INFECTIOUS DISEASES
Educational Objectives
| The goals of this program are to reduce transmission of sexually transmitted diseases (STDs) and to improve management
of tuberculosis (TB). After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Implement evidence-based recommendations for screening men and women for STDs.
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| 2. Diagnose and treat patients with STDs.
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| 3. Educate patients about risk, risk reduction, and the prevention of transmission of STDs.
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| 4. Identify pitfalls in the management of TB.
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| 5. Adequately treat patients with multidrug-resistant TB.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgments
Dr. Adler was recorded at Annual Review in Family Medicine—Controversies and Challenges in Primary Care, presented
by Department of Family and Community Medicine, University of California, San Francisco, School of Medicine,
and held April 6-8, 2008, in San Francisco; Dr. Asmuth was recorded at 26th Annual Infectious Disease
Conference, presented by University of California, Davis, School of Medicine, and held January 25-26, 2008, in Sacramento.
The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production
of this program.
| SEXUALLY TRANSMITTED DISEASES —Sharon Adler MD, MPH, Clinical Instructor, California STD/HIV Prevention
Training Center, and California Department of Public Health, STD Control Branch, Oakland, CA
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| Sexual history: new guidelines by Centers for Disease Control and Prevention (CDC) recommend that sexual history be
part of routine visits to primary care provider; counseling patients about risk and risk reduction associated with lower incidence
of sexually transmitted diseases (STDs), including HIV
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| General prevention: condoms—when used correctly and consistently, reduce transmission of many STDs; data show
use of nonoxynol-9 associated with disruption of vaginal epithelium and increased risk for HIV and urinary tract infections;
women who have sex with women (WSW)—added as special population; STDs of concern include trichomoniasis,
bacterial vaginosis (BV), human papillomavirus (HPV), and HIV; sharing sex toys may increase transmission of chlamydia
and gonorrhea
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| Screening women: the following screening is recommended for all sexually active women ≤25 yr of age; chlamydia and
gonorrhea—routine annual screening; other STDs—screening based on risk (eg, multiple partners; history of STD; inconsistent
use of barrier contraception); ≥1 HIV test recommended for most patients during lifetime, regardless of risk;
women \>25 yr of age—screening based on risk; because of high prevalence of gonorrhea among black women ≤30 yr of
age in California, screening recommended for this population; pregnant women—consider screening for BV for women
with history of preterm delivery or premature rupture of membranes (some data suggest, however, that treating asymptomatic
women does not change outcomes)
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| Screening men: routine screening not recommended for heterosexual men (does not reduce risk for serious sequelae
among female partners); selective screening recommended in high-prevalence populations (eg, adolescent clinics, corrections
facilities, job corps settings); local prevalence ≥6% warrants screening
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| Men who have sex with men (MSM): routine annual screening for HIV, syphilis, and urethral gonorrhea and chlamydia (anal
and pharyngeal screening based on risk factors); no consensus about screening for herpes simplex virus type 2 (HSV-2);
anal Papanicolaou (Pap) test not recommended by CDC (but some experts recommend); shorter screening intervals—
consider screening every 3 to 6 mo for high-risk individuals; importance of rectal and pharyngeal screening—urine and
urethral screening misses ≈50% of chlamydial and gonorrhea infections among men with risk factors
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| Diagnostic tests: nucleic acid amplification tests (NAATs) recommended; advantages of NAATs—higher sensitivity (detect
40% more chlamydial infections); less dependent on collection and handling techniques; noninvasive (self-collected
urine samples or vaginal swabs sufficient); useful in clinical and nonclinical settings; limitations of NAATs—not approved
for rectal or pharyngeal specimens; laboratory verification study required before using NAAT to screen rectal or
pharyngeal specimens for Chlamydia; cultures—samples from pharynx or rectum acceptable for gonorrhea screening
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| Treatment of gonorrhea: fluoroquinolones no longer recommended because of high rates of resistance; recommended
regimens—ceftriaxone, 125 mg intramuscularly (IM; preferred) or cefixime orally; azithromycin (2 g) alternative for pharyngeal
infections; alternatives for patients allergic to penicillin or cephalosporins—spectinomycin; azithromycin (but,
