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J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Diagnosis And Management Of Infectious

Martin Quan, M.D.

Abstract: Vaginitis is an important gynecologic disorder that accounts for nearly 5 million office visits to physicians each year. Infectious vaginitis is the most common cause for an abnormal ; other possible causes include , , physiologic discharge, physicochemical vaginitis, and psychosomatic vaginitis. Although the history and physical examination may suggest the diagnosis, laboratory confirmation is required. The vaginal pool wet mount remains the cornerstone in the office diagnosis of vaginitis, with the "sniff" test, vaginal pH determination, and the "swab" test all playing important adjunctive roles. is the only effective treatment for in the United States. The vaginal administration of an imidazole agent is the mainstay of treatment of vaginal . Despite a search for alternative drug regimens, a 7-day course of metronidazole therapy remains the treatment of choice for . (J Am Board Fam Pract 1990; 3:195-205.)

Vaginitis is an important and often challeng­ with a vaginal . In a study of more than ing problem in office gynecology. Generally re­ 20,000 women with an "abnormal" discharge, garded as a mundane, benign disorder, vaginitis Fleury found that etiologies other than infectious is nevertheless the source of physical discomfort vaginitis accounted for more than one-third of and psychosocial embarrassment. In an ambula­ cases.4 The of vaginitis is tory setting, nearly 1 percent of are listed in Table 1. prescribed for women with this diagnosis. I Al­ though "shotgun" therapy based on an "eyeball" Physiologic Vaginal DIscharge diagnosis was a common practice in the past, Because 10 percent of patients complaining of modern management of vaginitis demands that a vaginitis may have a physiologic discharge,4 it is specific diagnosis be made. This article reviews important to understand what constitutes a nor­ the clinical aspects of vaginitis and focuses on mal discharge. The normal vaginal discharge the diagnosis and management of infectious consists primarily of exfoliated vaginal squamous vaginitis. and cervical columnar cells suspended in a fluid http://www.jabfm.org/ medium. The vaginal fluid is derived from cervi­ Frequency cal mucus; vulvar secretions from sebaceous, Although exact figures are unavailable, vaginitis sweat, and Bartholin and Skene glands; and is thought to be the most common gynecologic serum transudate from capillaries in the vag­ disorder seen in clinical practice. Gardner esti­ inal wall. 5

mated that vaginal were likely to de­ Clinically, a normal vaginal discharge is a clear on 27 September 2021 by guest. Protected copyright. velop in one-third of all menstruating females. 2 A or opaque white, nonhomogenous, highly viscous national ambulatory medical care survey found suspension that is unassociated with pruritus, that vaginal complaints were responsible for burning, or malodor.6 It is normal for secretions nearly 5 million physician visits per year.'! to increase in volume at the time of ovulation, following , during , and Causes following intercourse.7 In addition, increased vol­ When vaginitis is the suspected diagnosis, it is umes of vaginal secretions may also arise from important to appreciate that the presence of a anxiety, the use of oral contraceptives, cervical vaginal discharge is not necessarily synonymous ectopy, and frequent vaginal douching.8 The indigenous is an ecological system comprising both anaerobic and aerobic From the Division of Family Medicine, School of Medicine, organisms, with the former outnumbering the University of California. Los Angeles. Address reprint requests to Martin Quan, M.D., UCLA Family Health Center, BH-134 latter by a factor of approximately 10. Lactoba­ CHS, \0833 LeConte Avenue, Los Angeles, CA 90024-\683. cilli (or Doderlein bacilli) dominate the facul-

Infectious Vaginitis 195 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Table 1. Differential Diagnosis ofVagiDaI Discharge. percent of cases are caused by , 12 with the remainder caused by other Candida spe­ Physiologic vaginal discharge cies such as Candida glabrata and Candida tropi­ Infectious vaginitis calis. 17 Candida albicans is a dimorphic fungus that Bacterial vaginosis Trichomonas vaginitis is frequently isolated as a commensal on mucocu­ Candida vaginitis taneous surfaces, including the . It is an Atrophic vaginitis opportunistic pathogen that produces vaginitis Cervicitis when it overgrows the bacterial vaginal flora, a Physicochemical vaginitis Allergic-irritant vaginitis development that occasionally can be linked to vaginitis factors altering its environmental milieu, com­ Psychosomatic vaginitis promising local host defenses, or both. Such pre­ Miscellaneous Cervical polyps-neoplasms disposing factors include the reduction of the Condyloma acuminatum normal bacterial population stemming from broad-spectrum use, increased vaginal Vulvar or vaginal neoplasms epithelial glycogen as in pregnancy or uncon­ trolled , as well as excessive perineal heat and moisture associated with the wearing of tative flora, which also includes Staphylococcus tight, insulating clothing.12 epidermidis, diphtheroid bacilli, Group D strepto­ is a unicellular, flagellated cocci, and Escherichia coli. Important anaerobic or­ protozoan that commonly inhabits the lower ganisms include Peptococcus, Peptostreptococcus, an­ genitourinary tract. It is an anaerobic parasite 9 10 aerobic lactobacilli, and Bacteroides species. • that is the third leading cause of infectious vagi­ Despite their pathogenic potential, Gardneretla nitis, accounting for 15 to 30 percent of cases.4.6 vaginalis and Candida albicans are part of the nor­ Although trichomoniasis is sexually transmitted 2 mal flora in up to 50 percent I I and 20 percent I of and acquired in almost all cases, rare nonvenereal women, respectively. transmission is theoretically possible because the organism has been isolated from toilet seats Infectious Vaginitis and can survive in tap water, soap water, bub­ Bacterial vaginosis is the most recent and perhaps ble baths, chlorinated swimming pools, and IR 19 most appropriate term for a clinical entity that hot tubs. • has previously been known by a number of http://www.jabfm.org/ names including nonspecific vaginitis, Hemophilus Atrophic Vaginitis vaginitis, Corynebacterium vaginale vaginitis, non­ Atrophic vaginitis is an inflammatory disorder of specific vaginosis, and Gardneretla vaginitis. It the vagina, a consequence of inadequate has emerged as the number one cause of infec­ production. It is primarily a problem of postmen­ tious vaginitis, accounting for nearly one-half of opausal women but may be seen in lactating and IJ

