Infectious Disease Update 2009

From the 16th Annual National Emergency Medicine Conference sponsored by Kaiser Permanente

Gregory J. Moran, MD, Clinical Professor of Medicine, David Geffen School of Medicine at the University of California, Los Angeles

Educational Objectives

The goal of this program is to improve the management of infectious diseases. After hearing and assimilating this program, the clinician will be better able to:

1.   Choose appropriate antibiotics for specific infections, including sepsis, septic shock, bacterial meningitis, and pneumonia.

2.   Recognize when antibiotics are not necessary or when a short course of antibiotics is appropriate.

3.   Discuss the differences between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and hospital-acquired MRSA and the treatment of CA-MRSA infections of differing severity.

4.   Explain the epidemiology of West Nile virus infections and the treatment of Clostridium difficile infections.

5.   Describe the problems expected to be encountered in an influenza epiedemic and the challenges in preparing for one.

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 following has been disclosed: Dr. Moran has received re­search grants from Pfizer, Biosite, Johnson & Johnson, Rib-X Pharmaceuticals, and Agennix, is on the Speakers’ Bureaus of Schering, Pfizer, Cubist, Merck, and Ortho-McNeil, and is a consultant for Cepheid and ProGen Biologics. Dr. Moran also presents information related to off-label or investigational use of a therapy, product, or device. The planning committee re­ported nothing to disclose.

Acknowledgements

Dr. Moran was recorded at the 18th Annual National Emergency Medicine Conference, held March 26-27, 2009, in Ana­heim, CA, and sponsored by Kaiser Permanente. The Audio-Digest Foundation thanks Dr. Moran and Kaiser Permanente for their cooperation in the production of this program.

Antibiotic Update

Community-acquired infections or sepsis: 3 most common organisms Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus; E coli primarily from urinary tract infections (UTIs), S pneumoniae from respiratory infections, and S aureus from different types of infections; methicillin-resistant S aureus (MRSA)  —common cause of severe life-threatening infections from community; treatment regimen should include vancomycin or linezolid

Empirical antimicrobials for community-acquired septic shock: unclear source  —  E coli, S aureus, and S pneu­moniae covered by ceftriaxone with gentamicin or fluoroquinolone (double gram-negative coverage to reduce drug resistance), plus vancomycin (for S aureus and drug-resistant S pneumoniae); hospital or nursing home  —  possible organisms include resistant E coli, Pseudomonas, Enterococcus (universally resistant to cephalosporins), S pneu­moniae, and S aureus; piperacillin with tazobactam (recommended instead of cephalosporin primarily because of Enterococcus) plus aminoglycoside plus vancomycin; drain any fluid collection; debride necrotizing fasciitis; se­vere sepsis from pyelonephritis with obstruction urologic emergency (requires stent)

Bacterial meningitis: for adults and children >2 mo in age  —  causative organisms primarily S pneumoniae and me­ningococcus; ceftriaxone and vancomycin (for drug-resistant S pneumoniae) recommended; unclear whether drug resistance has impact in pneumonia; in meningitis, documented treatment failures with ceftriaxone resistance seen; in elderly or debilitated patients, ampicillin added for Listeria; in newborns  —  concern about group B streptococci (ampicillin and cefotaxime recommended); steroids  —conflicting data; difficult to make evidence-based recom­mendation, as oldest and best studies performed in children with Haemophilus influenzae meningitis (nearly elimi­nated with vaccine); steroids recommended in presence of high clinical suspicion of meningitis, in infants not H influenzae type B (Hib)-vaccinated, positive Gram’s stain, and grossly cloudy cerebrospinal fluid (CSF); speaker often gives first dose of ceftriaxone (2 g) while awaiting results of workup; once meningitis confirmed, add vanco­mycin and steroid; steroid most effective when given at time of first dose or just before first dose; few studies in hu­mans on drug-resistant streptococcal meningitis but rabbit studies show best results with ceftriaxone and vancomycin

