Infectious Threats to Women’s Health

Educational Objectives

The goal of this program is to improve management of influenza and methicillin-resistant Staphylococcus aureus (MRSA) infection, with particular attention to the care of pregnant and lactating women. After hearing and assimilat­ing this program, the clinician will be better able to:

1.   Discuss the biology of influenza viruses.

2.   Determine appropriate candidates for influenza vaccination.

3.   Implement antiviral therapy for influenza.

4.   Manage complicated and uncomplicated skin and soft tissue infections in pregnant women.

5.   Prescribe antimicrobial therapy for an MRSA infection during pregnancy.

Acknowledgments

Dr. Winston was recorded at Controversies in Women’s Health, sponsored by the University of California, San Francisco, (UCSF) School of Medicine, and held December 3-4, 2009, in San Francisco, CA. Dr.Liu was recorded at Obstetrics and Gy­necology Update: What Does The Evidence Tell Us?, sponsored by UCSF School of Medicine, and held October 7-9, 2009 in San Francisco. The Audio-Digest Foundation thanks the speakers and the UCSF School of Medicine for their cooperation in the production of this program.

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.

Influenza Update in a Pandemic Year

Lisa Winston, MD, Assistant Professor of Medicine, Division of Infectious Diseases, University of California, San Francisco (UCSF), School of Medicine; Vice-Chief, Inpatient Medical Service and Hospital Epidemiolo­gist, San Francisco General Hospital, San Francisco, CA

Influenza virus biology: single-stranded enveloped RNA virus; mutates rapidly; types A, B, and C; type C does not infect humans; type B infects humans only; one B virus included in seasonal influenza vaccine; not associated with pandemic influenza; type A  —  infects humans, pigs, horses, sea mammals and birds; typed using 2 surface glyco­proteins, hemagglutinin (H) and neuraminidase (N); 9 different N subtypes; H1N1, H1N2, H2N2 and H3N2 known to spread easily in humans; N cleaves sialic acid and releases infectious virus particles (step targeted by neuramini­dase inhibitors); RNA viruses have segmented genome (allows rapid genetic exchange between viruses); antigenic drift  —  constant minor changes due to point mutations (cause of need for annual vaccination); antigenic shift  —  major changes that may be due to reassortment of RNA segments

Morbidity and mortality from seasonal influenza: H1N1 and H3N2 strains responsible in recent years; »200,000 hospitalizations and »36,000 deaths annually in United States; severe disease tends to occur in elderly, very young, and patients with significant comorbidities; ³90% of influenza-associated deaths occur in persons ³65 yr of age (al­most all with comorbid conditions); pandemic influenza  —occurs when population lacks immunity to circulating virus; potentially due to antigenic shift, recirculation of previous virus, or direct transmission from animal to hu­man

Novel H1N1: components of swine, human, and bird types in same virus (triple reassortment virus); “mixing vessel” for 2009 H1N1 presumed to be swine; pigs have receptors for human and avian influenza A viruses; transmitted from humans to pigs, cats, and turkeys; influenza pandemic alert raised from level 5 to 6 in June 2009; among persons ³65 yr of age, hospitalization rates <20% of those expected with seasonal influenza A; about two-thirds to three-quarters of persons hospitalized have known medical risk factor for severe disease (including preg­nancy); hospitalization among pregnant women estimated at »4 times that of general population; risk factors  —  obesity (especially body mass index [BMI] >35) and pregnancy; H1N1 influenza in Australia and New Zealand (2009)  —  highest rate of intensive care unit (ICU) admissions among persons <1 yr of age; »9% pregnant women; 28.6% had BMI >35; »30% had no known predisposing risk factor; mortality »17%; »5% of ICU bed days over 3-mo period accounted for by patients with influenza (peak of 19% in some regions); pregnancy indi­cation for vaccination for and treatment of infection with both novel H1N1 and seasonal influenza; treatment of­ten based on symptoms, without confirming test

Virulence: animal models show transmissibility similar to that of seasonal influenza virus (bronchopneumonia more severe than seasonal influenza in mice, ferrets, and primates); bacterial coinfection  —  postmortem study showed evidence of concurrent bacterial infection in »30% of patients (Streptococcus pneumoniae most common organism); methicillin-resistant Staphylococcus aureus (MRSA) significant pathogen in postinfluenza pneumo­nia; severe illness indication for treatment for bacterial pneumonia