cases. Bacterial vaginosis is a synergistic, poly­ prepubertal patients as well. The hypoestrogenic on 27 September 2021 by guest. Protected copyright. microbial, superficial vaginal infection character­ state causes "thinning" of the vaginal , ized by a reduction in the concentration of lacto­ making it more susceptible to trauma and second­ bacilli and concomitant overgrowth of both ary bacterial invasion. anaerobic bacteria (particularly Peptococcus, Bac­ teroides, and Mobiluncus species) and Gardneretla Cervicitis vaginalis to a concentration 100 to 1000 times Cervicitis is a common though oftentimes over­ higher than normal. I 1.14 Trimethylamine, putres­ looked cause of an abnormal discharge. Fleurl cine, and cadaverine are among the amines elabo­ reported that nearly one-fourth of women com­ rated in excess by the anaerobic overgrowth and plaining of vaginal discharge had cervicitis in­ probably are responsible for the fishy malodor, stead. virus, trachoma­ which is the hallmark of this infection. I 5 tis, and are the major Vaginal candidiasis is a common problem that infectious causes of cervicitis, with the latter two affects up to 75 percent of women at least once responsible for nearly one-half of cases of muco­ ltI 20 during their reproductive years. Eighty to 90 purulent cervicitis.

196 JABFP July-September 1990 Vol. 3 No.3 Physicochemical Vaginitis ish, occasionally bloody discharge in a postmeno­ J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Allergic-irritant vaginitis can arise from almost pausal woman should immediately arouse suspi­ any agent that comes in contact with the vagina. cion of atrophic vaginitis. Likewise, a pruritic, Agents capable of eliciting vaginal white, curdlike discharge in a woman with his­ include genital soaps, preparations, bub­ tory of recent antibiotic or steroid use, preg­ ble baths, genital deodorants, spermicidal agents, nancy, or diabetes suggests vaginal candidiasis. and intravaginal medications. 21 Sexual transmis­ Following the history, a thorough gyneco­ sion of IgE antibodies in semen has recently been logic examination should be performed. This implicated by Wit ken and coworkers as a possible should include not only careful inspection of cause of allergic vaginitis. 22 the discharge but the vulvovaginal and cervical Although more commonly seen in the pre­ areas. Vaginal erythema and edema are indica­ adolescent girl, foreign body vaginitis can occur tive of an inflammatory vaginal process, while a in adult women as well. Wads of toilet tissue and mucopurulent cervical discharge coupled with cotton are commonly responsible in children, a friable, inflamed is pathognomonic for whereas forgotten , contraceptive de­ cervicitis. vices, pessaries, and sexual implements are com­ Although clinical findings may suggest a diag­ monly implicated in adults. nosis, they generally lack the sensitivity and specificity to be used as the sole basis for diagno­ Psychosomatic Vaginitis sis. For example, pruritus, usually a symptom of Psychosomatic vaginitis is an elusive diagnosis candidiasis, can be absent in 25 percent24 and that accounts for up to 2 percent of patients with present in 48 percent of those with Trichomonas vaginitis. h is primarily a diagnosis of exclusion vaginitis and 13 percent of those with bacterial 25 that should be considered in patients who have vaginosis. ,26 Similarly, vaginal malodor, the completely normal examinations and laboratory hallmark of bacterial vaginosis, can be absent in 27 evaluations. Hallmarks of this disorder, first de­ one-third ,28 and present in 50 percent of those scribed by Dodson and Friedrich,23 are: (1) per­ with vaginal trichomoniasis. 29 Finally, the pres­ sistent symptoms of longstanding duration, ence of a "" (punctate sub­ (2) lack of demonstrable pathology, (3) sexual in­ epithelial hemorrhages) is pathognomonic for activity as a direct result of symptoms, (4) unsuc­ trichomoniasis but seen in only 2 to 3 percent of cessful consultations with multiple physicians, cases. JO his evident that the laboratory must play

(5) "" to many common vaginal prepara­ a pivotal role in the diagnosis of suspected http://www.jabfm.org/ tions, (6) reluctance to accept the suggestion of a vaginitis. psychophysiologic cause, and (7) emotionallabil­ Table 2. Information Useful in the Evaluation of Vaginitis. ity and dependency.

