Chlamydia trachomatis
Authors: Julius Schachter, Ph.D.
Microbiology
Chlamydia trachomatis is one of several species within the genus Chlamydia that cause human disease, but it is the only one that only infects humans. The others are discussed elsewhere in this volume. C. pneumoniae is an important human pathogen, while C. psittaci, the cause of psittacosis is common in avian species, but infects humans only as a zoonosis. Person to person transmission is rare.
Chlamydiae are obligate intracellular bacteria that cannot be cultured on artificial media. Susceptible cell culture systems are needed to grow them in the laboratory. Chlamydiae are distinguishable from all other organisms by a unique developmental cycle which involves transition between 2 major morphologic forms (19). The infectious particle, called the elementary body (EB), attaches to susceptible host cells and is ingested by a process akin to receptor mediated endocytosis. It enters the cell within an endosome and remains there throughout the cycle. Chlamydiae inhibit phagolysosomal fusion. Approximately 6 -8 hours after entering the cell the elementary body changes to the reticulate body (RB, sometimes called an initial body). This represents the metabolically active and reproductive form of the organism. Reticulate bodies are not infectious. They divide by binary fission up to approximately 48 hours into the cycle. At some time between 24-48 hours, some of the reticular bodies reorganize again into elementary bodies and thus become infectious. Ultimately, the cell will burst and the elementary bodies exit the host cell to infect new cells. The full cycle will take approximately 48 hours for the more virulent lymphogranuloma venereum biovar; and 72-96 hours for the trachoma biovar.
C. trachomatis strains can be divided into two biovars. The trachoma biovar is a pathogen of columnar and squamocolumnar cells and thus causes disease at mucous membranes, where such cells are found. These sites include conjunctivae, urethra, the endocervical canal, fallopian tubes, gastrointestinal and respiratory tracts. The less common lymphogranuloma venereum (LGV) biovar is more virulent. It is more invasive and can cause disease in many tissues. Lymphogranuloma venereum strains will infect epithelial cells, as the primary lesion for this infection is often in the skin, and it will grow within macrophages. The organism will subsequently invade draining lymph nodes and cause the formation of bubos. The 2 biovars are readily differentiated in the laboratory as lymphogranuloma venereum strains are capable of cell to cell transmission in cell culture and are capable of lethal infection following intracranial inoculation in mice while the trachoma biovar is not lethal for mice by this route and does not grow well in cell culture systems. It requires mechanical assistance (centrifugation) for efficient infection. There are laboratory developed nucleic acid amplification tests (NAATs) that can identify the specific biovars. The commercially available nucleic acid amplification tests used for diagnosing C. trachomatis infection will not differentiate the biovars. There are 15 serovars/genovars (with many subtypes) but only the biovar differentiation is clinically relevant. The A, B, Ba and C serovars are associated with trachoma, D-K serovars with genital infection, and L1, L2 and L3 are the major lymphogranuloma venereum serovars.
There are several aspects of C. trachomatis microbiology that are relevant to treatment. The organism is an obligate intracellular parasite and is metabolically active only after it enters the host cell. The infectious elementary body is metabolically inert, and thus not affected by antibiotics. Therefore, only antibiotics that penetrate cells will be effective against C. trachomatis. Because the developmental cycle is so long (typically 2 -4 days), long courses of therapy are required. In addition, although C. trachomatis is a bacterium, it does not contain a peptidoglycan layer (structural rigidity appears to depend on disulfide binding among at least three outer membrane proteins). A lack of peptidoglycan predicts that ß-lactam antibiotics will not be effective in treating chlamydial infections. Experience has shown that most of these drugs are not efficient in treating C. trachomatis infections, although high doses and long courses of therapy may be active (amoxicillin is the exception, and has been used for treating chlamydial infections during pregnancy) (1, 7). C. trachomatis does contain penicillin binding sites and in vitro the action of penicillin is to induce large irregularly shaped reticulate particles, as the antibiotics appear to interfere with the division process (3, 40).
