabolism and metronidazole uptake in Trichomonas vaginalis isolates with different metronidazole susceptibilities. Antimicrob Agents Chemother. 1983; 24:667-73. [PubMed 6607028]
80. Fitzpatrick TB, Eisen AZ, Wolff K et al, eds. Dermatology in general medicine: textbook and atlas. 3rd ed. New York: McGraw Hill Book Company; 1987: 679-85.
81. Goldsmith MF. New topical therapy for acne rosacea offers conspicuous improvement, no systemic effects. JAMA. 1989; 261:2014-5. [PubMed 2522563]
82. Grosshans E. [Rosacea.] (French; with English abstract.) Presse Med. 1988; 17:2393-8.
83. Browning DJ, Proia AD. Ocular rosacea. Surv Ophthalmol. 1986; 31:145-58. [PubMed 2433782]
84. Schell H, Vogt HJ, Mack-Hennes A. [Treatment of rosacea with isotretinoin: results of a multicenter trial follow-up.] Z Hautkr. 1987; 62:1129-33.
85. Turjanmaa K, Reunala T. Isotretinoin treatment of rosacea. Acta Derm Venereol. 1987; 67:89-91. [PubMed 2436425]
86. Hoting E, Paul E, Plewig G. Treatment of rosacea with isotretinoin. Int J Dermatol. 1986; 25:660-3. [PubMed 2948928]
87. Plewig G, Braun-Falco O, Klövekorn W et al. [Isotretinoin in local treatment of acne and rosacea and animal experiment studies on isotretinoin and arotinoid]. Hautarzt. 1986; 37:138-41. [PubMed 2939041]
88. Mahrle G, Bauermeister-Jasso K, Enderer K. [Roaccutan in acne and rosacea.] Z Hautkr. 1985; 60:120,125-34.
89. Plewig G, Nikolowski J, Wolff HH. Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol. 1982; 6(4 Part 2):766-85. [PubMed 6461680]
90. Nikolowski J, Plewig G. [Oral treatment of rosacea with 13-cis-retinoic acid.] Hautarzt. 1981; 32:575-84.
91. Nunzi E, Rebora A, Hamerlinck F et al. Immunopathological studies on rosacea. Br J Dermatol. 1980; 103:543-51. [PubMed 6449213]
92. Metronidazole (Flagyl) interactions. In: Hansten PD, Horn JR. Drug interactions & updates. Vancouver, WA: Applied Therapeutics; 1993(Jul):239-42.
93. Anticoagulants, oral/metronidazole. In: Tatro DS, Olin BR, Hebel SK, eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(Jan):82.
94. O’Reilly RA. The stereoselective interaction of warfarin and metronidazole in man. N Engl J Med. 1976; 295:354. [PubMed 934223]
95. Kazmier FJ. A significant interaction between metronidazole and warfarin. Mayo Clin Proc. 1976; 51:782. [PubMed 994556]
96. Dean RP, Talbert RL. Bleeding associated with concurrent warfarin and metronidazole therapy. Drug Intell Clin Pharm. 1980; 14:864-6.
97. Disulfiram/metronidazole. In: Tatro DS, Olin BR, Hebel SK, eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(Jan):304.
98. Ethanol/metronidazole. In: Tatro DS, Olin BR, Hebel SK, eds. Drug interaction facts. St. Louis: JB Lippincott Co; 1990(Jan):335.
99. Reviewers’ comments (personal observations); 1989 Oct.
100. Herman J. Metronidazole for a malodorous pressure sore. Practitioner. 1983; 227:1595-6. [IDIS 178217] [PubMed 6634628]
101. Baker PG, Haig G. Metronidazole in the treatment of chronic pressure sores and ulcers: a comparison with standard treatments in general practice. Practitioner. 1981; 225:569-73. [IDIS 164758] [PubMed 7024971]
102. Ashford RFU, Plant GT, Maher J et al. Metronidazole in smelly tumours. Lancet. 1980; 1: 874-5. [IDIS 111983] [PubMed 6103225]