Age Miscellaneous Menstrual status Characteristics of discharge

Less common causes of an abnormal vaginal dis­ on 27 September 2021 by guest. Protected copyright. charge include cervical polyps or neoplasms, Onset macerated condyloma acuminatum, rectovaginal Color Texture fistulas, and vulvar and vaginal neoplasms. Viscosity Odor Clinical Evaluation Associated symptoms Vaginal Patients with vaginitis generally have complaints Pruritis of vaginal irritation, vaginal discharge, or both. Important historical information to elicit from History of diabetes mellitus, genitourinary infections such patients is presented in Table 2. Bacterial Medication use vaginosis typically produces a grayish, malodor­ Method of contraception ous discharge, whereas a copious, frothy, yellow­ Sexual history green discharge is characteristically associated Marital status Number of partners with vaginal trichomoniasis. Vaginal soreness Feminine hygienic practices and dyspareunia in association with a thin, gray-

Infectious Vaginitis 197 Laboratory Evaluation J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Vaginal Pool Wet Mount The vaginal pool wet mount is the most impor­ tant tool in the office diagnosis of vaginitis. The optimal time for performing this examination is while the patient is experiencing symptoms. It is important that the patient abstain from douching for at least 2 days before the examination and not to insert an intravaginal medication or contraceptive for at least 5 days.·1 I The test entails the micro­ scopic examination of the vaginal discharge, first with the low-power (x (00) objective and then with the high-power (x 4(0) objective. Two vagi­ Figure 2. Photomicrograph of a saline wet mount showing an nal slides are generally examined, one with saline excessive number of white cells. and the other with potassium hydroxide (KOH). The saline slide is prepared by mixing a small sample of the discharge with a few drops of fresh, physiologic saline and then covering the suspen­ identification of this extracellular parasite on sa­ sion with a coverslip. The microscopic examina­ line wet mount (Figure 3).33 Trichomonas vaginalis tion of a normal vaginal discharge shows many is a pear-shaped organism slightly larger than a vaginal epithelial cells with sharply defined cellu­ white cell that is readily identified by its jerky, lar and nuclear borders (Figure I), an abundance flagellate motility and undulating membrane. Be­ of large gram-positive rods (lactobacilli), and a cause trichomonads become round when they die few white cells (WCs). An excessive number of and are indistinguishable from white cells, it is white cells (generally defined as either more than important that the saline is fresh and that the one per epithelial cell or more than ten per high­ slide is examined as soon after preparation as power field) is indicative of an inflammatory possible . .14 process (Figure 2) and suggestive of cervicitis or A "clue cell" is an exfoliated vaginal epithelial trichomoniasis. 12 A variable number of white cell that appears under light to be cells are seen in patients with candidiasis, and a heavily stippled or granular in appearance be­

reduced number are generally seen in patients cause of the adherence of gram-negative coccoba­ http://www.jabfm.org/ with bacterial vaginosis. cilli to its surface. An obscure cellular outline is The diagnosis of vaginal trichomoniasis is an important diagnostic feature of a clue cell, dis­ made in 50 to 90 percent of affected women by tinguishing it from a normal vaginal epithelial cell (Figure 4). The presence of "clue cells" sub­ stantiates the diagnosis of bacterial vaginosis and is found in 90 percent of cases. 27 on 27 September 2021 by guest. Protected copyright. The KOH slide is prepared by mixing a sam­ ple of the discharge with a few drops of 10 per­ cent KOH. The KOH dissolves the epithelial elements on the slide (a process accelerated by gently heating the slide), facilitating the iden­ tification of fungal elements. The identifica­ tion of pseudohyphae and budding forms (spores) confirms the presence of Candida albicans (Figure 5), whereas the finding of only spores with the absence of pseudohyphae (mycelia) sug­ gests the presence of Candida glabrata. The re­ Figure 1. Photomicrograph of a saline wet mount preparation ported sensitivities of the KOH slide for detect­ demonstrating a normal vaginal epithelial cell. Note the dis­ ing vaginal candidiasis range from 21 to 94 tinct cell border and the discernable nuclear outline. percent. 35-.17

198 JABFP July-September 1990 Vol. 3 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Eschenbach and colleagues l9 reported a vaginal pH greater than 4.7 in nearly 50 percent of pa­ tients attending a sexually transmitted diseases clinic, excluding those with bacterial vaginosis and trichomoniasis. The diagnostic value of this test is invalidated if the sample is contaminated with blood, cervical mucus, semen, amniotic fluid, or a douche preparation.

