Infectious Disease Update

Educational Objectives

The goal of this program is to decrease complications associated with transmissible infections. After hearing and as­similating this program, the clinician will be better able to:

1.   Implement screening recommendations for Chlamydia, gonorrhea, herpes simplex virus (HSV) and human papillomavirus (HPV).

2.   Diagnose and treat women with common sexually transmitted infections (STIs).

3.   Discuss the value of the HPV vaccine for appropriate candidates.

4.   Detail the risk factors for community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), and compare CA-MRSA to hospital-associated isolates.

5.   Prevent the transmission and recurrence of MRSA infections by appropriate management, decolonization, and patient education.

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. Dr. Mejicano presents information about off-label use of therapies related to decolonization of MRSA.

Acknowledgments

Dr. Bauer was recorded at Primary Care Medicine: Principles and Practice, presented by the University of California, San Francisco, School of Medicine, and held October 29-31, 2008, in San Francisco; Dr. Mejicano was recorded at the 2008 Pri­mary Care Conference, jointly presented by University of Wisconsin School of Medicine and Public Health and University of Wisconsin, Madison, Continuing Education in Nursing, and held November 13-14, 2008, in Madison. The Audio-Digest Foun­dation thanks the speakers and the sponsors for their cooperation in the production of this program.

Sexually Transmitted Infections in Women

Heidi M. Bauer, MD, MPH, Chief, Program Development and Evaluation, STD Control Branch, California Department of Public Health, Richmond

Risk factors: young age; ethnicity; sex (higher in women); some regional differences; sexual history and number of partners; absence of barrier control; age  —  study by Centers for Disease Control and Prevention (CDC) found 1 in 4 teenaged girls has sexually transmitted infection (STI); rates higher in some populations (eg, sexually active teens, blacks); anatomic and physiologic factors  —  women have larger mucosal surface and prolonged exposure to secretions (compared to men); cervical ectopy (predominance of columnar epithelium [susceptible to Chlamydia]), thin cervical mucus, and naive immune system increase risk in young women; sociocultural issues  —  power differ­entials within relationships; differential behavioral norms; limited options for female-controlled barrier methods; shame and stigma; access to information about sexuality; health care access (eg, financial barriers; challenges to partner treatment)

Complications: STIs often asymptomatic in women; absence of symptoms leads to delay in seeking care and in­creased risk for complications; upper genitourinary tract infections with Chlamydia or gonorrhea may lead to infer­tility, ectopic pregnancy, or chronic pelvic pain; STIs increase risk of contracting HIV if exposed; pregnancy and neonatal complications; cancer (eg, related to infection with human papillomavirus [HPV] and hepatitis B virus); systemic infection and chronic disease (eg, syphilis)

General guidelines for screening: sexually active girls and women £25 yr of age  —  annual screening for Chlamydia trachomatis and Neisseria gonorrhoeae; Papanicolaou (Pap) test 3 yr after sexual debut; screening for other STIs and HIV based on risk; women >25 yr of age  —  lower risk; screening based on individual risk factors; pregnant women  —  many screening tests recommended

Chlamydia (CT) and Gonorrhea (GC)

Trends: substantial increases in (recognized) incidence of CT (among men and women), largely due to improved di­agnostic tests and increased rates of screening; incidence of GC has decreased since 1970s (with slight increase in recent years); rates similar for men and women; ethnic disparities  —  black and Hispanic women have high rates (eg, 19-fold higher rates of GC, compared to white women)

Screening for CT: recommendations  —  all sexually active girls and women £25 yr of age; pregnant women; men who have sex with men (MSM); others according to risk (eg, new or multiple sexual partners, partner with other sexual partners, history of CT, current infection with other STIs, or high-prevalence setting); screening rates have improved nationally, but remain under goal; nucleic acid amplification tests (NAATs)  —3 tests currently available; all highly sensitive; noninvasive collection of specimens (eg, self-collected urine or vaginal swabs) acceptable; pel­vic examination not required

Screening for GC: less data about cost-effectiveness and impact on outcomes; current recommendations mirror those for CT; NAATs test single sample for GC and CT