103. Doll DC, Doll KJ. Malodorous tumors and metronidazole. Ann Intern Med. 1981; 94:139-40.
104. Sparrow G, Monton M, Rubens RD et al. Metronidazole in smelly tumours. Lancet. 1980; 1:1185. [IDIS 113870] [PubMed 6103999]
105. Koch RL, Beaulieu BB, Chrystal EJT et al. A metronidazole metabolite in human urine and its risk. Science. 1981; 211:398-9. [IDIS 128360] [PubMed 7221546]
106. Plosker GL. Possible interaction between ethanol and vaginally administered metronidazole. Clin Pharm. 1987; 6:189-93. [IDIS 226467] [PubMed 3665375]
107. Shelly WB, Shelley ED, Burmeister V. Unilateral demodectic rosacea. J Am Acad Dermatol. 1989; 20:915-7. [PubMed 2523912]
109. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(No. RR-11):1-95.
110. Hillier S, Holmes KK. Bacterial vaginosis. In: Holmes KK, Mardh PA, Sparling PF et al, eds. Sexually transmitted diseases. 2nd ed. New York: McGraw-Hill; 1990:547-59.
111. Hillier SL, Lipinski C, Briselden AM et al. Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis. Obstet Gynecol. 1993; 81:963-7. [IDIS 315000] [PubMed 8497364]
112. Livengood CH 3rd, McGregor JA, Soper DE et al. Bacterial vaginosis: efficacy and safety of intravaginal metronidazole treatment. Am J Obstet Gynecol. 1994; 170:759-64. [IDIS 328273] [PubMed 8141197]
113. Colli E, Landoni M, Parazzini F. Treatment of male partners and recurrence of bacterial vaginosis: a randomized trial. Genitourin Med. 1997; 73:267-70. [PubMed 9389947]
114. Anon. Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2004; 2:67-74. [PubMed 15529116]
115. Anon. Topical treatment for bacterial vaginosis. Med Lett Drugs Ther. 1992; 34:109. [PubMed 1435507]
116. Lugo-Miro VI, Green M, Mazur L. Comparison of different metronidazole therapeutic regimens for bacterial vaginosis: a meta-analysis. JAMA. 1992; 268:92-5. [IDIS 298175] [PubMed 1535108]
117. Mardh PA. The vaginal ecosystem. Am J Obstet Gynecol. 1991; 165:1163-8. [PubMed 1951571]
118. Thomason JL, Gelbart SM, Anderson RJ et al. Statistical evaluation of diagnostic criteria for bacterial vaginosis. Am J Obstet Gynecol. 1990; 162:155-60. [PubMed 1689107]
119. Curatek Pharmaceuticals. Clinical monograph on MetroGel-Vaginal (metronidazole vaginal gel). Elk Grove Village, IL; 1992 Dec.
120. Thomason JL, Gelbart SM, Scaglione NJ. Bacterial vaginosis: current review with indications for asymptomatic therapy. Am J Obstet Gynecol. 1991; 165:1210-7. [IDIS 290713] [PubMed 1951577]
121. Larsson PG, Platz-Christensen JJ, Thejls H et al. Incidence of pelvic inflammatory disease after first-trimester legal abortion in women with bacterial vaginosis after treatment with metronidazole: a double-blind, randomized study. Am J Obstet Gynecol. 1992; 166:100-3. [IDIS 290451] [PubMed 1733176]
122. Centers for Disease Control and Prevention, Atlanta, GA: Personal communication.
123. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin: Vaginitis. Number 72. Washington, DC: American College of Obstetricians and Gynecologists; 2006 May.
