Mycoplasma Infections Part 2

Specific Laboratory Testing

Laboratory diagnosis of an acute M. pneumoniae infection can be established (1) by the isolation of M. pneumoniae from respiratory tract secretions (oropharyngeal, nasopharyngeal, or pulmonary) with PCR or culture (which requires special media) or (2) by the use of specific serologic tests, such as complement fixation, indirect immunofluorescence, and enzyme immunoassays (EIAs) for specific IgM and IgG antibodies in paired (acute and convalescent) serum samples [see Table 1]. Of these methods, EIAs are the most widely used and the most adaptable to the clinical laboratory setting.79 Serum samples for M. pneumoniae serology taken only during the acute phase of illness may not be indicative of infection, because antibodies to M. pneumoniae may not develop for 2 weeks or more; therefore, it is important to test both acute and convalescent serum samples for accurate diagnosis. IgM antibodies against M. pneumoniae may not be produced during reinfection in older patients (i.e., persons older than 40 years with preexisting anti-M. pneumoniae IgG antibodies).80 In addition, specific IgM can persist for up to a year after acute M. pneumoniae infection and so may indicate recent infection rather than acute infection.

M. pneumoniae culture is not recommended for routine diagnosis, because the organism may take weeks to grow and is of ten difficult to isolate from clinical specimens, so sensitivity is low. PCR allows a rapid and specific diagnosis to be made early in the course of clinical illness. The combination of respiratory tract PCR testing and EIA has been recommended as the most sensitive and rapid approach to the diagnosis of M. pneumoniae infection.81 In children, PCR assays of nasopharyngeal or oropha-ryngeal samples appear equally effective for the diagnosis of serologically confirmed M. pneumoniae pneumonia; however, testing of specimens from both sites is optimal.82


Treatment

Because the clinical manifestations of Mycoplasma pneumonia are not distinctive and laboratory diagnosis is often made retrospectively, treatment is usually empirical, as it is with community-acquired pneumonia in general. The possibility of M. pneumoniae infection deserves particular consideration in a patient with community-acquired pneumonia who has failed to respond to treatment with a penicillin or a cephalosporin, because ^-lactam antibiotics are ineffective against mycoplasmas. Clinical trials ranging from observational reports to randomized, double-blind, placebo-controlled studies have demonstrated that appropriate antimicrobial therapy significantly decreases the duration of fever, cough, malaise, hospitalization, and radiologic abnormalities in Mycoplas-ma pneumonia.53 In one study of military trainees with serological-ly confirmed M. pneumoniae pneumonia, treatment with oral ery-thromycin for 7 days reduced mean duration of fever from 4.2 days to 2.4 days; the duration of hospitalization was reduced from 14.1 days to 7.0 days; and the period in which radiologic abnormalities were present was reduced from 14.8 days to 7.2 days.83

Treatment options for acute M. pneumoniae infection include macrolides, ketolides, tetracyclines, and most fluoroquinolones (ciprofloxacin and ofloxacin are not recommended because of their high minimum inhibitory concentrations and poor performance in animal studies) [see Table 2]. Antimicrobial resistance has not been clinically important in M. pneumoniae infections in North America. The optimal antibiotic choice, dosage, and duration are not clear; however, 14 days of therapy is generally recommended.


Even after therapy with appropriate antibiotics, M. pneumoni-ae can still be cultured from respiratory tract secretions.8,84 The persistence of M. pneumoniae in the nasopharynx of children after clarithromycin therapy (given for an acute exacerbation of wheezing accompanying M. pneumoniae infection) has been associated with recurrent wheezing.85 In animal models of My-coplasma pneumonia, treatment with antimycoplasmal agents such as ketolides, quinolones, clarithromycin, and azithromycin also has not eradicated this organism from the respiratory tract.55 The efficacy of combination antimicrobial therapy for the eradication of M. pneumoniae has not been investigated.