Managing uncomplicated GC: intramuscular (IM) injection of ceftriaxone highly effective, but oral drugs preferred in many settings; oral regimens  —  cephalosporins recommended (eg, cefixime; note, oral cephalosporins less effec­tive for managing pharyngeal gonorrhea); fluoroquinolones used less frequently, due to resistance (still suitable in areas with low rates of resistance); azithromycin effective, but some limitations to use (considered alternative op­tion); recommendations  —  avoid fluoroquinolones; give 125 mg IM ceftriaxone (single dose) or oral cefixime; also treat for CT (»50% of individuals coinfected) with azithromycin or doxycycline

Expedited partner treatment (EPT): providing medication (or prescription) for partners of infected patients; study  —  patients randomized to EPT or usual care; EPT associated with reduced rates of reinfection with N gonor­rhoeae (reduced from 10.6% to 3.4%) and C trachomatis (nonsignificant trend; meta-analysis found »20% de­crease); decrease in reinfection rate may translate to fewer complications; CDC recommendations  —  website (www.cdc.gov/std/ept), excellent source of information; EPT considered safe and effective for reducing rates of re­infection with C trachomatis and N gonorrhoeae, but clinical evaluation preferred; some concern about missed op­portunities for counseling; legal issues  —  EPT legal in California; more states enacting legislation that allows EPT (see CDC website for updates)

Retesting: high rates of reinfection (15%-20% at 3-6 mo after treatment); recommendations  —  retest at 3 mo after treatment; expedited visit acceptable

Genital Herpes

Epidemiology: almost 25% of adults in United States infected with herpes simplex virus type 2 (HSV-2); most have no history of outbreaks but have positive serology and capable of transmitting virus

Screening: rationale  —  80% of infected individuals unaware of infection (and risk for transmission); patients may be taught to recognize symptoms (including atypical symptoms), seek treatment as needed, and/or avoid sexual con­tact; awareness of infection may decrease risky sexual behavior and/or increase disclosure to partners; suppressive treatment decreases transmission; type-specific serologic tests  —  all have good performance characteristics; some identify HSV-1 and HSV-2 (testing for HSV-1 has questionable clinical value, because most individuals seroposi­tive); CDC guidelines suggest use for patients with recurrent genital symptoms or atypical symptoms with negative culture for HSV, patients with history of clinical diagnosis without laboratory confirmation, and patients with sero­positive partners; some suggest inclusion in comprehensive STI evaluation for patients with multiple sexual part­ners or HIV and for MSM at risk for HIV infection (conflicting evidence regarding benefit)

Suppressive treatment: daily treatment in asymptomatic patients; uses  —  episodic use to prevent outbreaks during defined time periods (eg, special occasions); patients with frequent severe outbreaks (³6 per yr); to decrease risk for transmission; during pregnancy (near term); CDC recommendations  — use in discordant heterosexual couples en­couraged; consider use in individuals with multiple sexual partners (including MSM) and in seropositive patients without history of genital herpes; counsel patients about condom use, disclosure, and abstinence during outbreaks; study  —  suppressive treatment decreased transmission rate in discordant heterosexual partners from 3.6% to 1.9% (during 8-mo period); reduction in risk similar to that associated with consistent use of condoms (»50%; encour­aged in addition to suppressive therapy)

Human Papillomavirus

Epidemiology: virtually all men and women infected with genital HPV during sexual lifetime; most young women infected within few years of sexual debut; 90% of infections resolve spontaneously within »2 yr; low-grade and some high-grade disease may regress spontaneously

Testing: Digene HPV tests (Qiagen)  —  test for high-risk types (testing for low-risk types has limited clinical utility); probes recognize 13 high-risk types of HPV, but specific type not identified (positive or negative result only); use  —recommended for triage of women with atypical squamous cells of undetermined significance (ASCUS) on Pap test and for screening (in combination with Pap test) in women ³30 yr of age; other recommended uses detailed in guidelines; inappropriate for  —  screening women <30 yr of age; diagnosing warts; testing in men; diagnosing high-grade lesions; screening patients before or after vaccine; screening patients with STIs (or their partners)