124. Goldstein EJC, Citron DM, Cherubin CE et al. Comparative susceptibility of the Bacteroides fragilis group species and other anaerobic bacteria to meropenem, imipenem, piperacillin, cefoxitin, ampicillin/sulbactam, clindamycin, and metronidazole. J Antimicrob Chemother. 1993; 31:363-72. [PubMed 8486570]
125. Spiegel CA. Susceptibility of Mobiluncus species to 23 antimicrobial agents and 15 other compounds. Antimicrob Agents Chemother. 1987; 31:249-52. [PubMed 3566250]
126. Jones BM, Geary I, Lee ME et al. Comparison of the in vitro activities of fenticonazole, other imidazoles, metronidazole, and tetracycline against organisms associated with bacterial vaginosis and skin infections. Antimicrob Agents Chemother. 1989; 33:970-2. [IDIS 255730] [PubMed 2764547]
128. Ohm-Smith MJ, Sweet RL, Hadley WK. In vitro activity of cefbuperazone and other antimicrobial agents against isolates from the female genital tract. Antimicrob Agents Chemother. 1985; 27:958-60. [IDIS 201051] [PubMed 4026268]
129. Jones BM, Geary I, Alawattegama AB et al. In-vitro and in-vivo activity of metronidazole against Gardnerella vaginalis, Bacteroides spp. and Mobiluncus spp. in bacterial vaginosis. J Antimicrob Chemother. 1985; 16:189-97. [PubMed 3905748]
130. Ralph ED, Amatnieks YE. Relative susceptibilities of Gardnerella vaginalis (Haemophilus vaginalis), Neisseria gonorrhoeae, and Bacteroides fragilis to metronidazole and its two major metabolites. Sex Transm Dis. 1980; 7:157-60. [PubMed 6779387]
131. Lau AH, Lam NP, Piscitelli SC et al. Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives. Clin Pharmacokinet. 1992; 23:328-64. [PubMed 1478003]
132. Cunningham FE, Kraus DM, Brubaker L et al. Enhanced bioavailability of intravaginally administered metronidazole gel. Pharmacotherapy. 1991; 11:265.
133. Spiegel CA, Eschenbach DA, Amsel R et al. Curved anaerobic bacteria in bacterial (nonspecific) vaginosis and their response to antimicrobial therapy. J Infect Dis. 1983; 148:817-22. [IDIS 179151] [PubMed 6631073]
134. Hill GB. The microbiology of bacterial vaginosis. Am J Obstet Gynecol. 1993; 169:450-4. [PubMed 8357043]
135. Greaves WL, Chungafung J, Morris B et al. Clindamycin versus metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol. 1988; 72:799-802. [IDIS 311380] [PubMed 3050654]
136. Bignardi GE. Clindamycin versus metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol. 1989; 74:281. [IDIS 257823] [PubMed 2748067]
137. Greaves WL. Clindamycin versus metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol. 1989; 74:281-2. [IDIS 257823] [PubMed 2748067]
138. Thomason JL, Gelbart SM, Broekhuizen FF. Advances in the understanding of bacterial vaginosis. J Reprod Med. 1989; 34(Suppl):581-7. [PubMed 2677362]
139. Sweet RL. New approaches for the treatment of bacterial vaginosis. Am J Obstet Gynecol. 1993; 169:479-82. [IDIS 319599] [PubMed 8357050]
140. Ralph ED, Amatnieks YE. Metronidazole in treatment against Haemophilus vaginalis (Corynebacterium vaginale). Antimicrob Agents Chemother. 1980; 18:101-4. [IDIS 122129] [PubMed 6968175]
141. Ralph ED, Austin TW, Pattison FL et al. Inhibition of Haemophilus vaginalis (Corynebacterium vaginale) by metronidazole, tetracycline, and ampicillin. Sex Transm Dis. 1979; 6:199-202. [PubMed 388682]
142. Ralph ED. Comparative antimicrobial activity of metronidazole and the hydroxy metabolite against Gardnerella vaginalis. Scand J Infect Dis. 1983; 40:115-20.