Acute otitis media (AOM): push to avoid overuse of antibiotics (leads to drug resistance); >80% resolution rate; ac­ceptable not to treat, especially those with questionable diagnosis; if necessary to treat, amoxicillin drug of choice; poor penetration of fluids in middle ear by cephalosporins; in study of wait-and-see approach for AOM, longer du­ration of earaches and sleepless nights seen; in those given antibiotics, more diarrhea and higher parental satisfac­tion

Acute bronchitis: no benefit seen with antibiotics; studies unable to statistically show faster improvement with anti­biotics; more data to support use of albuterol than antibiotics; acute exacerbation of chronic bronchitis (AECB)  —  better data to support use of antibiotics; study showed reduced duration of symptoms and fewer hospital readmis­sions; organisms usually H influenzae, S pneumoniae, and Moraxella; amoxicillin, macrolides, and doxycycline of­ten used; for subgroup with complicated AECB (frequent exacerbations or poor underlying lung function), appropriate to use second-line agent (eg, amoxicillin-clavulanate [Augmentin], fluoroquinolone)

Pneumonia: S pneumoniae most common causative organism, followed by H influenzae and viruses; most recent In­fectious Diseases Society of America (IDSA) guidelines state that first antibiotic dose should be given while patient still in emergency department (ED; no recommendation for specific hour cutoff, so change likely); increases inap­propriate use of antibiotics; blood and sputum cultures recommended only for severely ill admitted patients; for in­patient community-acquired pneumonia (CAP)  —  3rd-generation cephalosporin and macrolide or fluoroquinolone; for severe pneumonia  —  ceftriaxone or cefotaxime; if risk for Pseudomonas present (eg, hospital, nursing home), give anti-pseudomonal drug, fluoroquinolone (for atypicals, primarily Legionella), and vancomycin; for outpatient CAP  —macrolide or doxycycline; for those with comorbidities or previous use of antibiotics and concerned about resistance, fluoroquinolone; for health care-associated pneumonia  —  those in hospital or nursing home, on dialy­sis, or previously on antibiotics; different bacteriology and higher mortality seen; necessary to cover for MRSA and resistant gram-negative organisms; combination therapy recommended, ie, vancomycin and broad-spectrum antibi­otic for gram-negative organisms

Urinary tract infections (UTIs): uncomplicated cystitis  —studies show short course of treatment acceptable; 3 days more effective than 1 dose; only fluoroquinolones and trimethoprim/sulfamethoxazole (TMP-SMZ; eg, Bactrim) shown effective for short-course treatment; cephalosporins and nitrofurantoin given for ³7 days; acute uncompli­cated pyelonephritis  —  outpatient treatment includes initial dose of ciprofloxacin intravenously (IV; given orally in ED if patient not vomiting significantly) or ceftriaxone IV; fluoroquinolones for 7 days or cephalosporins for ³2 wk used for oral regimens; study showed that ciprofloxacin for 7 days slightly better than TMP-SMZ for 14 days (emergence of sulfonamide resistance)

Sexually transmitted infections (STIs): treatment options for gonorrhea  —  fluoroquinolones no longer recom­mended due to increasing rates of resistance; ceftriaxone or cefixime (now available again); in b-lactam allergy, higher dose of azithromycin used (causes gastrointestinal [GI] upset)

Severe necrotizing infections: clindamycin  —  recommended as part of regimen; observational studies show more fa­vorable results; inhibits protein synthesis (works at ribosome) and some of toxins seen in necrotizing infections; also include broad-spectrum agent (infection often mixed, especially in postoperative diabetic patient); vancomycin included because community-acquired MRSA (CA-MRSA) not universally susceptible to clindamycin; surgical disease; MRSA most common cause of skin infections; for abscesses, speaker uses TMP-SMZ alone; for cellulitis, TMP-SMZ with cephalexin (Keflex) or clindamycin; not clear whether antibiotics necessary after incision and drainage (I and D), even though suspicion for MRSA present; reasonable to use antibiotics (3-5 days) in patients with systemic illnesses, severe cellulitis, diabetes, or failed I and D