Vaccine: based on L1 capsid protein; Gardasil (Merck) covers HPV types 6 and 11 (»90% of genital warts) as well as 16 and 18 (»70% of cervical cancer); 3-dose series (0, 2, and 6 mo); similar vaccines in development; HPV types  —  type 16 responsible for >50% of cervical cancers worldwide; type 18 responsible for »18%; other high-risk types responsible for small proportion of disease burden; efficacy  —  highly effective at preventing high-grade disease (cervical, vulvar, and vaginal) in women with no history of exposure to HPV; efficacy decreases with infection with HPV types covered by vaccine (ie, prophylactic, not therapeutic); protective effect lasts ³5 yr (antibody level de­creases <5% each year); need for booster unknown at this time; safe and immunogenic in males (efficacy data forthcoming); adverse reactions  —  pain, swelling, itching, and redness at injection site; fever, nausea or dizziness may occur; patients should remain seated for 15 min in case of dizziness or fainting; guidelines  —  routine vaccina­tion for girls, 11 to 12 yr of age; catch-up vaccination in young women up to 26 yr of age; acceptable to vaccinate, even if Pap test shows abnormal cytology; contraindicated during pregnancy (continue series after pregnancy); guidelines list contraindications; vaccination does not alter need for cervical cancer screening

Questions and Answers

HSV testing: cross-reactivity between HSV-1 and HSV-2  —  high level of HSV-1 antibodies may appear as “low-pos­itive” for HSV-2; before notifying patient, check HSV-1 antibody level (if low, test results represent true positive); testing after recent exposure  —  seroconversion requires ³3 wk; 90% of patients seroconvert by 3 mo; earlier testing can measure baseline level of antibodies (eg, from previous exposure); serology likely to be negative in patient with primary infection

STIs in men: sample collection for CT and GC  —  NAAT results using urine samples highly sensitive and specific; no screening recommendations for heterosexual men; HPV testing  — ongoing research on specimen collection; men have similar rates of infection and regression as women; no treatment or testing recommendations for asymptom­atic men

Community-Acquired MRSA: Risks and Management

George C. Mejicano, MD, Associate Professor of Medicine, Section of Infectious Diseases, and Associate Dean for Continuing Professional Development, University of Wisconsin School of Medicine and Public Health, Mad­ison

Clinical relevance: bacteremia  —  incidence of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia has increased dramatically over last 15 yr; mortality rate has decreased, but remains high; surgical-site infection  —  compared to infection with methicillin-sensitive S aureus (MSSA), MRSA infection associated with increase in mortality (3-fold), length of stay (by »9 days), and cost (additional $50,000-$60,000); in United States, more peo­ple die of MRSA infections each year than of viral hepatitis, tuberculosis, or AIDS; factors  —  enhanced virulence; vancomycin often inadequate; delay in appropriate antibiotic therapy

History of community-acquired (CA)-MRSA: 1999 report of 4 pediatric deaths from CA-MRSA triggered investi­gation into scope of problem; investigation showed increasing prevalence of MRSA among individuals with no contact with health care settings; in 2006, study showed MRSA responsible for »60% of skin and soft tissue infec­tions seen in urban emergency departments; previously, outbreaks seen among American Indians, urban homeless, and prison populations; more recently, sports participation identified as risk factor; risk factors associated with team sports  —  shared soap or towels; shared whirlpools; abrasions and “turf burns”; cosmetic shaving (eg, among swimmers; causes microabrasions); strains  —  in United States, 8 lineages of MRSA; 2 lineages exclusively found in community samples (ie, did not originate in hospitals)

Characteristics of CA-MRSA: susceptible to most antibiotics (except b-lactams and erythromycin); good colonizer with rapid growth; associated with severe infections (predominantly of skin and soft tissue); patients generally younger and more ethnically diverse (compared to hospital-acquired [HA]-MRSA); virulence factor  —  Panton-Val­entine leukocidin (PVL; potent cytotoxin carried by »5% of S aureus isolates) associated with deceptively deep in­fections (going through multiple planes of tissue); most strains of CA-MRSA PVL-positive, whereas most strains of HA-MRSA PVL-negative