Epidemiology
There appear to be two major modes of transmission of C. trachomatis. In industrialized Western society, virtually all C. trachomatis infections are sexually transmitted. C. trachomatis is now considered to be the most common sexually transmitted bacterial pathogen, and it is the most common infection reported to the CDC (5). In the United States, it is estimated that more than 3 million new infections occur each year. If untreated, the infections can persist for years, but will ultimately clear. The highest prevalence of chlamydial infections is usually found in sexually active teenagers. Young age is usually the strongest risk factor for these infections. At least 60% to 70% infants exposed to C. trachomatis by passage through the infected birth canal will acquire the infection.
It has become obvious that the prevalence of C. trachomatis among men who have sex with men (MSM) has been underestimated. The reason is that standard procedures in STD clinics have been based on testing males for urethral infections. Expanding screening to include routine rectal and oropharyngeal testing will more than double the number of men who have sex with men found to have chlamydial infection (16, 27). A paradigm shift is called for, and CDC has recommended such screening (38). A proviso is that nucleic acid amplification tests (NAATs) must be used due to the insensitivity of culture and other diagnostic methods (21).
Lymphogranuloma venereum has been considered as a disease of tropical climes, typified by genital ulcers and inguinal buboes in men. That lymphogranuloma venereum proctitis occurs in men who have sex with men has been known for many decades. In the early 2000s what seemed to be an epidemic of lymphogranuloma venereum proctitis was identified in the Netherlands. Classical bubonic disease was rarely seen. The disease was identified because molecular methods to identify the lymphogranuloma venereum biovar were used, as these men were being seen in the context of STD clinic studies where C. trachomatis was common. The disease was soon identified throughout Western Europe, and genotyping methods identified what seemed to be a new variant, called L2b (32). The large outbreak among men who have sex with men appears to be clonal. But L2b was only new in the context of when it was identified. Testing of a library of C. trachomatis isolates obtained in the early 1980s from men who have sex with men in San Francisco found that L2b was common in men who have sex with men then (33). It seems that L2b has been in circulation within the gay community for at least several decades.
In trachoma endemic areas, C. trachomatis is usually spread from child to child. In many developing countries, trachoma is endemic and in some areas it is hyper- or holoendemic. In the past there were hundreds of millions at risk for trachoma and millions have been blinded. The disease has disappeared from many countries as a function of improved sanitation and the environmental changes associated with industrialization. It is still a problem in some developing countries, with an estimated 60 million at risk, and remains the world's leading infectious cause of blindness. In holoendemic areas, children acquire the infection early. In some communities, all are infected by 2 years of age. Blindness occurs much later in adulthood.
Clinical Manifestations
Asymptomatic infections are common in both men and women. This is one of the reasons that control efforts have stressed screening of high risk individuals. In men, C. trachomatis causes 35% to 50% of nongonococcal urethritis (38). There is usually a mucopurulent discharge and dysuria. Ascending infections occur and C. trachomatis is the leading cause of epididymitis in sexually active young men. In women, the most commonly affected site is the cervix, where the organism can cause a mucopurulent endocervicitis. Ascending genital infection is even more common in women. C. trachomatis is found in the endometrium or fallopian tubes of approximately 25% of cases of acute salpingitis, or pelvic inflammatory disease (PID) in the United States. Asymptomatic endometritis/salpingitis is common and is important from a public health viewpoint as many of the women with long term complications of pelvic inflammatory disease, such as ectopic pregnancy, have no history of pelvic inflammatory disease (4, 37).
Rectal and oropharyngeal infections occur in both men and women. They are a particular problem in men who have sex with men. Testing for them has not been routine, but the infections are common. Chlamydial rectal infections in men who have sex with men occur with a frequency similar to gonococcal infections, often being found in 8%-12% of high risk men being seen in clinics (27). These infections are usually asymptomatic, but proctitis is seen in some men who have sex with men. Oropharyngeal chlamydial infection is less common than gonococcal infection in high risk men who have sex with men, typically being found in 1%-2% of these men as compared to 8%-12% for the gonococcus. These extragenital infections in women have been less well studied, and the clinical manifestations are not well defined. But even when the prevalence of infections is high, most have been described as asymptomatic.