Emerging Infections

Emergence of infectious diseases: reasons include global travel, centralized food processing, population move­ments, increased contact with wilderness habitats, human behaviors (eg, sexual, IV drug abuse), and increased use of antimicrobials

Methicillin-resistant S aureus: main complaint often “spider bite”; if giving antibiotic for abscess, ensure that anti­biotic has activity against MRSA; study  —  found MRSA in 59% of skin infections with pus to culture; some re­gional variability; features associated with higher probability of MRSA included abscess, reported spider bite, and previous antibiotic use; no risk factors able to identify patient who requires treatment for MRSA; most pa­tients without MRSA had ³1 risk factors; almost 50% of those with no risk factors had MRSA; CA-MRSA com­pared to hospital-acquired MRSA (HA-MRSA)  —  more susceptible to antibiotics (TMP-SMZ, clindamycin, doxycycline, and rifampin); more aggressive organism; affects young healthy individuals (toxin genes, eg, Pan­ton-Valentine leukocidin [PVL], arginine catabolic mobile element [ACME]); more likely to cause skin infec­tions; causes skin and soft tissue infections, necrotizing pneumonia, endocarditis, septic joint, and invasive bloodstream infections; necrotizing pneumonia  —  case series shows young (average age 21 yr) healthy individu­als affected, with high mortality (>50%); median time from onset of symptoms to death 3.5 days; vancomycin gold standard; clindamycin 85% to 90% susceptibility in CA-MRSA; question of whether inducible resistance clinically significant; some data suggest some advantage over vancomycin with newer drugs (eg, linezolid, dap­tomycin); tigecycline covers gram-negative organisms, and gives broader coverage without use of combination therapy; vancomycin minimum inhibitory concentration (MIC) “creep”  —   even within range of susceptibility, outcomes different; those with higher ranges of MIC obtained better results

Treatment: TMP-SMZ  —  speaker uses alone for patient with MRSA skin abscess with cellulitis or fever; almost no data on treatment of skin infections; cheap and reasonably well tolerated; effective in vitro and in vivo; not effec­tive against Streptococcus (do not use alone for cellulitis without abscess); rifampin  —  rapid resistance when used alone; used for synergy in serious infections, eg, endocarditis; consider for eliminating colonization in pa­tients with recurrent skin infections; satisfactory levels achieved in nose, where carriage of S aureus possible; clindamycin  —anaerobic and streptococcal activity; expensive, with GI side effects; tetracyclines  —  eg, doxycy­cline; reasonably effective; well tolerated and cheap; linezolid  —  highly active; expensive; investigational drugs  —  glycopeptides, eg, dalbavancin, oritavancin, telavancin; all vancomycin-type drugs; ceftobipirole MRSA-active cephalosporin; iclaprim (similar to TMP-SMZ); RX-1741 (similar to linezolid; also covers H in­fluenzae and atypical organisms)

West Nile virus: RNA virus; related to other encephalitis viruses; first seen in United States in 1999; rapid spread through migration of infected birds; significant regional variability in frequency of occurrence (more common in upper Plains); animal reservoirs, but birds main host; spread by mosquitos; human infection incidental; asymptom­atic disease most common manifestation in humans; <1% have severe manifestations of meningoencephalitis (usu­ally in elderly and debilitated patients); common symptoms  —fever, headache, backache, and rash (nonspecific viral symptoms); muscle weakness typical; bird deaths clue; testing  —IgM antibody to virus using serum or CSF; usu­ally performed through state public health laboratories; consider in patients with viral encephalitis, aseptic menin­gitis, and atypical Guillain-Barré syndrome

Clostridium difficile: community strains causing infections in healthy individuals (more toxin production); case defi­nition for community-associated C difficile disease  —  diarrhea, absence of chronic underlying disease, no previous health care facility stay, and laboratory confirmation; treatment  —  metronidazole first choice; for severe cases, con­sider starting with oral vancomycin (concentrates highly in colon); if patient toxic, obtain early surgical consult; avoid antiperistaltic agents; alternative regimens include probiotics, toxin-binding resins, IV immunoglobulin (IVIG), and stool transplantation; changing practice  —  lower threshold for testing for C difficile toxin; consider empiric metronidazole in some cases; nosocomial spread documented; alcohol-based sanitizers ineffective; hand washing important