Indications for vaccination: initial target groups for novel H1N1 vaccine  —  pregnant women; persons residing with or providing care to infants <6 mo of age; health care and emergency services personnel; persons 6 mo to 24 yr of age (because of high morbidity in younger age groups); persons 24 to 65 yr of age with medical risk factors; »159 million persons in United States in initial target groups; indications for seasonal vaccine  —  adults >50 yr of age; all children; persons >6 mo of age with chronic medical condition; residents of long-term care facilities; pregnancy; health care workers; healthy persons with high-risk contacts; »83% of United States population

Novel H1N1 monovalent vaccine: contains A virus strain; same manufacturing processes as for seasonal vaccines; none contains adjuvants; propagated in eggs; indications  —  children 6 mo to 9 yr of age, 2 doses; persons ³10 yr of age 1 dose (provides good immunity); complication rate lower than expected

Influenza vaccines: trivalent inactivated vaccine (TIV)   —  2 A virus strains and 1 B virus strain; approved for per­sons ³6 mo; severe egg allergy only contraindication; sore arm most common side effect; live attenuated intranasal vaccine (LAIV [eg, FluMist])  —  H1N1 version more widely available than injectable; same viral strains as inacti­vated vaccine; attenuated, heat-sensitive, and cold-adapted; replicates in nose, but not in lower respiratory tract; ap­proved for healthy persons 2 to 49 yr of age; runny or stuffy nose most common side effect; who should not receive LAIV  —  persons aged <2 yr or >49 yr; persons with chronic medical conditions; pregnant women; persons with his­tory of Guillain-Barré syndrome; persons allergic to eggs; persons coming in contact with highly immunosup­pressed patients (eg, HIV or bone marrow transplant patients); breastfeeding not contraindication; studies show LAIV more efficacious than TIV in children than adults

Prevention: vaccination of health care personnel  —  many elderly and debilitated persons do not have robust immune response to vaccine; health care personnel transmit and acquire influenza; influenza virus shed before symptoms develop, and some infections asymptomatic; data show vaccination can decrease some manifestations of influenza infection and absenteeism in working adults; vaccination associated with decreased patient mortality in long-term care facilities (dependent on efficacy of current vaccine); California requires that health care personnel working in acute facilities receive vaccination or sign declination; use of masks  —conflicting evidence regarding efficacy; Cen­ters for Disease Control and Prevention and Institute of Medicine recommend fit-tested N95 respirator mask for health care personnel; data on efficacy of N95 respirator vs surgical mask conflict (speaker advises using either)

Antiviral agents: adamantanes  —  not active against influenza B; N inhibitors  —  zanamivir (inhaled) and oseltamivir (Tamiflu; oral); clinical illness reduced by »1 day when given to patient with regular seasonal influenza within 48 hr of onset of symptoms; observational data show oseltamivir decreased lower respiratory tract complications, overall antibiotic use, and hospitalization rates; treatment of hospitalized adults with oseltamivir associated with decreased mortality; some reports suggest benefit of early administration in patients with H1N1; resistance  —  most seasonal influenza A viruses (H1N1 strains not currently in circulation) resistant to oseltamivir, and many resistant to adamantanes (amantadine and rimantadine); novel influenza A (H1N1) viruses resistant to adamantanes; occa­sional isolates resistant to oseltamivir, but susceptible to zanamivir; priority for treatment  —  more severe illness, especially hospitalized patients; children <2 yr of age; adults ³65 yr of age; pregnant women; significant comorbid­ities predisposing to severe influenza; children receiving long-term aspirin therapy

Diagnosis: signs and symptoms nonspecific; rapid influenza tests lack sensitivity; influenza-like symptoms in high-risk group may be indication for treatment without testing; polymerase chain reaction (PCR) or viral culture used in hospitalized patients

Comparative severity: avian influenza (H5N1)  —  sporadic human cases continue in several countries; 60% case fa­tality rate; inefficient person-to-person transmission; 1918-19 pandemic  —  mortality <2% in most populations; novel H1N1  —  <0.1% mortality rate; as of November 2009, »22 million infected, with »4000 deaths