"Swab" Test The "swab" test was first proposed in 1984 by Brunham and coworkers41l as a means of confirm­ Figure 3. Photomicrograph of a saline wet mount showing ing the diagnosis of mucopurulent cervicitis. It is Trichomonas vaginalis. a simple test that is performed by collecting en­ docervical mucus on a white-tipped swab (taking care to avoid contamination by vaginal secre­ "SnUT" Test tions) after wiping the ectocervix clean with a The "sniff" test (or "whiff" test) is a simple test large cotton swab. A positive result is indicated that detects the presence of certain amines arising by either a "yellow" appearance of the cervical from abnormal vaginal anaerobic metabolism. A mucus on the swab or the presence of 10 or more positive test, defined as the production of a polymorphonuclear leukocytes in five nonadja­ "fishy," aminelike odor when to percent KOH is cent fields on Gram stain of the endocervical added to the vaginal discharge sample, occurs as mucus. the result of increased volatility of the odorifer­ ous amines with elevation of the pH. A positive Vaginal Stained Smears result substantiates the diagnosis of bacterial va­ Stained smears of vaginal secretions are not rou­ ginosis and is found in 67 to 76 percent of tinely performed in the evaluation of vaginitis 27 cases. ,2X However, this test is not specific for but can be of value in certain patients. For exam­ this infection and can be positive in other anaero­ ple, a Hansel stain can detect and quantitate the bic states, such as vaginal trichomoniasis. 3H presence .of eosinophils in the vaginal secre­ tions. 21 Eosinophilia in the vaginal discharge, http://www.jabfm.org/ VaginalpH greater than 25 percent, has been found by Ricer 41 Determination of the vaginal pH is a simple to indicate allergic vaginitis. though often overlooked diagnostic aid that is a valuable adjunct to the wet mount preparation. It is performed by placing a drop of the discharge onto commercial pH paper and interpreting the on 27 September 2021 by guest. Protected copyright. resultant color. The vaginal sample should be ob­ tained from the lateral or posterior fornix of the vagina, taking special care to avoid sampling the cervical mucus. I I In the menstrual woman, the normal vaginal pH is slightly acidic (pH 3.5 to 4.5) as a result of lactic acid production by lactobacilli. Ninety-two percent of normal women have been found to have a vaginal pH of less than 4.7. 1.1 A pH greater than 4.5 is considered abnormal and is present in 81 to 97 percent of patients with bacterial vagi no­ 27 39 sis • and more than 60 percent of patients with Figure 4. Photomicrograph of a saline wet mount showing a Trichomonas vaginitis. lO An abnormally alkaline clue ceD (arrow). Note how the ceD border and nuclear out· pH, however, is a relatively nonspecific finding; line are obscured by the adherent coccobacilli.

Infectious Vaginitis 199 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Genital Cultures Vaginal cultures have a limited role in the diag­ nosis of vaginitis and are best used on a selective basis. Vaginal cultures should be strongly consid­ ered in patients with persistent or recurrent vaginitis, particularly when a definitive diag­ nosis could not be made on the basis of the pre­ viously described tests. When trichomoniasis is suspected clinically, but the wet mounts are re­ peatedly negative, confirmation of this diagnosis can be made by culturing the discharge on either Kupferberg medium or Diamond Medium Modi­ Figure 5. Photomicrograph of a potassium hydroxide wet fied™.n Similarly, the Sabouraud or Nickerson mount showing pseudohyphae characteristic of Candida medium can be used to identify Candida infec­ albicans. tion. Because can be recov­ ered from normal women and is but one compo­ nent of a polymicrobial infection, isolation of this Several investigators have found the vaginal organism adds little to the clinical picture and is Gram stain smear to be an accurate means of rarely, if ever, helpful for making a diagnosis. diagnosing bacterial vaginosis.II,3<),42 Gram stain Patients with suspected cervicitis, a purulent criteria for bacterial vaginosis are Gardnerella vaginal discharge, or both, warrant evaluation for morphotypes (small, gram-variable bacilli) and at the presence of Neisseria gonorrhoeae and Chlamydia least one other morphotype (gram-positive cocci, trachomatis. The diagnosis of is best curved rods, gram-negative rods, or fusiforms) in made on culture, using a modified Thayer-Mar­ amounts of five or more per oil immersion field tin medium. Although cultures remain the most with fewer than five morphotypes sensitive and accurate method for detecting Chla­ (large gram-positive bacilli) per oil immersion mydia, antigen detection systems (e.g., direct field. A vaginal Gram stain is classified as normal immunofluorescent test, enzyme immunoassay if lactobacillus morphotypes are present in test) have been developed that are not only more amounts greater than five or more per oil immer­ convenient but have a reported sensitivity rang­ sion field, alone or in combination only with ing from 70 to 98 percent and specificity exceed­ http://www.jabfm.org/ Gardnerella morphotypes. Although found by ing 90 percent.44 Spiegel, et al. 42 to possess excellent sensitivity and specificity for bacterial vaginosis, the diag­ Management of Infections Vaginitis nostic accuracy of the vaginal Gram stain is likely Trichomonas Vaginalis to vary with the skill and experience of the A definitive diagnosis of Trichomonas vaginitis can microscopist. be made by either identifying motile trichomon­ on 27 September 2021 by guest. Protected copyright. ads on the wet mount preparation or by a positive Vaginal Hormone Cytology culture. If trichomonads are absent on the wet Vaginal hormone cytology has been used for mount and cultures are unavailable, a presump­ many years to evaluate the estrogen status of tive diagnosis can be made in patients with a postmenopausal women. It is a cytological tech­ compatible clinical picture (abnormal vaginal dis­ nique that samples a minimum of 200 vaginal charge, elevated pH, and excessive number of epithelial cells obtained from the lateral wall of white cells) provided the possibility of cervicitis the midportion of the vagina, classifying them is adequately excluded.45 into one of three cell types: parabasal, intermedi­ Metronidazole, a 5-nitroimidazole derivative ate, and superficial. An increased proportion of first introduced in 1960, remains the only effec­ parabasal cells (i.e., maturation value of less than tive treatment for trichomoniasis in the United 40 percent or parabasal cells exceeding 20 per­ States. The single 2-gram dose is effective in 86 cent) characterizes a hypoestrogenic state and to 97 percent of cases25 .4(;,47 and is favored by substantiates the presence of atrophic vaginitis.43 most clinicians because of easy administration,