concerns about resistance); desensitization (limited utility); when using azithromycin, test of cure required (culture at 1
wk, or NAAT at 3-4 wk)
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| Patient-delivered partner treatment (PDPT): also known as expedited partner treatment; partners of infected patients
treated without evaluation; clinical evaluation always recommended when possible; studies show PDPT reduces rates
of reinfection among heterosexual couples and WSW; not recommended for MSM because of high rate of comorbid STDs,
including HIV; requires—appropriate prescription or medications for partner; information about contraindications to medical
therapy; information (for women) about pelvic inflammatory disease (PID); Expedited Partner Therapy Trial—PDPT
resulted in 73% reduction in reinfection with gonorrhea and ≈15% reduction in reinfection with chlamydia, compared to
standard approach; legality—determined by state (see CDC Web site: www.cdc.gov/std/ept/legal/default.htm)
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| Retesting: 15% to 20% of men and women reinfected within 3 to 4 mo of initial treatment; consider retesting at 3 mo for
patients with gonorrhea or chlamydia; if patient does not return at 3 mo, retest within 12 mo of initial treatment; test of
cure—recommended at 3 to 4 wk after treatment of chlamydia in pregnant women and after treatment of gonorrhea with
azithromycin
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| Herpes testing: type-specific glycoprotein G serology tests distinguish between HSV-1 and HSV-2 (other tests do not);
indications—patient with recurrent or atypical symptoms (eg, “recurrent vaginitis” without evidence of yeast or trichomoniasis);
previous clinical diagnosis without laboratory confirmation; partner infected with HSV; patient who requests
testing as part of comprehensive evaluation for STDs; patients at high risk; HIV-infected patients (in California, all
HIV-infected patients screened for HSV; herpes outbreak may increase transmission of HIV and HSV); screening general
population—not recommended
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| Herpes treatment: episodic treatment for recurrence—3 recommended regimens; acyclovir, 200 mg orally 5 times daily
no longer recommended, due to poor compliance; prevention of transmission—daily suppressive therapy with 500 mg valacy
clovir decreases transmission by 50% in discordant heterosexual couples; indications include discordant heterosexual
couples, individuals with multiple partners, asymptomatic patients seropositive for HSV-2 (patients unaware of viral shedding
have high rate of transmission), and HIV-positive patients
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| Recommendation highlights for syphilis: enzyme immunoassay (EIA) tests available; mainstay of treatment remains
penicillin G benzathine, 2.4 million U; azithromycin discouraged (removed as option in California); penicillin issues—
Bicillin C-R (combined release) contains penicillin G procaine and penicillin G benzathine and is inadequate for treating patients
with syphilis (use penicillin G benzathine IM [eg, Bicillin L-A] only)
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| Syphilis testing: EIA tests approved for clinical use; tests appropriate for screening, but positive results require follow-
up with rapid plasma reagin (RPR) test or VDRL for quantitative titer (important for management); advantages—low
cost; automated; no prozone problems; disadvantages—limited guidance about interpreting results; absence of data
about sensitivity and specificity, compared to Treponema pallidum hemagglutination assay (TPHA) tests
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| Syphilis treatment: recommended regimen—penicillin G benzathine preferred for all adults and only recommended
agent for pregnant women; alternatives—for nonpregnant patients allergic to penicillin include doxycycline, tetracycline,
and ceftriaxone; azithromycin discouraged
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| Diagnosis of cervicitis: Mycoplasma genitalium recognized as etiologic agent (may account for cases that respond to
treatment but negative for gonorrhea and Chlamydia); diagnostic criteria—presence of endocervical mucopus or cervical
friability; \>10 white blood cells (WBCs) present on vaginal wet mount (absence of WBCs has good negative predictive
value); additional evaluation for women with cervicitis—PID; BV; Trichomonas; gonorrhea and chlamydia
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| Treatment for cervicitis: chlamydia—treat empirically in sexually active women ≤25 yr of age, women at high risk for
STDs, and those unlikely to follow up; gonorrhea—decision to treat empirically based on individual risk and local prevalence
(treat when \>5%); BV—always evaluate; treat if present
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| Pelvic inflammatory disease (PID): etiologic agent—M genitalium; diagnostic criteria—cervical motion tenderness,
uterine tenderness, or adnexal tenderness; diagnosis unlikely among women without cervicitis and without WBCs on wet
mount
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| Treatment for PID: avoid fluoroquinolones; first-line treatment—ceftriaxone, cefoxitin with probenecid, or other third-