Methicillin-resistant Staphylococcus aureus (MRSA) in Obstetrics and Gynecology

Catherine Liu, MD, Assistant Clinical Professor, Department of Medicine, Division of Infectious Diseases, UCSF, School of Medicine

MRSA active surveillance cultures (ASC): required in California within 24 hr of admission for patients scheduled for inpatient surgery, discharged from acute care hospital during past 30 days, admitted to ICU, receiving inpatient dialysis, or transferred from skilled nursing facility; rationale for ASC  —  prevents patient-to-patient transmission (by using contact precautions, isolation, and/or decolonization); prevents subsequent infection of previously colo­nized patients; enables appropriate modification of perioperative prophylaxis; conflicting data supporting ASC led professional societies to conclude evidence insufficient to warrant routine or mandated use of ASC for detection of MRSA

Contact isolation: supporting data inconclusive; potential adverse events associated with contact precautions (pa­tients likely examined less frequently and for shorter periods, compared to nonisolated patients); patients more likely to experience preventable adverse events (eg, pressure ulcers, falls, electrolyte imbalances); increased rates of depression and anxiety; trial currently ongoing to address question of whether intensive infection control strate­gies reduce transmission of pathogens

Origin of community-acquired MRSA (CA-MRSA): 4 deaths due to MRSA reported in previously healthy chil­dren in 1999; outbreaks of CA-MRSA then reported in multiple diverse populations; 2006 paper cited CA-MRSA as predominant cause of skin and soft tissue infection among patients presenting to 11 emergency departments; likely arose de novo from acquisition of resistance by methicillin-susceptible strain; CA-MRSA genetically distinct from hospital-acquired MRSA (HA-MRSA); has novel staphylococcal chromosomal cassette element; lacks multi­ple antibiotic resistance genes; contains other genetic elements that may contribute to virulence

Spectrum of disease: skin and soft tissue infections most common, followed by wound infections, urinary tract in­fections, and bacteremia; CA-MRSA more susceptible to non–b-lactam antibiotics (compared to HA-MRSA); Co­chrane Database of Systematic Reviews (2008)  — reported reduction of nosocomial S aureus infections in surgical and dialysis patients; however, most patients had methicillin-sensitive S aureus (MSSA), and those with MRSA had HA strain; studies of nonsurgical patients and MRSA carriers showed no benefit; 2003 review  —  topical mupirocin and systemic antimicrobial therapy not effective in eradicating nasal or extranasal MRSA; adverse events and de­velopment of resistance observed with oral systemic decolonization

MRSA carriage in pregnancy: approximately one-third of women carriers (1% colonized with MRSA; both rates consistent with general population); 5% of infants carriers (<1% MRSA); no evidence of maternal-infant transmis­sion; vaginal-rectal colonization  —  prevalence 0.4% to 3.5%; conflicting data on association with Group B strepto­coccus carriage; data looking at colonization and risk for vertical transmission showed no cases of early-onset invasive neonatal MRSA infections; no evidence of substantial cost benefit with MRSA screening and decoloniza­tion, regardless of success of treatment; perioperative prophylaxis  —  meta-analysis of cardiac surgery patients treated with vancomycin or b-lactam showed no increased benefit from use of either drug; vancomycin did appear to reduce rate of surgical site infection in subgroup of patients with MRSA; threshold prevalence of MRSA infec­tions for changing prophylaxis regimens not yet defined; protocol at UCSF  —  perform ASC on selected patient group; focus on education of patient and health care personnel to reinforce standard precautions and hand hygiene