143. Alper MM, Barwin BN, McLean WM et al. Systemic absorption of metronidazole by the vaginal route. Obstet Gynecol. 1985; 65:781-4. [IDIS 199976] [PubMed 4000568]
144. Fredricsson B, Hagström B, Nord CE et al. Systemic concentrations of metronidazole and its main metabolites after intravenous, oral and vaginal administration. Gynecol Obstet Invest. 1987; 24:200-7. [PubMed 3692332]
145. Mattila J, Männisto PT, Mäntylä R et al. Comparative pharmacokinetics of metronidazole and tinidazole as influenced by administration route. Antimicrob Agents Chemother. 1983; 23:721-5. [IDIS 170764] [PubMed 6870221]
146. Palmer RM, Matthews JP, Wilson RF. Adjunctive systemic and locally delivered metronidazole in the treatment of periodontitis: a controlled clinical study. Br Dent J. 1998; 184:548-52. [PubMed 9682550]
147. Lie T, Bruun G, Boe OE. Effects of topical metronidazole and tetracycline in treatment of adult periodontitis. J Periodontol. 1998; 69:819-27. [PubMed 9706861]
148. Anon. Metronidazole. In: Goodman LS, Gilman AG, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 4th ed. New York: The Macmillan Company; 1970:1150-3.
149. Catterall RD. Alternative dosage regimens in trichomoniasis. In: Finegold SY, McFadzean JA, Roe FJC, eds. Metronidazole. Proceedings of the International Metronidazole Conference 1976. Montreal, Canada: Excerpta Medica; 1977:79-82.
150. Gardner HL. Urogenital trichomoniasis. In: Finegold SY, McFadzean JA, Roe FJC, eds. Metronidazole. Proceedings of the International Metronidazole Conference 1976. Montreal, Canada: Excerpta Medica; 1977:72-78.
151. Grossman JH III, Galask RP. Persistent vaginitis caused by metronidazole-resistant trichomonas. Obstet Gynecol. 1990; 76:521-2. [IDIS 270896] [PubMed 2381638]
152. Lossick JG, Kent HL. Trichomoniasis: trends in diagnosis and management. Am J Obstet Gynecol. 1991; 165:1217-22. [IDIS 290714] [PubMed 1951578]
153. Lossick JG. Treatment of sexually transmitted vaginosis/vaginitis. Clin Infect Dis. 1990; 12(Suppl 6):S665-81.
154. Balows A, Hausler WJ, Herrmann KL et al, eds. Manual of clinical microbiology. 5th ed. Washington, DC: American Society for Microbiology; 1991:481,484.
155. Amsel R, Totten PA, Spiegel CA et al. Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983; 74:14-22. [PubMed 6600371]
156. Heine P, McGregor JA. Trichomonas vaginalis: a reemerging pathogen. Clin Obstet Gynecol. 1993; 36:137-44. [PubMed 8435938]
157. Hammill HA. Trichomonas vaginalis. Obstet Gynecol Clin North Am. 1989; 16:531-40. [PubMed 2687745]
158. Seligman SA. Trichomonal vaginitis refractory to conventional treatment. Genitourin Med. 1989; 65:200-1. [PubMed 2759616]
159. Schmitt C, Sobel JD, Meriwether C. Bacterial vaginosis: treatment with clindamycin cream versus oral metronidazole. Obstet Gynecol. 1992; 79:1020-3. [IDIS 296638] [PubMed 1579299]
160. Sobel JD, Schmitt C, Meriwether C. Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J Infect Dis. 1993; 167:783-4. [IDIS 310176] [PubMed 8440952]
161. Andres FJ, Parker R, Hosein I et al. Clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis: a prospective double-blind clinical trial. South Med J. 1992; 85:1077-80. [PubMed 1439943]
162. Depew CC. Manufacturer letter regarding the use of Cleocin vaginal cream for bacterial vaginosis. Kalamazoo, MI: The Upjohn Company; 1992 Nov 25.
163. Higuera F, Hidalgo H, Sanchez CJ et al. Bacterial vaginosis: a comparative, double-blind study of clindamycin vaginal cream versus oral metronidazole. Curr Ther Res. 1993; 54:98-110.
164. Joesoef MR, Hillier SL, Wiknjosastro G et al. Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight. Am J Obstet Gynecol. 1995; 173:1527-31. [IDIS 357323] [PubMed 7503196]
167. Curatek Pharmaceuticals. Common MetroGel Vaginal questions. Elk Grove Village, IL; 1992 Nov.
168. Rothstein E, Clancy DD. Toxicity of disulfiram combined with metronidazole. N Engl J Med. 1969; 280:1006-7. [PubMed 4888076]
169. Goodhue WW Jr. Disulfiram-metronidazole (well-identified) toxicity. N Engl J Med. 1969; 280:1482-3. [PubMed 5786533]
170. Luttor C. Use of a proteolytic ointment (Elase) as adjunctive therapy in the treatment of cervicitis and vaginitis. Curr Ther Res Clin Exp. 1981; 30:621-6.