200 JABFP July-September 1990 Vol. 3 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from better compliance, and lower cost. However, sexual contacts. Although empiric treatment of nausea and vomiting can be a problem with this the man partner is generally favored,2,lo,12,H the regimen, affecting 4 to 16 percent of treated pa­ diagnosis of trichomoniasis in the man can be tients. 25 ,47 Alternatively, the traditional 7-day confirmed on microscopic examination of the regimen of 250 mg three times daily can be con­ sediment of a first-void morning urine specimen sidered, particularly in those intolerant of or who or of a urethral discharge obtained spontaneously fail the single 2-gram treatment. Cure rates re­ or following prostatic massage. Because studies ported for the 7-day treatment range from 81 to have shown concomitant infection with gonor­ 98 percent.25 rhea in 20 to 50 percent of women with trichomo­ Metronidazole-resistant strains of Trichomonas niasis,45 both the patient and her sexual con­ vagina/is are rare but must be considered in pa­ sort(s) warrant examination for gonorrhea and tients refractory to standard treatment. After ex­ other STDs. cluding noncompliance and reinfection from an untreated partner, Trichomonas cultures and Vaghud Candidiasis susceptibility testing to metronidazole can be Management of symptomatic vaginal candidiasis done. The treatment options in patients with re­ in the United States has generally relied on topi­ sistant trichomoniasis include prescribing a higher cal polyene and imidazole antifungal agents. In dose of metronidazole (i.e., 500 mg three times the past, candidiasis called for nystatin, a polyene daily for 10 to 14 days), combined oral and intra­ antibiotic, at a dose of 100,000 units intravagi­ vaginal metronidazole therapy, and intravenous nally twice daily for 14 days. During the past metronidazole.4H,49 decade, the imidazoles replaced nystatin as the Adverse reactions to metronidazole include mainstay of treatment, producing cure rates of 85 nausea, dysgeusia, headache, dizziness, periph­ to 95 percent. IO,32 Effective vaginal regimens em­ eral neuropathy, and reversible neutropenia. Met­ ploying imidazoles include: (1) butoconazole ni­ ronidazole can produce a disulfiramlike reaction trate - 100 mg daily for 3 days; (2) miconazole when alcohol is consumed during therapy; thus, nitrate - 100 mg daily for 7 days or 200 mg daily patients need to abstain from alcoholic beverages for 3 days; (3) clotrimazole-l00 mg daily for for at least 24 hours following the last dose. 7 days, 200 mg daily for 3 days, or 500 mg imme­ Metronidazole has been shown to be muta­ diately; and (4) terconazole - 20 mg daily for genic in bacteria and carcinogenic and tumori­ 7 days or 80 mg daily for 3 days.24,52-54 In addi­ genic in mice and rats receiving long-term, high tion to the local adverse effects (e.g., vaginal ­ http://www.jabfm.org/ doses of the drug.4H Studies in humans have not ing, burning) occurring infrequently with all shown metronidazole to be a significant car­ these agents, tlulike symptoms (e.g., transient cinogen but have been deemed inadequate to ex­ headache, chills, , and hypotension) have clude the possibility of delayed oncogenic poten­ been reported in some patients treated with tial.4H.5o Because human teratogenicity remains terconazole. 5 5

uncertain, metronidazole should be avoided dilf­ Less commonly used agents for the treatment on 27 September 2021 by guest. Protected copyright. ing pregnancy and is absolutely contraindicated of vaginal candidiasis include boric acid powder in the first trimester. In pregnant patients, intra­ and gentian violet. In a study by Van Slyke, vaginal clotrimazole (100 mg daily for 7 days) can et al.,37 the daily intravaginal administration of provide symptomatic relief and may effect a cure 600 mg boric acid powder in a gelatin capsule for in 48 to 66 percent of patients . .13 When metroni­ 14 days yielded a cure rate of 92 percent 7 to 10 dazole is required in a lactating woman, it should days after treatment and 72 percent 30 days after be administered as a single 2-gram oral dose, and treatment. Although messy and occasionally irri­ breast-feeding should be withheld for 24 hours tating, the topical application of 1 percent aque­ after the dose to permit adequate maternal excre­ ous solution of gentian violet to the vulvovaginal tion of the drug. 51 area is also considered an effective form of Because trichomoniasis is a sexually transmit­ treatment. 19 ted disease (STD), examination and simulta­ For patients with persistent or recurrent Can­ neous treatment with either the single dose or dida vaginitis, predisposing factors should be 7-day regimen is recommended for the patient's identified and, if possible, eliminated. Such pre-