Lymphogranuloma venereum proctitis has a broader clinical spectrum. Here too, asymptomatic infection is common. But severe proctocolitis can occur, as the biovar is more invasive. Some of these infections may be seen in medical clinics rather than STD clinics because some men may have constipation, fevers, chills and weight loss.
About one in three infants born through a Chlamydia -infected birth canal develops inclusion conjunctivitis of the newborn. It is a mucopurulent conjunctivitis with an incubation period of 5 to 21 days. Approximately one in six exposed infants develops a characteristic pneumonia syndrome when between 2 and 12 weeks old. The infants often have a prodrome of rhinitis and many have conjunctivitis. Affected infants are usually afebrile, are markedly tachypenic and occasionally apneic, and have a staccato cough.
Trachoma is a chronic follicular keratoconjunctivitis. Repeated, or persistent infections can cause conjunctival scarring. Over time, these scars can contract, resulting in lid distortion which in turn results in eyelashes abrading the cornea (entropion and trichiasis). This mechanical damage, often complicated by corneal bacterial infection, is what causes blindness.
Laboratory Diagnosis
Many chlamydial infections are managed on a syndromic basis. For example, urethritis in men is often managed by ruling out gonorrhea (by Gram stain of urethral discharge or swab) and then treating for chlamydia if the smear is negative. Where specific diagnosis is required (it is always advisable) the tests of choice are the commercially available nucleic acid amplification tests. These tests are far more sensitive than earlier diagnostic methods and are highly specific for C. trachomatis. Because they can be used with noninvasively collected specimens (such as first catch urines or vaginal swabs) they are particularly well suited for screening of asymptomatic individuals.
Culture (which is not widely available, and is relatively insensitive) is only recommended when detecting the infection will have legal ramifications, such as in child abuse. Serology is not useful for routine diagnosis of chlamydial infection. Detection of IgM antibodies to the organism is useful in diagnosing chlamydia pneumonia in infants.
Experience in Sweden with the use of nucleic acid amplification tests to diagnose C. trachomatis infection has led to changes in the way nucleic acid amplification tests are designed. Many manufacturers used DNA sequences within the C. trachomatis cryptic plasmid as targets for their nucleic acid amplification tests. This was popular because the plasmid is virtually ubiquitous among wild strains, and is present at 4-8 copies per elementary body thus providing a sensitivity advantage. What happened in Sweden is that a mutant with a 377bp deletion in the plasmid appeared (23). The deleted region included the target sequence used in some nucleic acid amplification tests. Thus this Swedish variant (Sv) escaped detection by some of the nucleic acid amplification tests used for diagnosis and screening. It was discovered when some parallel testing was done with nucleic acid amplification tests that had different targets. Fortunately the Swedish variant that escaped detection due to failure of the diagnostic tests did not appear to have any biological advantage (22). It became quite common in Sweden, and was seen in other Scandinavian countries, but did not get established elsewhere. Needless to say, manufacturers quickly redesigned their assays to detect Swedish variant , and the current generation of nucleic acid amplification tests for chlamydial DNA is including two targets to protect against possible future target changes. A fringe benefit, not currently being exploited, is that when nucleic acid amplification tests have two targets a positive result could (software allowing) have internal confirmation of that positive result.
Pathogenesis
There is evidence that chlamydial diseases result in part from hypersensitivity or are diseases of immunopathology. A common pathologic end point of chlamydial infection is scarring of mucous membranes. This is what ultimately leads to the blindness in trachoma and to infertility and ectopic pregnancy after acute salpingitis. Current theory suggests that it is hypersensitivity to their heat shock protein (HSP60) that is responsible for much of chlamydial pathology. Repeat, and long lasting infections are likely to lead to worse outcomes.
SUSCEPTIBILITY IN VITRO AND IN VIVO
Single Drug
There is no generally accepted way of determining antimicrobial susceptibility patterns for C. trachomatis. The general approach is to use relatively low infectious inoculum in susceptible cells and to titrate the quantity of antibiotic that will reduce inclusion counts by 50, 90, or 100% in that initial growth cycle. This is the method used to determine inhibitory levels. Cidal levels are determined by doing a subculture from the antibiotic treated cells into antibiotic-free cells to determine the lowest concentration of antibiotic that prevents subsequent recovery of the organism.