MRSA in pregnancy: clinical presentation  —  data show majority of infected patients multiparous; clinical infection mostly during second trimester; mastitis and surgical site infection most common postpartum infections; skin and soft tissue infections predominant clinical presentation; data show no significant difference in obstetric outcomes between women with CA-MRSA and those without CA-MRSA; postpartum mastitis  —  data show no difference in age, pregnancy history, clinical presentation, or prenatal or intrapartum risk factors; patients more likely multipa­rous (may reflect increased prevalence of MRSA among children); no significant differences in clinical outcomes with antibiotic use; MSSA predominant organism in women without abscess; MRSA dominant organism in women with abscess; MRSA and MSSA significant pathogens in nonpuerperal mastitis; management of uncomplicated skin and soft tissue infections  —  incision and drainage (I and D) primary treatment; benefit of antibiotic beyond that of I and D unknown; consider empiric treatment with systemic symptoms, severe local symptoms, or immunosup­pression; antibiotics may have more important role in patients treated with minimally invasive drainage techniques; empiric therapy  —  if abscess present and antibiotic therapy indicated, consider coverage for CA-MRSA (pending culture); for mastitis without abscess, consider coverage for CA-MRSA based on local epidemiology or failure to respond to b-lactam therapy

Antimicrobial therapy: co-trimoxazole (TMP/SMX)  —  low rate of resistance; covers MRSA and MSSA; unreliable for group A streptococcal infection; pregnancy category C or D in third trimester; clindamycin  —  covers MRSA, MSSA, and group A streptococci; excellent tissue and abscess penetration; potential for resistance; risk for Clos­tridium difficile; pregnancy category B; doxycycline  —  low resistance; covers MRSA and MSSA, but unreliable for group A streptococci; pregnancy category D; linezolid  —  indicated for complicated skin and soft tissue infections; adverse events associated with long-term use (eg, potential bone marrow suppression, neurotoxicity); pregnancy category C; inducible clindamycin resistance  —  not detected by standard broth microdilution testing; consider with erythromycin-resistant but clindamycin-susceptible isolate; if disk diffusion-test positive but patient improving, continue clindamycin; change therapy with failure or moderately severe infection; management of complicated skin or soft tissue infections  —  empiric therapy for MRSA recommended (vancomycin first-line drug); daptomycin (pregnancy category B) and tigecycline (pregnancy category D) approved; no significant difference in primary out­come of clinical cure among these 4 drugs

MRSA and breastfeeding: one case report of transmission of MRSA via breast milk (mother asymptomatic); no clear data on whether woman with postpartum mastitis should continue breastfeeding; breast emptying mainstay of therapy; some experts recommend continuing breastfeeding if mother on antibiotics, unless draining wound or cel­lulitis in area; another recommends breastfeeding on contralateral side and expressing on infected side

Vulvar abscesses: data show MRSA dominant pathogen in 64% of women treated for vulvar abscess; no distinguish­ing clinical signs or symptoms; no difference in clinical outcomes; perform I and D; treat with TMP/SMX (covers MRSA and majority of other pathogens)

Suggested Reading

Andrews JI et al: Screening for staphylococcus aureus carriage in pregnancy: usefulness of novel sampling and culture strategies. Am J Obstet Gynecol 201:396, 2009; Webb SA et al: Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 361:1925, 2009; Beigi RH et al: Epidemiologic and economic effect of methicillin-resistant Staphylococcus aureus in obstetrics. Obstet Gynecol 113:983, 2009; Chen KT et al: Prevalence of methicillin-sensitive and methicillin-resistant Staphylococ­cus aureus in pregnant women. Obstet Gynecol 108:482, 2006; Kolef MH: New antimicrobial agents for methicillin-resistant Staph­ylococcus aureus. Crit Care Resusc 11:282, 2009; Laibl VR et al: Clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus in pregnancy. Obstet Gynecol 106:461, 2005; Milstone AM et al: Fact, fiction, or no data: what does surveil­lance for methicillin-resistant Staphylococcus aureus prevent in the intensive care unit? Clin Infect Dis 46:1726, 2008; National center for Immunization and Respiratory Diseases, CDC; Centers for Disease Control and Prevention (CDC); MMWR Recomm Rep 58:1, 2009; Stafford L et al: Community-acquired methicillin-resistant Staphylococcus aureus among patients with puerperal mastitis re­quiring hospitalization. Obstet Gynecol 112:533, 2008; Thurman AR et al: Methicillin-resistant Staphylococcus aureus as a com­mon cause of vulvar abscesses. Obstet Gynecol 11:538, 2008; Trifonov V et al: Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. N Engl J Med 36:115, 2009.