Infectious Vaginitis 201 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from disposing factors include unrecognized or poorly can produce but also its implication as a risk fac­ controlled diabetes mellitus, antibiotic or cortico­ tor for pelvic inflammatory disease and certain steroid use, a Candida genital infection in the pa­ obstetric complications (e,g., preterm labor, post­ tient's sex partner, and the wearing of tight, re­ partum , and post-Cesarean endo­ strictive, synthetic underclothing. When these metritis).39,6o,61 A 7-day course of metronidazole, factors have been adequately excluded, fungal 500 mg orally twice daily, remains the treatment cultures may be of value by detection of a Candida of choice for bacterial vaginosis, with a cure rate species likely to be resistant to the usual antifun­ exceeding 97 percent immediately after therapy gal agents. 17 For example, effective management and 86 to 94 percent 4 weeks after therapy.2H,62,63 of Candidaglabrata may require the use of gentian Cost, compliance, and drug safety have violet/,19 and may require topi­ spurred a search for shorter though equally effec­ cal treatment with 5-flucytosine.56 tive courses of metronidazole treatment. The Repeated courses of topical anticandidal agents most effective of these is the two-dose regimen are commonly employed for patients with recur­ reported by Jerve and associates.63 In their multi­ rent candidiasis. These agents can be adminis­ center Norwegian study, metronidazole given tered either at the first sign of infection or on an orally as a single 2-gram dose on days 1 and intermittent, prophylactic basis. Davidson and 3 produced a 94 percent cure rate determined 5 Mould ? concluded that a once-a-month, 7-day 4 weeks from the start of therapy. Three- and course of intravaginal clotrimazole was effective 5-day regimens have also been studied and judged in alleviating symptoms associated with recur­ inferior to the standard 7-day regimen on the rent candidiasis. In a recent study, Sobel, et al. 5H basis of clinical recurrence rates 29 days post­ reported a one-third reduction in recurrence therapy.64 Studies investigating the efficacy of a rates in patients treated with an intravaginal single 2-gram dose have yielded mixed results,65 500-mg clotrimazole tablet administered once a with most investigators reporting a higher failure month. rate for the single dose 3 to 4 weeks after treat­ In patients who fail to respond to topical ther­ ment.62 ,64,66 The use of vaginal metronidazole apy, prophylactic therapy with oral ketoconazole sponges in the treatment of bacterial vaginosis is is the final therapeutic option. In a prospective currently under investigation, with a recent clini­ study of 74 women with recurrent vulvovaginal cal trial reporting an 88 percent rate of cure candidiasis, Sobel 16 found that cyclic ketocona­ 4 weeks after therapy.67 zole (400 mg daily for 5 days beginning with the A number of alternative drugs have been stud­ http://www.jabfm.org/ onset of menses for six menstrual cycles) pre­ ied in the treatment of bacterial vaginosis, but vented recurrences in more than 70 percent none has matched the efficacy of metronidazole. of patients and that continuous low-dose ther­ Intravaginal sulfonamide creams were commonly apy (100 mg daily for 6 months) was successful prescribed in the past but have since been shown in 95 percent of patients. Although clearly to be effective in only 14 to 56 percent of patients.

the most effective treatment available, enthu­ , 100 mg twice daily for 7 days, has on 27 September 2021 by guest. Protected copyright. siasm for ketoconazole is tempered by the cost, produced equally mixed results, with rates of as well as hepatotoxicity (seen primarily in pa­ cure ranging from 14 to 64 percent.2H ,6H Ampicil­ tients more than 50 years) associated with its lin, 500 mg four times daily for 7 days, effectively prolonged use. 16,59 treats 34 to 46 percent of patients and is con­ sidered the drug of choice in pregnant patients. Bacterial Vaginosis In a recent double-blind study by Greaves, The diagnosis of bacterial vaginosis can be made et al.,69 7 days of , 300 mg twice reliably if at least three of the following four cri­ daily, yielded a cure rate (94 percent) 7 to 10 teria are met: (1) the presence of a thin and days after treatment that was comparable with homogenous-appearing vaginal discharge, (2) a the standard 7-day metronidazole regimen; how­ vaginal pH exceeding 4.5, (3) a positive "sniff" ever, whether clindamycin is as effective in re­ test, and (4) clue cells on saline wet mount exam i­ ducing recurrence (or relapse) rates during the H nation. ,27 The importance of effective treatment month following completion of therapy still re­ for this condition lies not only in the symptoms it mains to be determined.