171. Bro F. Metronidazole pessaries compared with placebo in the treatment of bacterial vaginosis. Scand J Prim Health Care. 1990; 8:219-23. [PubMed 2284521]
172. Edelman DA, North BB. Treatment of bacterial vaginosis with intravaginal sponges containing metronidazole. J Reprod Med. 1989; 34:341-4. [PubMed 2732981]
173. Brenner WE, Dingfelder JR. Metronidazole-containing sponges for the treatment of bacterial vaginosis. Adv Contracept. 1986; 2:363-9. [PubMed 3551523]
174. Schindler EM, Thamm H, Ansmann EB et al. Treatment of bacterial vaginitis: multicenter, randomized, open study with tinidazole in comparison with metronidazole. Fortschr Med. 1991; 109:138-40. [PubMed 2045037]
175. Bistoletti P, Fredricsson B, Hagström B et al. Comparison of oral and vaginal metronidazole therapy for nonspecific bacterial vaginosis. Gynecol Obstet Invest. 1986; 21:144-9. [PubMed 3710287]
176. Reviewers’ comments (personal observations).
177. Curatek Pharmaceuticals, Elk Grove Village, IL: Personal communication.
178. Hillier SL. Diagnostic microbiology of bacterial vaginosis. Am J Obstet Gynecol. 1993; 169:455-9. [PubMed 8357044]
179. Bump RC, Zuspan FP, Buesching WJ III et al. The prevalence, six-month persistence, and predictive values of laboratory indicators of bacterial vaginosis (nonspecific vaginitis) in asymptomatic women. Am J Obstet Gynecol. 1984; 150:917-24. [PubMed 6391177]
180. Galderma. MetroCream (metronidazole) 0.75% topical cream prescribing information. Fort Worth, TX; 2002 Dec.
181. Teicher MH, Altesman RI, Cole JO et al. Possible nephrotoxic interaction of lithium and metronidazole. JAMA. 1987; 257:3365-6. Letter.
182. Gugler R, Jensen JC. Interaction between cimetidine and metronidazole. N Engl J Med. 1983; 309:1518-9. [IDIS 178641] [PubMed 6646177]
183. 3M Pharmaceuticals. Metrogel-Vaginal (metronidazole 0.75% vaginal gel) prescribing information. Northridge, CA; 2003 Jan.
184. Dermik. Noritate (metronidazole 1% topical cream) prescribing information. Berwyn, PA: 2003 Aug.
186. Cunningham FE, Kraus DM, Brubaker L et al. Pharmacokinetics of intravaginal metronidazole gel. J Clin Pharmacol. 1994; 34:1060-5. [IDIS 339092] [PubMed 7876396]
187. G.D. Searle & Co. Flagyl ER (metronidazole extended release tablets) prescribing information. Chicago, IL; 1998 Mar 9.