The most active antibiotics against C. trachomatis are in the rifampin group. However, these drugs are not used clinically, because resistance develops rapidly in vitro (24).
In general, the MIC of antibiotics in cell culture systems predicts the clinical responses seen in humans. Thus tetracyclines are highly active in vitro and are highly useful clinically. Macrolides show lesser activity in vitro, yet are considered clinically active. Quinolones have borderline levels of activity and some are considered to be clinically active while others are not useful in treating human infections. Table 1 lists typical antimicrobial susceptibility levels for a variety of common antibiotics for C. trachomatis.
Combination Drugs
In general, combinations of drugs are not used for C. trachomatis infection. Where commonly used drugs often show synergy with other infections, the activity with C. trachomatis appears to be additive rather than synergistic.
Antimicrobial Resistance
Some laboratory workers have generated some evidence of antibiotic resistance in clinic settings (14, 31). This "heterotypic resistance" was identified using high titer inoculum in vitro tests for susceptibility and is likely to be more a function of the assay than a reflection of relevant resistance. It is identified by the finding of chlamydial inclusions in the presence of the antibiotic. Further passage of these does not result in establishing resistant strains, but rather sees a loss of infectivity. Most, if not all, chlamydial isolates will show heterotypic resistance if a high enough inoculum is used in the assays.
Quinolone resistance may be developed in the laboratory and is due to specific mutations in genes encoding for the DNA gyrase A enzyme (8). The importance of this observation is mitigated by the fact that these drugs are not drugs of choice
Treatment failures do occur, but even where there are treatment failures the isolated strains tend to be susceptible and infections tend to respond to second courses of therapy. Thus, at the moment, antimicrobial resistance obviously remains a possibility but is not of major concern. For example, earlier reports of relative resistance to erythromycin in vitro have not been clinically relevant (20). Efforts to eliminate blinding trachoma as a public health problem include community wide treatment with azithromycin. C. trachomatis isolates obtained after communities were subjected to multiple rounds of oral azithromicin remained fully susceptible to azithromycin (35).
Thus the big question is why do treatment failures occur? It is reasonable to speculate that the answer comes from the organism's developmental cycle. It is known that antibiotics can induce aberrant reticular bodies. These are giant forms that are stopped from completing the transition to elementary bodies. Removal of the antibiotic allows completion. The host response to infection can do the same thing because the effects of gamma interferon are similar. Thus it is likely that during an infection there may be some infected cells where the infection is not actively in the developmental sequence, and thus not susceptible to the actions of antibiotics. This will be temporary, hence the success of retreatment.
ANTIMICROBIAL THERAPY
Drug of Choice
For many years, tetracyclines have been considered the drugs of choice for treating C. trachomatis infections. Doxycycline has been preferred because of the presumption of improved compliance. Courses of therapy have ranged from 7-21 days, depending on the disease being treated. This changed when a single 1 gm dose of oral azithromycin was shown to be as effective as week-long courses of doxycycline, in treatment of uncomplicated chlamydial genital tract infection (18). Recommended protocols are listed in Table 2. This drug has also been used in treating chlamydial infections in pregnant women (13, 15). In addition a single 1 gm dose of oral azithromycin has also been shown to be as effective as long (30 days - 6 week) courses of topical tetracycline ointment in the treatment of hyperendemic trachoma (2). It is possible that ultimately azithromycin will be considered the drug of choice in treating all chlamydial infections. Currently where this is not the case it is because of absence of relevant treatment trials. Week-long courses of doxycycline and a single 1 gm dose of azithromycin have been found to be 96-98% effective in curing chlamydial infection as determined by isolation in cell culture.
Ofloxacin (but not all other quinolones) is effective in treating chlamydial infections. In general, erythromycin is considered the back-up drug for those who cannot take tetracycline. This of course applies to settings where azithromycin may not be used because of cost concerns. For example, in treating chlamydial infections in infected infants (dosages are shown in Table 2) it is considered the first line treatment.
