Vaginitis and cervicitis

Lactobacillus crispatus Escherichia coli Atopobium vaginae
L. jensenii Enterobacter aerogenes Bacteroides fragilis
L. gasseri E. agglomerans Bifidobacterium
L. vaginalis E. cloacae Prevotella bivia
L. iners Klebsiella oxytoca Fusobacterium
Staphylococcus aureus K. pneumoniae Mobiluncus
S. epidermidis Morganella morganii Megasphaera
Streptococcus agalactiae Gardnerella vaginalis Sneathia
S. pyogenes Peptococcus Peptostreptococcus

Note: E. agglomerans is now known as Pantoea agglomerans.

Table 60.2 Categories of the indigenous vaginal microflora

1. Healthy vaginal microflora – Lactobacillus dominant

2. Aerobic vaginal microflora – dominated by facultative anaerobes

3. Bacterial vaginosis – dominated by obligate anaerobes

4. Lactobacillosis – overgrowth of Lactobacillus

Lactobacillus crispatus, L. jensenii, and L. gasseri are the three most common species found in the vagina of women with a “healthy vaginal microflora.” Patients with L. iners, even in the presence of L. jensenii and/or L. gasseri appear to have an unstable microflora and are likely to develop “aerobic vaginitis (AVF)” or BV. The direction in which the vaginal microflora will drift and eventually become established appears to be dependent upon whether or not Gardnerella vaginalis is present as a member of the indigenous vaginal microbiota.

One mechanism provided by Lactobacillus crispatus, L. jensenii, and L. gasseri is the production of lactic acid. Lactic acid results in maintaining the vaginal pH < 4.5. This acidic pH favors the growth of Lactobacillus and inhibits the growth of facultative and obligate anaerobic bacteria. When lactobacilli are dominant this results in a ratio of lactobacilli to pathogenic bacteria of 1000:1. The concentration of lactobacilli is 106 bacteria/mL of vaginal fluid. This ratio of lactobacilli to pathogenic bacteria is important when considering a surgical procedure on a patient whose vaginal microflora is dominated either by a gram-positive or gram-negative facultative anaerobe or by obligate anaerobes, i.e. when pathogenic bacteria predominate. When the vaginal microflora is disrupted in such a way, especially in the patient undergoing pelvic surgery, transvaginal ovum retrieval, cesarean section, or who has preterm premature rupture of amniotic membranes leading to delivery of a premature fetus, all such patients are at significant risk for the development of a postoperative infection. Therefore, patients undergoing pelvic surgery who have a Lactobacillus-dominant indigenous vaginal microflora are likely to derive benefit from surgical antibiotic prophylaxis because of their risk of infection.

A second mechanism is the production of H2O2 by many species of Lactobacillus, especially L. crispatus, L. jensenii, and L. gasseri; most strains of L. iners do not produce H2O2. Hydrogen peroxide is toxic to obligate anaerobes because they do not produce catalase. Hydrogen peroxide can be converted to super oxide, which can disrupt DNA. Thus, the production of lactic acid and H2O2 appears to work in concert with a third factor, bacteriocin, which is a low-molecular-weight protein that has antibacterial properties. The bacteriocin produced by Lactobacillus, known as Lactocin, has been demonstrated to inhibit the growth of Gardnerella and Prevotella as well as other bacteria.

The cause of an alteration in the indigenous vaginal microflora is unknown. However, one change in the vaginal environment that appears to be instrumental in the disruption of a Lactobacillus-dominant indigenous vaginal microflora is a change in the vaginal pH. When the pH rises, growth of Lactobacillus slows and when pH is between 4.5 and 5, this appears to be a transitional zone. If G. vaginalis is present the microflora is destined to develop into BV. If Gardnerella is not present then it may well develop into “aerobic vaginitis.” This is an important concept to understand because when the gram-negative bacteria are dominant there is an increase in TNF-α in the vagina. Thus, an inflammatory state is created and conditions such as BV are associated with increased risk of an infection in the upper genitalia tract as well as an increased risk of contracting sexually transmitted diseases, e.g., HIV. This inflammatory response involves the endocervical epithelium, making this tissue more receptive to contracting sexually transmitted organisms. In addition, patients with an altered vaginal microflora, e.g., BV, are at increased risk of developing a postoperative pelvic infection when undergoing pelvic surgery.

Bacterial vaginosis

BV can be defined as a vaginal microflora that is dominated by obligate anaerobic bacteria. The diagnosis can be established easily with very little cost to the patient and consuming no more than 5 minutes of the physician’s time. The clinical criteria are rather easy to determine (Table 60.3) and differentiate the most common types of vaginitis or vaginosis, and can assist in determining proper management. The patient should be reevaluated 1 to 2 weeks after completing treatment to determine if the pH has returned to the acidic range (pH > 3.8 to 4.5) and if large bacilli are present. If the pH 5 and microscopic examination of the vaginal discharge does not reveal the presence of large bacilli, the patient’s initial vaginitis or vaginosis can reoccur or a different type of vaginitis can evolve. This can occur if the patient is diagnosed with BV and treated with metronidazole or clindamycin. The antibiotic will suppress the anaerobic bacteria and may suppress lactobacilli, allowing the facultative anaerobes to flourish if the pH is not decreased to < 5.