188. Sobel JD. Vaginitis. N Engl J Med. 1997; 337:1896-903. [IDIS 401347] [PubMed 9407158]
189. Ferris DG, Litaker MS, Woodward L et al. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract. 1995; 41:443-9. [PubMed 7595261]
190. Newton ER, Piper J, Peairs W. Bacterial vaginosis and intraamniotic infection. Am J Obstet Gynecol. 1997; 176:672-7. [PubMed 9077627]
191. McGregor JA, French JI, Seo K. Premature rupture of membranes and bacterial vaginosis. Am J Obstet Gynecol. 1993; 169:463-6. [PubMed 8357046]
192. Hay PE, Lamont RF, Taylor-Robinson D et al. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ. 1994; 308:295-8. [PubMed 8124116]
193. Meis PJ, Goldenberg RL, Mercer B et al. The preterm prediction study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol. 1995; 173:1231-5. [PubMed 7485327]
194. Hillier SL, Nugent RP, Eschenbach DA et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med. 1995; 333:1737-42. [PubMed 7491137]
195. Ferris DG. Management of bacterial vaginosis during pregnancy. Am Fam Physician. 1998; 57:1215-8. [IDIS 403444] [PubMed 9531904]
196. Morales WJ, Schorr S, Albritton J. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol. 1994; 171:345-7. [IDIS 334580] [PubMed 8059811]
197. Hauth JC, Goldenberg RL, Andrews WW et al. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med. 1995; 333:1732-6. [IDIS 357931] [PubMed 7491136]
198. Hack M, Merkatz IR. Preterm delivery and low birth weight—a dire legacy. N Engl J Med. 1995; 333:1772-4. [IDIS 357933] [PubMed 7491144]
199. McGregor JA, French JI, Parker R et al. Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation. Am J Obstet Gynecol. 1995; 173:157-67. [IDIS 350523] [PubMed 7631673]
200. Peipert JF, Montagno AB, Cooper AS et al. Bacterial vaginosis as a risk factor for upper genital tract infection. Am J Obstet Gynecol. 1997; 177:1184-7. [PubMed 9396917]
201. Moi H, Erkkola R, Jerve F et al. Should male consorts of women with bacterial vaginosis be treated? Genitourin Med. 1989; 65:263-8.
202. Vejtorp M, Bollerup AC, Vejtorp L et al. Bacterial vaginosis: a double-blind randomized trial of the effect of treatment of the sexual partner. Br J Obstet Gynaecol. 1988; 95:920-6. [PubMed 3056506]
203. Mengel MB, Berg AO, Weaver CH et al. The effectiveness of single-dose metronidazole therapy for patients and their partners with bacterial vaginosis. J Fam Pract. 1989; 28:163-71. [PubMed 2644391]
204. McGregor JA, French JI, Jones W et al. Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream. Am J Obstet Gynecol. 1994;170:1048-59.
205. duBouchet L, McGregor JA, Ismail M et al. A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis. Sex Transm Dis. 1998; 25:176-9. [PubMed 9524997]
206. Reviewers’ comments (personal observations) on metronidazole 8:40.
207. Galderma. MetroLotion (metronidazole 0.75% topical lotion) prescribing information. Fort Worth, TX; 2003 Aug.
208. Winkel EG, Van Winkelhoff AJ, Timmerman MF et al. Amoxicillin plus metronidazole in the treatment of adult periodontitis patients. A double-blind placebo-controlled study. J Clin Periodontol. 2001 28:296-305.
209. Sigusch B, Beier M, Klinger G et al. A 2-step non-surgical procedure and systemic antibiotics in the treatment of rapidly progressive periodontitis. J Periodontol. 72:275-83.
210. Veien NK, Munkvad JM, Nielsen AO et al. Topical metronidazole in the treatment of perioral dermatitis. J Am Acad Dermatol. 1991; 24:258-60. [PubMed 2007672]
211. Laude TA, Salvemini JN. Perioral dermatitis in children. Semin Cutan Med Surg. 1999; 18:206-9. [PubMed 10468040]
212. Poteete V. case study: eliminating odors from wounds. Decubitus. 1993; 6:43-6. [PubMed 8297491]
213. Witkowski JA, Parish LC. Topical metronidazole gel. The bacteriology of decubitus ulcers. Int J Dermatol. 1991; 30:60-1.
214. Upsher-Smith Laboratories. Vandazole (metronidazole 0.75% vaginal gel) prescribing information. Minneapolis, MN; 2005 May.
215. Anon. Drugs for parasitic infections. Med Lett Drugs Ther. Aug 2004. From the Medical Letter web site ().
216. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2003 report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003.
217. Presutti Laboratories. Tindamax (tinidazole tablets) prescribing information. Arlington Heights, IL; 2004 May 14.
f. AHFS drug information 2006. McEvoy GK, ed. Metronidazole. Bethesda, MD: American Society of Health-System Pharmacists; 2006:3384-9.