Azithromycin has now been shown to be highly effective in treating chlamydial infection in pregnancy (13, 15). It is not a drug which will likely be explicitly approved for use in pregnancy, but with lack of reported complications it has become accepted as the drug of choice in this setting, replacing erythromycin. Amoxicillin is considered the alternative drug for pregnant women who are erythromycin intolerant. A substantial proportion of pregnant women will suffer GI upset to the extent that it will cause them to cease their courses of erythromycin. In this setting, amoxicillin is the appropriate alternative regimen and has been shown to be highly effective.
The regimens listed below, and in Table 2, are modified from the CDC STD treatment guidelines (38).
Special Situations
Lymphogranuloma Venereum
The lymphogranuloma venereum biovar of C. trachomatis is highly invasive and can cause many different clinical manifestations although the classical presentation in males is of inguinal bubos with or without systemic manifestations of infection (26). More typical today is rectal infection in men, and this is often asymptomatic. There is a paucity of controlled treatment trials for this disease. In general, long courses of therapy (at least 21 days) are called for. Treatment failures are not uncommon and the usual approach is to retreat using an alternate regimen. The recommended regimen is doxycycline at 100 mg b.i.d. for 21 days. The alternate regimen is erythromycin, 500 mg b.i.d. for 21 days.
Genital Tract Infection
The trachoma biovar has a more limited spectrum of susceptible cells; causes diseases at mucous membranes; and is an important cause of urethritis and epididymitis in men. In women, it causes lower genital tract infection and more importantly it will infect fallopian tubes, where the resultant damage may cause such sequelae as tubal factor infertility and ectopic pregnancy (36). C. trachomatis is considered the most common sexually transmitted bacterial infection. It is estimated that in the United States, more than 3 million infections occur each year (5).
The recommended regimens are azithromycin, a single 1 gm oral dose: or doxycycline 100 mg b.i.d. for 7 days. Alternate regimens include erythromycin, 500 mg, q.i.d. for 7 days; or erythromycin ethylsuccinate, 800 mg, q.i.d. for 7 days; ofloxacin 300 mg, b.i.d. for 7 days; or levofloxacin 500 mg for 7 days.
It should be emphasized that all cases of pelvic inflammatory disease should be treated with a regimen of multiple antibiotics that includes a drug active against C. trachomatis.
Pregnant Women
Treatment of chlamydial infection in pregnancy is recommended to prevent post-partum complications and perinatal infections (28). The treatment of choice is a single 1 gm oral dose of azithromycin (13, 15). An alternate is erythromycin, 500 mg, q.i.d. for 7 days. Because a 2 gm per day dose of erythromycin may not be well tolerated by pregnant women, an alternate regimen involves a smaller daily dose of 250 mg q.i.d. with extension of treatment to 14 days. Similarly, erythromycin and ethylsuccinate can be used at 800 mg, orally, q.i.d. for 7 days; or 400 mg, orally, q.i.d. for 14 days.
Where relatively large numbers of patients have been tested following amoxicillin regimens, tests of cure have shown that failure rates are equivalent to, or less than, those seen with erythromycin (1, 7). This drug is not considered a drug of choice for treatment of chlamydial infection in pregnancy only because of the theoretical concerns that most researchers have that ß-lactam drugs can often suppress, but not eradicate, chlamydial infection. That caveat has not translated into actual demonstration of persistent or inapparent infections, even though many of the tests of cure were performed late enough that such infections should have been detected.
Chlamydial Infections in Infants
Infants exposed during the birth process by passing through the infected birth canal may develop conjunctivitis and/or pneumonia (25). Conjunctivitis is typically seen in the first 3 weeks of life, while pneumonia generally occurs in the first 3-4 months after birth. The drug of choice for the treatment of these infections is azithromycin, 20 mg/kg/day orally, 1 dose daily for 3 days. The alternate is erythromycin, 12.5 mg/kg, 4 times daily, for 10 -14 days.