Management of skin and soft tissue infections: incise and drain abscesses; obtain sample for culture; reassess in 48 hr; topical antibiotics  —  mupirocin superior to bacitracin; oral antibiotics  —  trimethoprim-sulfamethoxa­zole (TMP-SMZ) drug of choice for outpatients (in Wisconsin); alternatives include clindamycin (eg, if patient al­lergic to sulfa drugs) and tetracycline; if abscess surrounded by cellulitis, also must cover group A streptococci (add penicillin or use clindamycin, which covers both); for patients with CA-MRSA infections requiring hospital­ization, drug of choice intravenous daptomycin

Transmission: factors  —  direct contact (with infected people or contaminated objects [eg, towels]); compromised skin integrity; crowding; questionable hygiene; carriers  —  >10% of inpatients newly colonized with MRSA de­velop infection during hospital stay; infection risk (and associated mortality) increases with longer-term coloniza­tion (eg, infection occurred in 23% of patients colonized for ³1 yr), but long-term stable colonization poses less risk

Screening: some states drafting legislation requiring screening for all patients admitted to health care facility; study screened all surgical patients; screening identified patients not previously known to be carriers, but did not signifi­cantly affect infection rate

Decolonization: not routinely recommended (recolonization common); beneficial for patients with recurrent (³3 times/yr) skin infections; steps  —  trim fingernails (source of inoculation); apply 0.5 g mupirocin ointment (2%) to anterior nares twice daily for 5 days (approved by Food and Drug Administration); give TMP-SMZ and rifampin (bid) or doxycycline (bid) for 7 days (off-label use); consider washing with chlorhexidine or hexachlorophene body wash (leave on 1 min before rinsing) 1 weekend/mo for 1 yr (may help reduce bacterial count on skin); consider us­ing products with tea tree oil (has activity against staphylococci)

Minimizing risk: prevent colonization with good hand hygiene (in hospital and community) and showering soon af­ter exercising or playing sports; avoid sharing towels and personal items and clean shared equipment; obtain culture samples from abscesses; use antibiotics wisely

Questions and answers: when to use rifampin  —  adding rifampin to TMP-SMZ beneficial for decolonization; less data showing benefit for treatment; problems with drug interactions; rifampin always used as adjunctive agent (monotherapy promotes resistance); decolonizing families  —  if >1 family member has recurrent infections, decolo­nize entire family (using above protocol); education and behavioral interventions (eg, avoiding shared towels and pillowcases) important

Internet Resources

Centers for Disease Control and Prevention: www.cdc.gov/std/ept

California STD/HIV Prevention Training Center: www.stdhivtraining.org

Suggested Reading

Bauer HM et al: California guidelines for expedited partner therapy for Chlamydia trachomatis and Neisseria gonor­rhoeae. Sex Transm Dis 35:314, 2008; Buehlmann M et al: Highly effective regimen for decolonization of methicillin-re­sistant Staphylococcus aureus carriers. Infect Control Hosp Epidemiol 29:510, 2008; Centers for Disease Control and Prevention: Recommendations for partner services programs for HIV infection, syphilis, gonorrhea, and chlamydial infec­tion. MMWR Recomm Rep 57(RR-9):1, 2008; Datta R, Huang SS: Risk of infection and death due to methicillin-resistant Staphylococcus aureus in long-term carriers. Clin Infect Dis 47:176, 2008; Grayson ML: The treatment triangle for staph­ylococcal infections. New Engl J Med 355:724, 2006; Harbarth S et al: Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA 299:1149, 2008; Hum­phreys H et al: Prevention and control of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 15:120, 2009; Kirkland EB, Adams BB: Methicillin-resistant Staphylococcus aureus and athletes. J Am Acad Dermatol 59:494, 2008; Markowitz LE et al: Quadirvalent human papillomavirus vaccine: recommendations of the Advisory Committee on Im­munization Practices. MMWR Recomm Rep 56(RR-2):1; Patel M: Community-associated methicillin-resistant Staphylo­coccus aureus infections: epidemiology, recognition, and management. Drugs 69:693, 2009; Workowski KA, Berman SM: Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis 44(Suppl3):S73, 2007.