“Bird flu”: H5N1  —  first known highly pathogenic avian influenza (HPAI) panzootic (pandemic if occurring in hu­mans); peak incidence in 2006; almost all cases resulted from contact with animals; no mutation in virus to allow efficient human-to-human transmission as yet; influenza pandemic certain (although specific virus unknown); hu­man H5N1 concentrated in Southeast Asia presently, but emerging in Middle East and Africa; uncertainties related to pandemic  —  case fatality rate of current virus 20 times that of 1918; unknown whether increased transmissibility associated with less mortality; unknown whether increased transmissibility will be sudden or gradual in occurrence or whether in one or several locations; most influenza transmitted by asymptomatic individuals; problems in event of pandemic  —  vaccine production capacity extremely limited; vaccines tested so far not highly effective; limited supply of antiviral drugs (eg, oseltamivir); potential for resistance to antivirals; imperfect surveillance in animals and humans; Health and Human Services planning assumptions vs total capacity  —  in severe pandemic (like 1918) almost 10 million hospital beds required (actual capacity <1 million beds); almost 1.5 million intensive care unit beds required (actual capacity »87,000 beds); also lack mechanical ventilators, facilities, and staff; key challenges in pandemic influenza preparation  —  demand for care exceeding capacity; preparedness not clearly defined; criti­cal shortage of hospital workers; priorities for planning  —  surge capacity plan; infection control protocols (limit spread of disease in hospital and keep staff healthy); advanced planning protocol (eg, protocols for use of antivirals and ventilators); recommendations  —avoid Asian poultry farms; disaster preparedness; test for influenza, espe­cially if patient traveled to area with bird flu or if severely ill; infection control, eg, respiratory etiquette (encourage patients to wear mask; signs reminding patients to cover mouth when coughing or sneezing); contact local health department if H5N1 suspected

Suggested Reading

Abroug F et al: A cluster study of predictors of severe West Nile virus infection. Mayo Clin Proc. 81(1):12, 2006; Bouza E et al: Antimicrobial therapy of Clostridium difficile-associated diarrhea. Med Clin North Am 90(6):1141, 2006; Confalonieri M et al: Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med. 171(3):242, 2005; Finkelstein JA et al: Watchful waiting for acute otitis media: are parents and physicians ready? Pediatrics. 115(6):1466, 2005; Greenwood BM: Corticosteroids for acute bacterial meningitis. N Engl J Med. 357(24):2507, 2007; Hidayat LK et al: High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med. 166(19):2138, 2006; Katchman EA et al: Three-day vs longer duration of antibiotic treatment for cystitis in women: systematic review and meta-analysis. Am J Med. 118(11):1196, 2005; Lloyd KM et al: Clinical progres­sion of CA-MRSA skin and soft tissue infections: a new look at an increasingly prevalent disease. Arch Dermatol. 144(7):952, 2008; Monto AS et al: Epidemiology of pandemic influenza: use of surveillance and modeling for pandemic preparedness. J Infect Dis. 194 Suppl 2:S92, 2006; Nicoll A: Children, avian influenza H5N1 and preparing for the next pandemic. Arch Dis Child. 93(5):433, 2008; Ong S et al: EMERGEncy ID NET Study Group. Antibiotic use for emergency department patients with upper respiratory infections: prescribing practices, patient expectations, and patient satisfaction. Ann Emerg Med. 50(3):213, 2007; Talmor D et al: Simple triage scoring system predicting death and the need for critical care resources for use during epidemics. Crit Care Med. 35(5):1251, 2007; Wong DM et al: Guidelines for the use of antibiotics in acute upper respi­ratory tract infections. Am Fam Physician. 74(6):956, 2006; Yealy DM et al: Effect of increasing the intensity of implementing pneumonia guidelines: a randomized, controlled trial. Ann Intern Med. 143(12):881, 2005.