ENDPOINTS FOR MONITORING THERAPY
It is generally considered that tests of cure are not required for evaluating treatments for chlamydial infection. With adequate compliance, cure rates in the upper 90 percentile range are expected. Using single doses of oral azithromycin may remove the compliance concern. Where there may be an indication that tests of cure are important, there are certain caveats that must be considered. With some antibiotic regimens it is possible to suppress chlamydiae and render early tests of cure inaccurate. Thus, it is inappropriate to perform a test of cure one week after treatment has been completed. It is more prudent to wait at least three weeks after treatment to assess potential failures. This, of course, introduces a problem of potential re-infection. That potential is most marked in sexually transmitted infections where re-exposure to untreated partners or infected others within the same group may result in a positive test as a result of reinfection rather than treatment failure.
The appropriate microbiologic test for use to assess treatment efficacy may also present a problem. However, the exquisite sensitivity of nucleic acid amplification tests, particularly given the revelation that urine can be an appropriate specimen for diagnosing chlamydial infection in both men and women, suggests that urine specimens tested by nucleic acid amplification tests may be an appropriate way to perform tests of cure. The caveat here is that chlamydia DNA has been detected for at least 3 weeks after treatment has begun (in the absence of recoverable viable organism by culture), thus it is necessary to wait at least that long before performing tests of cure (39). A well designed follow-up study to assess test of cure by using two different nucleic acid amplification tests (one detecting chlamydial DNA, the other, RNA) demonstrated how difficult it is to establish appropriate endpoints. They collected 18 specimens over 8 weeks post treatment, and found differing results by the nucleic acid amplification tests and so much variation and intermittent positivity as to put doubt on any routine post 3 week test of cure (9). This is not surprising given the options possible during an 8 week post treatment period: eradication of infection; slow shedding of infected cells; straightforward treatment failure; suppression followed by exacerbation; introduction of chlamydial nucleic acid in ejaculate; and reinfection.
Clinical response may be a useful endpoint, but may also be misleading. For example, it is well known that somewhere between 10 -15% of men with nongonococcal urethritis will not respond to tetracycline, erythromycin or azithromycin therapy. These men do not have persistent chlamydial infection, or recurrent chlamydial infection. Typically, if they had chlamydial infection at the beginning of therapy, that infection is cured but they have other causes (i. e., non nongonococcal-non-chlamydial urethritis) of inflammation. Mycoplasma genitalium has emerged as a leading cause of nongonococcal, non-chlamydial urethritis.
VACCINES
While much progress has been made in developing experimental vaccines, there are no vaccines commercially available, and the experimental vaccines have not been successful enough to move into human trials.
PREVENTION OR INFECTION CONTROL MEASURES
A prevention program for reduction of genital chlamydial infection and its complications has been presented by CDC. It is largely based on screening of sexually active asymptomatic populations that represent the reservoir of infection. Routine screening in family planning clinics has been shown to reduce prevalence of infection and incidence of subsequent acute salpingitis. Annual screening of sexually active women < 25 years of age is the centerpiece of the program. Women above that age, with risk factors (such as new, or multiple partners) should also be screened. Annual screening is also recommended for MSM who engage in risky behaviors. Individuals who have been diagnosed with C. trachomatis infection are at high risk of reinfection, and screening at 3 month intervals is recommended. Efforts to reduce risky behaviors and promotion of condom use may also prevent infection. Routine screening of pregnant women, and treatment of those who are infected will prevent perinatal infection (28). In trachoma endemic areas community wide treatment with azithromycin has been shown to dramatically reduce chlamydial infection rates (29).
Success of the chlamydia control programs has been mixed. Coverage has been varied, with routine screening of young women reaching about 50%-60% of eligible women. Assessment of programs has been challenging. Acute salpingitis, ectopic pregnancy and perinatal infections seem to have been reduced. But in many populations chlamydial prevalence has been increasing slightly. A hypothesis has been presented that the increase is due to "arrested immunity" where treatment shortens the duration of an infection that would otherwise naturally result in a relative immunity to infection (4). Thus more of the at risk population is susceptible. It is difficult to measure this. Part of the increased prevalence is certainly due to use of more sensitive nucleic acid amplification tests, and part is likely due to reaching more high risk populations. It has been suggested that screening of males should be introduced.