Table 1 Accuracy of Diagnostic Tests for Mycoplasma pneumoniae Infection

Test

Sensitivity

(%)

Specificity

(%)

Comment

Culture*

s 60

100

Not recommended for clinical diagnosis

Polymerase chain reaction (PCR)*

65-90

90-100

Combination of PCR and enzyme immunoassays (EIAs) is optimal for diagnosis

Serologic studies

55-100

55-100

EIAs for M. pneumoniae IgM and IgG in paired (acute and convalescent) serum samples is the recommended serologic method

*Using respiratory tract secretions.

Table 2 Antimicrobial Treatment of Mycoplasma Infections  

Pathogen

Infection

Representative Drugs*

Mycoplasma pneumoniae

Respiratory tract infection

Macrolides: azithromycin, clarithromycin, erythromycin

Ketolides: telithromycin

Tetracyclines: doxycycline

Fluoroquinolones1; levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin

Ureaplasma urealyticum

Doxycycline*

Nongonococcal urethritis

Azithromycin

Alternatives: erythromycin base, levofloxacin

M. genitalium

Nongonococcal urethritis, pelvic inflammatory disease

Azithromycin

M. hominis

Pelvic inflammatory disease; persistent postabortion or postpartum fever; acute pyelonephritis

Doxycycline

Clindamycin

*The optimal antibiotic choice for Mycoplasma infection is not clear, and a variety of dosages and treatment durations are used; however, the typical duration of M. pneumoniae treatment is 14 days. Ciprofloxacin and ofloxacin are not recommended.

*U. urealyticum strains that are resistant to tetracyclines are usually sensitive to macrolides or quinolones.

In both animal and human studies, antimycoplasmal therapy significantly alleviated chronic respiratory disease caused by M. pneumoniae.86,87 A randomized, double-blind, placebo-controlled trial in patients with stable chronic asthma showed that 6 weeks of treatment with clarithromycin produced significant improvement on respiratory function testing in those patients who tested positive for M. pneumoniae by PCR but not in those who tested negative; control subjects who received placebo also showed no improvement.87 Additional clinical studies are needed to strengthen this observation.

Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum

Because mycoplasmas and ureaplasmas often colonize the lower genitourinary tract of healthy adults (especially those who are sexually active), positive cultures for these organisms do not necessarily constitute proof of infection. Despite this difficulty, there is evidence that M. hominis, M. genitalium, and U. ure-alyticum can cause several clinical syndromes.3,88 The significance of isolating these organisms in a variety of other syndromes is in-vestigational or unknown.

Nongonococcal urethritis

About 40% of men who experience an initial episode of non-gonococcal urethritis have infection caused by C. trachomatis [see 7:XIII Diseases Due to Chlamydiaj.89 In many cases of Chlamydia-negative nongonococcal urethritis (negative culture and negative serology), U. urealyticum may be the causative agent, as judged by (1) the presence of larger numbers of U. urealyticum organisms in Chlamydia-negative cases than in Chlamydia-posi-tive cases; (2) the production of urethritis in human volunteers and nonhuman primates by intraurethral inoculation of U. ure-alyticum clinical isolates; and (3) the differential response to sul-fisoxazole therapy (in one study, all 13 patients with Chlamydia-positive, Ureaplasma-negative nongonococcal urethritis showed a response, compared with only 14 of 30 Chlamydia-negative, Ureaplasma-positive patients).89 C. trachomatis is susceptible to sulfonamides, but U. urealyticum is not. Such evidence suggests that U. urealyticum is the cause of at least some initial episodes of Chlamydia-negative nongonococcal urethritis in men—perhaps as many as 15% to 25% of these episodes.90 Other studies have implicated U. urealyticum as a cause of acute urethral syndrome in some women; this organism may also cause chronic voiding symptoms in women, which may be mistaken for interstitial cys-titis.91 It is possible that factors such as serotype, strain-specific virulence determinants, or host factors will explain why positive cultures for U. urealyticum are not better correlated with evidence of clinical infection. Alternatively, disease may develop only upon initial exposure to ureaplasmas. U. urealyticum also has been implicated in urethroprostatitis and epididymitis.3

M. genitalium also appears to cause acute and possibly chronic nongonococcal urethritis.88,92 One group of investigators found M. genitalium DNA in C. trachomatis-negative samples from 22% of heterosexual men with nongonococcal urethritis but from only 4% of asymptomatic control subjects.93 Other studies have confirmed the disproportionate detection rates of M. genitalium in patients with nongonococcal urethritis. M. genitalium does not have a known role in prostatitis or epididymitis.88 M. hominis does not appear to have a primary etiologic role in nongonococcal urethritis.