generation cephalosporin plus doxycycline; metronidazole added if evidence of BV; penicillin allergy—desensitization
required if gonorrhea present (fluoroquinolones inadequate)
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| Point-of-care tests: OSOM Trichomonas Rapid Test (Genzyme)—rapid test with good sensitivity; Affirm VPIII Microbial
Identification Test (BD Diagnostics)—for diagnosis of trichomoniasis, BV, and yeast; requires ≈45 min, but has good sensitivity
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| Trichomoniasis: diagnosis—culture remains gold standard; treatment—tinidazole has fewer adverse effects than metronidazole;
metronidazole resistance occurs in 2% to 5% of women treated for vaginal trichomoniasis; pregnancy—
limited data suggest metronidazole may increase risk for preterm labor and low birth weight babies; consider withholding
treatment until 37 wk of pregnancy (weigh against risks associated with delayed treatment); lactation—discontinue
breast-feeding until 24 hr after last dose of metronidazole and 3 days after last dose of tinidazole; treatment failure—after
first failure, retreat with 500 mg metronidazole (bid for 7 days) or 2 g tinidazole; after second failure (and reinfection
from untreated partner ruled out), increase dose to 2 g metronidazole or tinidazole for 5 days; susceptibility testing recommended
if patient returns with third treatment failure
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| Bacterial vaginosis: “sexually associated” but treatment of male partners does not decrease recurrence rates in women;
changes in treatment recommendations—metronidazole, 500 mg orally bid for 7 days, preferred; single dose of metronidazole
(2 g) no longer recommended (poor efficacy); metronidazole, 500 mg orally bid for 7 days, added as option for pregnant
women; suppressive therapy—after therapeutic regimen completed, patient applies metronidazole gel twice weekly
for 6 mo
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| Indications for HPV DNA testing: triage of atypical squamous cells of undetermined significance (ASCUS); adjunct
screening (with Pap test) for women ≥30 yr of age; inappropriate for use among younger women
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| NEW CHALLENGES IN TUBERCULOSIS —David Asmuth, MD, Associate Professor, Division of Infectious Diseases,
Department of Internal Medicine, University of California, Davis, Health System, Sacramento
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| Definitions: multidrug-resistant (MDR) tuberculosis (TB)—isolate resistant to isoniazid and rifampin; extensively drug-
resistant (XDR) TB—isolate also resistant to fluoroquinolone and ≥1 injectable drug; primary resistance—resistance exists
at time of infection; secondary resistance—resistance develops during treatment
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| Distribution: prevalence very high in some regions (eg, former Soviet Union); United States—<6% of recurrent cases
MDR TB (decreasing among US-born individuals); most cases of primary XDR TB occur in New York City and California
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| Case: homeless man, 60 yr of age, has positive tuberculin skin test and abnormal chest radiograph, characterized by emphysema
and scarring of right upper lobe; sputum positive for acid-fast bacilli (AFB); culture grows pansensitive Mycobacterium
tuberculosis; treatment—self-administered isoniazid and rifampin initiated; patient not adherent; ≈6 mo later, sputum
remains positive for AFB; ethambutol added to therapy; ≈10 mo later, problems with adherence and alcohol abuse persist;
chest radiograph shows no change; sputum remains positive; isoniazid and rifampin discontinued because of elevated liver
enzymes; isoniazid reinitiated and pyrazinamide and streptomycin added to regimen (note, addition of pyrazinamide inappropriate,
due to elevated liver enzymes); ≈4 mo later, patient lost to follow-up; ≈1 yr later, patient presents to emergency
department with cough; self-administration of treatment reinitiated; ≈9 mo later, patient again lost to follow-up
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| Principles of care: barriers to adherence—must be assessed and addressed; nonadherent patients should receive directly
observed therapy (DOT); resistance—treatment failure is red flag; susceptibility studies recommended when cultures
remain positive after treatment; medical regimen—insufficient to add single drug to failing regimen; instead, add 2
to 3 new drugs with proven or suspected efficacy
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| Case continued: 10 yr later—patient discharged from local hospital with diagnosis of pulmonary TB; chest radiograph
abnormal, and sputum positive for AFB; patient provides history of nonadherence to previous treatment; retreatment
regimen—DOT with isoniazid, rifampin, pyrazinamide, and ethambutol initiated while waiting for results of susceptibility
test; test results show resistance to isoniazid, rifampin, kanamycin, amikacin, ciprofloxacin, and ethionamide; although patient
appeared responsive to treatment, regimen revised (isoniazid and rifampin discontinued; streptomycin, ofloxacin,