There is a major effort to eliminate blinding trachoma as a public health problem. This is based on application of a multipronged approach, the SAFE strategy (Surgery, Antibiotics, Facial cleanliness, Environmental improvement). Surgery is performed to correct lid deformities that might otherwise cause blindness in the near future. The antibiotic component is community wide treatment with azithromycin to reduce chlamydial infection in the community. Pfizer has been donating the antibiotic for the program, and more than 444 million doses have been distributed. The facial cleanliness and environmental improvement focus on improving personal hygiene and providing latrines to limit transmission of infection spread from residual or newly introduced infection. Some countries have declared success, but there are large challenges remaining (12).
CONTROVERSIES
One controversy relates to the belief by some that chlamydia persists in non-replicating forms in infected patients and that these forms are not affected by antibiotics. Thus, persistent chlamydial infections exists as a state and total cure is not possible. Suffice it to say that the author does not subscribe to these beliefs. Non-replicating forms do exist, but are more likely to cause a temporary treatment failure than to cause a lifelong infection.
Another controversy revolves around questions of reduced treatment efficacy (17). Particular concern has been placed on the success, or lack of success, of azithromycin in treating C. trachomatis urethritis or perhaps of greater concern, rectal infection (10, 11, 30, 34). We urgently need appropriately designed randomized clinical trials to provide the answers.
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Tables
Table 1. Minimum Inhibitory Concentration (MIC) of Antimicrobial Agents for C. trachomatis
| Drug | MIC (mg or U/ml) |
|---|---|
| Rifampin | 0.005-0.25 |
| Tetracyclines | 0.03-1 |
| Azithromycin | 0.03-1 |
| Erythromycin | 0.1-1 |
| Ofloxacin | 0.5-1 |
| Ampicillin | 0.5-10 |
| Penicillin | 1-10 |
| Sulfamethoxazole | 0.5-4 |
| Clindamycin | 2-16 |
| Spectinomycin | 32-100 |
| Gentamicin | 500 |
| Vancomycin | 1,000 |
Table 2. Treatment of Chlamydial trachomatis Infections.
Condition |
First Choice |
Second Choice |
||
|---|---|---|---|---|
| Drug |
Dose |
Drug |
Dose |
|
| Genital tract infections (e.g., urethritis, cervicitis) | Azithromycin | 1 g. orally, single dose | Doxycycline | 100 mg, b.i.d. x 1 wk |
| LGV | Doxycycline | 100 mg, b.i.d. x 21 days | Erythromycin | 500 mg, q.i.d. x 21 days |
| Pregnant women | Erythromycin | 250 mg, q.i.d. x 2 wk | Amoxicillin | 500 mg, t.i.d. x 1 wk |
| Infant pneumonia | Erythromycin | 12.5 mg/kg, q.i.d. x 2 wk | Sulfisoxazole | 37.5 mg/kg, q.i.d. x 2 wk |
| Inclusion conjunctivitis (Infants) | Erythromycin | 12.5 mg/kg, q.i.d. x 2 wk | Sulfisoxazole | 37.5 mg/kg, q.i.d. x 2 wk |
| Inclusion conjunctivitis (Adults) | Tetracycline | 250 mg, q.i.d. x 3 wk | Erythromycin | 250 mg, q.i.d. x 3 wk |
Note: The above guideline reflects the CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2002 as well as other sources.
What's New
Seña AC, et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis Infections in Men With Nongonococcal Urethritis: Predictors and Persistence After Therapy. J Infect Dis. 2012;206:357-365.
Darville T, et al. Pathogenesis of genital tract disease due to Chlamydia trachomatis. J Infect Dis. 2010 Jun 15;201 Sppl 2:S114-25.
Mehta SD, Moses S, et al. Adult Male Circumcision Does Not Reduce the Risk of Incident Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis Infection: Results from a Randomized, Controlled Trial in Kenya. J Infect Dis. 2009 Aug 1;200:370-378.
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