202 JABFP July-September 1990 Vol. 3 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from Controversy continues to exist whether the 3. Cypress BK. Patient's reasons for visiting physi­ man consort(s) of the patient with bacterial cians: National Ambulatory Medical Care Survey: vaginosis requires simultaneous treatment. De­ United States, 1977-78. Vital and Health Statistics. spite a study by Mengel, et al.,65 which concluded Series 13, No. 56. Hyattsville, Maryland: National that treatment of the man partner produced a Center for Health Statistics, U.S. Depanment of Health and Human Services; DHHS Pub. No. short-term reduction in recurrence rate, other (PHS) 82-1717. 1981:1-128. studies have failed to report a benefit from simul­ 4. Fleury FJ. Adult vaginitis. Clin Obstet Gynecol taneous treatment. H,62,64 At the present time, it 1981; 24:407-38. appears reasonable to reserve treatment of the 5. Huggins GR, Preti G. Vaginal odors and secretions. man partner to instances of recurrent infections Clin Obstet Gynecol 1981; 24:355-77. in the woman. 6. Eschenbach DA. Vaginal infection. Clin Obstet Gynecol 1983; 26: 186-202. Summary 7. Hurd JK Jr. Vaginitis. Med Clin North Am 1979; Vaginitis is a common outpatient problem that 63:423-32. represents a diagnostic challenge. It is a disorder 8. Paavonen J, Stamm WE. Sexually transmitted dis­ that is responsible for an estimated 5 million phy­ eases. Lower genital tract infections in women. In­ sician visits per year, accounting for nearly 1 per­ fect Dis Clin Nonh Am 1987; 1:179-98. cent of antibiotics prescribed in the ambulatory 9. Larsen B, Galask RP. Vaginal microbial flora: com­ setting. Infectious vaginitis is the most common position and influences of host physiology. Ann In­ diagnosis made in patients seeking care for an tern Med 1982; 96(pt 2):926-30. 10. Hammill HA. Normal vaginal flora in relation to "abnormal" discharge, with most of the remain­ vaginitis. Obstet Gynecol Clin North Am 1989; ing cases caused by cervicitis, physiologic dis­ 16:329-36. charge, atrophic vaginitis, and physicochemical 11. Weaver CH, Mengel MB. Bacterial vaginosis. J Fam vaginitis. Although the history and physical ex­ Pract 1988; 27:207-15. amination may suggest a diagnosis, confirmation 12. Sobel JD. Epidemiology and pathogenesis of recur­ by simple office tests should be performed rou­ rent vulvovaginal candidiasis. Am J Obstet Gynecol tinely. The vaginal pool wet mount is the most 1985; 152:924-35. important diagnostic test, with adjunctive roles 13. Vontver LA, Eschenbach DA. The role of Gardner­ played by measurement of the vaginal pH, the ella vaginalis in nonspecific vaginitis. Clin Obstet "sniff' test, and the "swab" test. For patients with Gynecol 1981; 24:439-60. persistent or recurrent vaginitis in whom a de­ 14. Spiegel CA, Amsel R, Eschenbach D, Schoenknect http://www.jabfm.org/ finitive diagnosis cannot be made on the basis of F, Holmes KK. Anaerobic bacteria in nonspecific vaginitis. N Engl J Med 1980; 303:601-7. these tests, vaginal stained smears and genital 15. Brand JM, Galask RP. Trimethylamine: the sub­ cultures should be performed. Effective manage­ stance mainly responsible for the fishy odor often ment for vaginal trichomoniasis continues to be associated with nonspecific vaginitis. Obstet Gyne­ metronidazole, prescribed either in a single-dose col 1986; 68:682-5. regimen or an extended 7-day course. The imida­ 16. Sobel JD. Recurrent vulvovaginal candidiasis. on 27 September 2021 by guest. Protected copyright. zole antifungal agents have emerged as the treat­ N EnglJ Med 1986; 315:1455-8. ment of choice for vaginal candidiasis. A 7-day 17. Horowitz BJ, Edelstein SW, Lippman L. Candida tropi­ course of metronidazole is the gold standard of calis vulvovaginitis. Obstet Gynecol 1985; 66:229-32. treatment for vaginosis. 18. Whittington MJ. Epidemiology of infections with Trichomonas vaginalis in the light of improved diag­ References nostic methods. Br J Vener Dis 1957; 33:80-91. I. Gardocki GJ. Use of antimicrobial drugs in office­ 19. Friedrich EG Jr. Vaginitis. Am J Obstet Gynecol based practice, United States, 1980-1981. Vital and 1985; 152:247-51. Healtb Statistics. Series 13, No. 85. Hyattsville, 20. PaavonenJ, Robens PL, Stevens CE, et al. Random­ Maryland: National Center for Health Statistics, ized treatment of mucopurulent cervicitis with doxy­ U.S. Department of Health and Human Services; cycline or . Am J Obstet Gynecol 1989; DHHS Pub. No. (PHS) 86-1746.1986:1-53. 161:128-35. 2. Gardner HL. Infectious vulvovaginitis. In: Monif 21. Ricer RE, Guthrie RM. Allergic vaginitis, a possibly GR, ed. Infectious diseases in and gynecol­ new syndrome. A case report. J Reprod Med 1988; ogy. Philadelphia: Harper & Row, 1982:515-41. 33:781-3.