Table 60.3 Diagnosis of an altered vaginal microflora

Healthy Aerobic vaginitis Bacterial vaginosis
Bacteria Lactobacillus Facultative anaerobes Obligate anaerobes
Discharge color White to slate-gray Dirty-gray to purulent Dirty-gray
Odor None None Fish-like (Foul)
Microscopic analysis
Squamous cells Cytoplasmic membrane easily identified Clue cells present
Nucleus easily identified Nucleus obscured
WBC <5/hpf <5/hpf <5/hpf
Bacteria Large bacilli May be one morphotype or multiple morphotypes Multiple morphotypes

Abbreviations: hpf = high-power field.

Mycoplasma and Ureaplasma are commonly found to be part of the indigenous vaginal microbiota in patients with a Lactobacillus-dominant vaginal microflora, aerobic vaginitis, or BV. Mycoplasma and Ureaplasma are found in approximately 60% of sexually active individuals. It is not understood how or if these bacteria have a role either in maintaining a healthy vaginal microflora or acting in concert with one or more of the pathogenic bacteria to create an environment that favors the growth of the pathogenic bacteria. Thus, there is much speculation regarding the potential role of Mycoplasma and Ureaplasma; however, other than nongonococcal and non-chlamydial urethritis, and perhaps cervicitis, treatment should not be initiated for these bacteria.

An organism that has gained significant attention is L. iners, which seems to be common in patients with an altered vaginal microflora. In addition, L. iners appears to rarely be present when L. crispatus is dominant. L. iners has been reported to be present when L. jensenii and L. gasseri are dominant. In this latter situation the vaginal microflora appears to be unstable and more easily undergoes shifts in the vaginal microbiota.

BV is made up of a variety of obligate anaerobes which can reach concentrations of >108 bacteria/mL of vaginal fluid, mainly pathogenic bacteria. Undoubtedly there are facultative anaerobes present but probably fewer than 105 bacteria/mL of vaginal fluid. This concentration of bacteria is important because this is an enormous inoculum and can initiate or contribute to significant infection.

Treatments of BV are not very adequate because of the high recurrence rates (Table 60.4). The typical treatments are all designed to suppress the growth of obligate anaerobic bacteria. Treatments may have a suppressive effect on lactobacilli and not suppress the facultative anaerobic bacteria. However, if the pH does not decrease (<4.5) lactobacilli will not grow and either the obligate anaerobic bacteria or facultative anaerobic bacteria will gain dominance. This is the reason that the patient should be re-evaluated within one to two weeks following treatment. The two key observations that are indicative of whether there was resolution or not are: (1) has the vaginal pH returned <4.5, and (2) are large bacilli present. If the pH 5 and no large bacilli are present then patient has not responded in a positive manner. Patients who fail to respond should be referred to a gynecologist who has an interest in vulvovaginal disease.

Table 60.4 Treatments for bacterial vaginosis

Metronidazole 500 mg orally twice a day for 7 days, or

Metronidazole gel 0.75%, one full applicator (5 g) intravaginally hs × 7 days, or

Clindamycin cream 2%, one full applicator (5 g) intravaginally hs × 3 days, or

Tinidazole 2 g orally once daily for 2 days, or

Tinidazole 1 g orally once daily for 5 days, or

Clindamycin 300 mg orally twice a day for 7 days, or

Clindamycin ovules 100 mg intravaginally once at hs × 3 days

CDC MMWR, Sexually Transmitted Diseases Treatment Guidelines, December 17, 2010; 59: 1–110.

Patients with BV who have greater than 5 WBCs/40× magnifications (wet prep) should be considered to have an infection and should be evaluated for Trichomonas vaginalis, Chlamydia trachomatis, and Neisseria gonorrhoeae. BV is dominated by gram-negative obligate anaerobes and probably gram-negative facultative anaerobes. The cell wall of gram-negative bacteria contains LPS, the substance that initiates a proinflammatory response. It has been shown that patients with BV have an increased concentration of TNF-α in the vaginal milieu. The increase in TNF-α indicates that BV may not be a condition that initiates a classic inflammatory response, namely a significant increase in WBCs, but is associated with a possible upregulation of the cytokine cascade. This may be significant in patients who develop an infection, e.g., pelvic inflammatory disease, or who are having significant pelvic surgery, placing the patient at significant risk for developing a postoperative pelvic infection.

Aerobic vaginitis

This condition may have a variety of presentations, bacteriologically; that is, dominance can be unimicrobial, e.g., Streptococcus agalactiae (group B streptococcus, GBS) or Escherichia coli or other unimicrobial vaginitis, or polymicrobial vaginitis. This condition does not resemble BV in that there are no clue cells, often noted as a purulent discharge indicating an inflammatory reaction, and either one bacterial morphotype, e.g., cocci in chains indicating dominance by streptococci or morphologically similar small rods, e.g. E. coli, or a variety of morphotypes indicating a polymicrobial condition. Typically the discharge is odorless. Many gynecologists do not advise obtaining a specimen for culture because whatever bacterium or bacteria is recovered is part of the normal vaginal microflora. However, obtaining a culture does assist: (1) in differentiating BV from aerobic vaginitis, (2) in determining which bacterium or bacteria is dominant, and (3) in determining if it is a mixed gram-positive and gram-negative vaginal microbiota. Without determining the microbiology, it would be difficult to administer appropriate treatment. The treatment most frequently administered, without bacteriologic data, is either metronidazole or

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Jun 18, 2016 | Posted by in INFECTIOUS DISEASE | Comments Off on Vaginitis and cervicitis

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