and clofazimine added); 5 mo later, ofloxacin dose increased, then streptomycin discontinued; 5 mo later, treatment considered
adequate and discontinued; 5 days later, laboratory reported recent sputum sample positive for AFB
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| Management: appropriate decisions—previous poor adherence recognized and addressed; risk for drug resistance identified,
but treatment regimen not sufficiently expanded; treatment regimen changed in response to susceptibility report;
errors in management—revised therapy included 3 drugs used previously in failed therapy; ethambutol and pyrazinamide
used alone; ofloxacin poor choice due to ciprofloxacin resistance; clofazimine poor choice (unknown efficacy); although
12 mo of injectable therapy after culture conversion often sufficient, duration depends on disease severity and resistance;
2 yr of treatment after culture conversion typically recommended (ie, treatment discontinued prematurely)
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| Treatment algorithm: step 1—begin with first-line agents with demonstrated efficacy; add fluoroquinolone and injectable
drug based on susceptibility; step 2—add second-line drugs; use 4 to 6 drugs with demonstrated efficacy; step 3—if
sufficient numbers of first- and second-line drugs not available (ie, isolate highly resistant), consider third-line drugs (imipenem-cilastatin;
linezolid; macrolides; amoxicillin/clavulanate)
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| Other management issues: repeat cultures monthly to monitor response of MDR TB to therapy; repeat drug susceptibility
test when cultures remain positive for 3 mo; specify extended susceptibility test for patients with MDR TB; consult
expert; initiate therapy with sufficient numbers of oral medications to ensure adequate regimen once injectable agent discontinued;
do not limit regimen to 3 agents if others indicated; avoid intermittent therapy; avoid drugs to which resistance
demonstrated (even if patient responding); monitor serum levels of drugs (especially bactericidal or toxic drugs); note,
isolates resistant to rifampin also usually resistant to rifabutin and always resistant to rifapentine
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| Following and treating contacts: guidelines recommend following contacts of patients with MDR TB for ≥2 yr (but
data on management limited); regimens usually consist of pyrazinamide with quinolone or ethambutol, but tolerance low,
compared to that for isoniazid
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| Blood assays for M tuberculosis: for diagnosis of latent TB infection; protocol—blood sample incubated overnight
with antigens specific for M tuberculosis; if latent infection present, lymphocytes react by releasing interferon-γ enzyme-linked
immunosorbent assay (ELISA) quantitates response; benefits over skin test—requires only one visit; does
not boost previous response; interpretation less subjective; not affected by bacillus Calmette-Guérin (BCG) vaccination;
disadvantages—more expensive; untested in some populations, including children
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Suggested Reading
Bauer HM et al: California guidelines for expedited partner therapy for Chlamydia trachomatis and Neisseria gonorrhoeae
. Sex Transm Dis Dec 28, 2007 [Epub ahead of print]; Blake DR et al: Cost-effectiveness of screening strategies
for Chlamydia trachomatis using cervical swabs, urine, and self-obtained vaginal swabs in a sexually transmitted disease
clinic setting. Sex Transm Dis May 5, 2008 [Epub ahead of print]; Cox HS et al: Long term efficacy of DOTS regimens
for tuberculosis: systematic review. BMJ 336:484, 2008; Dover LG et al: new drugs and vaccines for drug-resistant Mycobacterium
tuberculosis infections. Expert Rev Vaccines 7:481, 2008; Frank MF et al: Risk factors and mortality associated
with default from multidrug-resistant tuberculosis treatment. Clin Infect Dis May 5, 2008 [Epub ahead of print];
Kennedy SB et al: Urban African-American males’ perceptions of condom use, gender and power, and HIV/STD prevention
program. J Natl Med Assoc 99:1395, 2007; Markowitz LE et al: Quadrivalent human papillomavirus vaccine:
recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 56(RR-2):1, 2007; Mimiaga
MJ et al: Asymptomatic gonorrhea and chlamydial infections detected by nucleic acid amplification tests among
Boston area men who have sex with men. Sex Transm Dis 35:495, 2008; Nadol P et al: Electronic tuberculosis surveillance
systems: a tool for managing today’s TB programs. Int J Tuberc Lung Dis 12(3 Suppl 1):8, 2008; Romanowski B
et al: In search of optimal genital herpes management and standard of care (INSIGHTS): doctors’ and patients’ perceptions
of genital herpes. Sex Transm Infect 84:51, 2008; Tao G, Irwin KL: Receipt of HIV and STD testing services during
routine general medical or gynecological examinations: variations by patient sexual risk behaviors. Sex Transm Dis
35:167, 2008; Williams JR et al: Suppressive valacyclovir therapy: impact on the population spread of HSV-2 infection.
Sex Transm Dis 34:123, 2007; Yew WW et al: Linezolid in the treatment of “difficult” multidrug-resistant tuberculosis.
Int J Tuberc Lung Dis 12:345, 2008.
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