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the cause of genitourinary symptoms in women in a 50. Beard CM, Noller KL, O'Fallon WM, Kurland LT, on 27 September 2021 by guest. Protected copyright. family practice. Comparison of clinical examination Dokerty MB. Lack of evidence for due to use and comprehensive microbiology. JAMA 1984; of metronidazole. N Engl J Med 1979; 301 :519-22. 251 :620-5. 51. Erickson SH, Oppenheim GL, Smith GH. Metro­ 36. McLennan MT, Smith JM, McLennan CEo Diagno­ nidazole in breast milk. Obstet Cynecol 198 I; sis of vaginal and trichomoniasis. Reliability 57:48-50. of cytologic smear, wet smear and culture. Obstet 52. Droegemueller W, Adamson DG, Brown D, et al. Gynecol 1972; 40:231-4. Three-day treatment with butoconazole nitrate for 37. Van Slyke KK, Michel VP, Rein MF. Treatment of vulvovaginal candidiasis. Obstet Gynecol 1984; vulvovaginal candidiasis with boric acid powder. Am 64:530-4. J Obstet Cynecol 1981; 141:145-8. 53. Fleury F, Hughes D, Floyd R. Therapeutic results 38. Chen KC, Amsel R, Eschenbach DA, Holmes KK. obtained in vaginal mycoses after single-dose treat­ Biochemical diagnosis of vaginitis: determination of ment with 500 mg c1otrimazole vaginal tablets. Am J diamines in vaginal fluid. J Infect Dis 1982; 145: Obstet Gynecol 1985; 152:968-70. 337-45. 54. Kjaeldgaard A, Larsson B. Single-blind comparative 39. Eschenbach DA, Hillier S, Critchlow C, Stevens C, clinical trial of short-term therapy with terconazole

204 JABFP July-September 1990 Vol. 3 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.3.3.195 on 1 July 1990. Downloaded from versus cIotrimazole vaginal tablets in vulvovaginal of metronidazole for symptomatic bacterial vagina­ candidiasis. Curr Ther Res 1985; 38:939-44. sis. JAMA 1985; 254: 1046-9. 55. Moebius UM. Influenza-like syndrome after tercon­ 63. jerve F, Berdal TB, Bohman P, et al. Metronidazole azole [letter]. Lancet 1988; 2:966-7. in the treatment of non-specific vaginitis (NSV). Br j 56. Horowitz BJ. Topical flucytosine therapy for Vener Dis 1984; 60:171-4. chronic recurrent Candida tropicalis infections. j Re­ 64. Eschenbach DA, Critchlow CW, Watkins H, et al. A prod Med 1986; 31:821-4. dose-duration study of metronidazole for the treat­ 57. Davidson F, Mould RF. Recurrent genital candidosis ment of nonspecific vaginosis. Scand j Infect Dis in women and the effect of intermittent prophylactic 1983; 40(SuppI):73-80. treatment. Br j Vener Dis 1978; 54:176-83. 65. Mengel MB, Berg AO, Weaver CH, et al. The effec­ 58. Sobel jD, Schmitt C, Meriwether C. Clotrimazole tiveness of single-dose metronidazole therapy for pa­ treatment of recurrent and chronic candida vulvo­ tients and their partners with bacterial vaginosis. vaginitis. Obstet Gynecol 1989; 73: 330-4. j Fam Pract 1989; 28:163-71. 59. Lake-Bakaar G, Scheuer Pj, Sherlock S. Hepatic 66. Purdon A jr, Hanna jH, Morse PL, Paine DD, En­ reactions associated with ketoconazole in the gel kirk PG. An evaluation of single-dose metronida­ United Kingdom. Br Med j [Clin Res] 1987; 294: zole treatment for Gardnerella vaginalis vaginitis. Ob­ 419-22. stet Gynecol 1984; 64:271-4. 60. Watts DH, Krohn MA, Hillier SL, Eschenbach DA. 67. Edelman DA, North BB. Treatment of bacterial Bacterial vaginosis as a risk factor for post-cesarean vaginosis with intravaginal sponges containing endometritis. Obstet Gynecol 1990; 75:52-8. metronidazole. j Reprod Med 1989; 34: 341-4. 61. Gravett MG, Nelson HP, De Rouen 1', Critchlow C, 68. Malouf M, Fortier M, Morin G, DubejL. Treatment Eschenbach DA, Holmes KK. Independent associ­ of Hemophilus vaginalis vaginitis. Obstet Gynecol ations of bacterial vaginosis and Chlamydia trachoma­ 1981; 57:711-4. tis infection with adverse pregnancy outcome. JAMA 69. Greaves WL, Chungafung j, Morris B, Haile A, 1986; 256:1899-903. Townsend jL. Clindamycin versus metronidazole in 62. Swedberg j, Steiner jF, Deiss F, Steiner S, Driggers the treatment of bacterial vaginosis. Obstet Gynecol DA. Comparison of single-dose vs. one-week course 1988; 72: 799-802. http://www.jabfm.org/ on 27 September 2021 by guest. Protected copyright.

Infectious Vaginitis 205