Treatment

Doxycycline (100 mg orally two times daily for 7 days) or azithromycin (1 g orally as a single dose) is the recommended treatment for nongonococcal urethritis. Erythromycin base (500 mg orally four times daily for 7 days) or levofloxacin (500 mg once daily for 7 days) are alternatives. These treatment regimens apply to cases associated with U. urealyticum as well as M. geni-talium.94 Tetracycline resistance has increased in recent decades and has been reported in as many as one third of clinical U. ure-alyticum isolates.95 Resistant strains are known to cause persistent urethritis that often does not respond to treatment with tetracy-clines; however, they are usually sensitive to macrolides or quinolones.96 Sexual contacts of an index case should be treated at the same time as the index case. Other causes of treatment failure include poor compliance with medications, reinfection, disease caused by Trichomonas vaginalis or herpes simplex virus, prostatitis, and noninfectious etiologies.

For M. genitalium, the treatment of choice seems to be azithromycin. Treatment failures have been reported with other macrolides and with quinolones.

Upper urinary tract infection

M. hominis causes approximately 5% of acute pyelonephritis cases, judging from culture and serologic data.97 However, the same association cannot be made for U. urealyticum.3 Treatment of acute pyelonephritis from M. hominis is the same as that for pelvic inflammatory disease (PID) from this organism (see below).

U. urealyticum has a limited role in the production of urinary calculi. The frequency with which U. urealyticum reaches the kidney, the predisposing factors that allow this to occur, and the relative frequency of renal calculi induced by this organism as compared with other organisms is not known.3

Pelvic inflammatory disease

M. hominis may cause some episodes of PID. In most of these cases, the organism occurs as part of a polymicrobial infection, but isolation of M. hominis from laparoscopic cultures of fallopian tubes in women with acute salpingitis has been reported, and the organism may be responsible for a few cases of PID on its own.98 The prevalence of M. hominis involvement in PID may vary with global geographic location. It remains unclear how large a role M. hominis plays in the development of acute salpin-gitis and its sequelae. Some data also exist for an association of M. genitalium with PID.88 In contrast, U. urealyticum is not considered to be a cause of PID.3

Treatment

M. hominis is resistant to the macrolides. Doxycycline is generally the drug of choice for M. hominis infections, although resistance has been reported.99 Clindamycin is also generally active against M. hominis. Quinolones and ketolides have been found to be active in vitro against M. hominis; however, clinical experience is lacking.96,100

Postabortion and postpartum fever

Positive blood cultures and concurrent seroconversion have implicated M. hominis as the primary pathogen in approximately 10% of women who have fever after abortion.3 M. hominis is also responsible for 5% to 10% of fevers that arise more than 24 hours after vaginal delivery.101 Women with vaginal colonization by M. hominis who have low or absent antibody titers against Mycoplas-ma may be predisposed to postpartum fever, which is probably associated with endometritis. These infections are usually self-limited; if symptoms persist, however, specific antimicrobial therapy should be given as for M. hominis PID (see above).

Other conditions associated with mycoplasmas

M. hominis rarely causes brain abscess, wound infection, post-sternotomy mediastinitis,102 neonatal meningitis, and other non-genitourinary infections.103,104 These infections are more common in immunocompromised or hypogammaglobulinemic persons. U. urealyticum and M. hominis can cause septic arthritis in im-munodeficient patients,3 and U. urealyticum likely causes neonatal pneumonitis and contributes to neonatal chronic lung disease (including bronchopulmonary dysplasia).105 It is unclear whether U. urealyticum and M. hominis can cause male and female infertil-ity,106 spontaneous abortion,107 premature labor and low birth weight,108 and chorioamnionitis.

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