ENTERIC INFECTIONS AND HOME IV ANTIMICROBIAL THERAPY
| ENTERIC INFECTIONS, INCLUDING TRAVELER’S DIARRHEA— Herbert L. Dupont, MD, Vice Chairman, Department
of Medicine, Baylor College of Medicine, and Director, Center for Infectious Diseases, University of Texas,
Houston School of Public Health, and Chief of Internal Medicine, St. Luke’s Episcopal Hospital, Houston
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| Diarrheagenic Escherichia coli: enteropathogenic E coli (EPEC)—cause of outbreaks in nurseries; enterotoxigenic E coli
(ETEC)—cause of traveler’s diarrhea and diarrhea in infants and children in developing countries; enteroinvasive E
coli—cause of large foodborne outbreaks; Shiga toxin–producing E coli—O157:H7 strain; enteroaggregative E coli—
produces inflammatory response, but does not invade; cause of traveler’s diarrhea, diarrhea in patients with advanced
AIDS, and persistent diarrhea in children in developing countries
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| Enterotoxigenic E coli: attach to lining of small bowel; release of toxins leads to outpouring of chloride and water; pain
due to serosal stretching of nerve fibers
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| Shiga toxin–producing E coli: ≈70 000 cases per year in United States; found in hamburger meat, wading pools, and produce;
infected child has 10% chance of developing hemolytic uremic syndrome (HUS); some antibiotics (eg, fluoroquinolones,
trimethoprim–sulfamethoxazole) involved in phage induction and stimulate production of Shiga toxin in
greater concentration
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| Enteroaggregative E coli: attaches to epithelial cells; fluoroquinolones and rifaximin effective
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| Shigella: 500,000 cases per year in United States; produces bloody diarrhea and fractional (small-volume) stools; only
hosts are humans and nonhuman primates
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| Nontyphoid Salmonella: 1.4 million cases per year in United States; found in poultry; poultry can become infected
transovarially; poultry infected ≈40% of time in United States; highest incidence of infection in infants <1 yr of age;
due to relative hypochlorhydria, infants predisposed to infection by low doses of Salmonella; bacteremia with Salmonella
infection occurs in patients <3 mo of age or >65 yr of age, patients with AIDS, patients on corticosteroids or hemodialysis,
and patients with inflammatory bowel disease or hemoglobinopathy; treat host carefully
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| Campylobacter: 2.4 million cases per year in United States; 80% of chickens contaminated; 25% to 50% of cases associated
with chicken; risk factors include traveling to high-risk areas; resistance to ciprofloxacin 50% in United States, 90% in Thailand;
leading pathogen-identifiable cause of Guillain-Barré syndrome (associated with 40% of cases; patients with Campylobacter
more sick and develop permanent neurologic sequelae)
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| Clostridium difficile: incidence increasing; 40% occurs in community; risk factors include proton pump inhibitors, antibiotics,
and genetic predisposition; metronidazole failure increasing; nitazoxanide (Alinia) and rifaximin (Xifaxan)
undergoing clinical trials
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| Viral gastroenteritis: rotavirus—principal pathogen in infants <1.5 yr of age; causes vomiting and diarrhea (leads to
rapid dehydration); principal cause of hospitalization of infants in United States; principal cause of death of infants in
developing countries; vaccine licensed in United States; Norwalk virus—outbreak seen in elementary school in Norwalk,
Ohio; principal cause of gastroenteritis worldwide; 23 million cases per year in United States; found on cruise
ships; resistant to Clorox and chlorine; low-dose pathogen; bismuth subsalicylate (BSS; Pepto-Bismol) appears effective
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| Giardia: produces disease at first exposure but not at second exposure; found in daycare centers
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| Entamoeba histolytica: parasite associated with low socioeconomic level; causes abscess in right lobe of liver; more
common in men (11:1 ratio of men to women); women in reproductive years protected from liver abscess; pregnant
women severely affected by disseminated amebiasis; rate of liver abscess in prepubertal and postmenopausal women
same as in men
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| Cryptosporidium and Cyclospora: Cryptosporidium found in tap water; Cyclospora cayetanensis—raspberries imported
from Guatemala caused outbreaks during 1996 to 1997; particularly endemic in Haiti, Peru, and Nepal
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| Traveler’s diarrhea: affects 40% of travelers to developing countries (eg, Mexico); lasts for ≈24 hr; risk factors include
genetic predisposition; follow-up study found 18% of people who developed diarrhea in Mexico still had problems 6
mo later (10% met criteria for irritable bowel syndrome [IBS]); traveling tips—look for heated foods; be careful about
meals served on airplanes; look for steaming hot, dry, or high-sugar (eg, syrups, jellies, honey) foods; do not eat moist
foods at room temperature; rifaximin—study found efficacy in preventing traveler’s diarrhea nearly 80%; decreases
cramps, pain, and gas-related symptoms; 80% of traveler’s diarrhea caused by bacteria; treatment—antibiotics; 200
mg of rifaximin tid for 3 days; levofloxacin; ciprofloxacin; due to increasing incidence of Campylobacter, azithromycin
drug of choice for dysenteric traveler’s diarrhea; give initial dose and, if symptoms persist in morning, give second
dose (third dose can be taken 24 hr later if indicated); ≈70% of patients improve after 1 dose
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| Case presentation: infant 13 mo of age presents with vomiting, low-grade fever, and watery diarrhea leading to dehydration;
infant hospitalized to receive intravenous (IV) fluids; patient has dry mouth and dry eyes; patient somnolent with
10% body weight dehydration (often associated with death); likely causes include rotavirus (more common) or cholera;
treatment of rotavirus—oral rehydration therapy; IV therapy required for patients with 10% body weight dehydration;
enteric vaccine recommended
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| Case presentation: woman 35 yr of age presents with diarrhea and bloody stools; patient has dysentery; likely causes include
Shigella or Campylobacter; treat with azithromycin; diarrhea and bloating persist after 6 mo; woman has postinfectious
IBS
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| Incubation of enteric disease: incubation period 2 hr to 9 days; with lower doses, attack rate lower and incubation period
longer; with higher doses, incubation period shorter; dose does not influence severity of disease
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| Case presentation: 58% of people who attended conference developed symptoms; incubation period 18 hr; 90% developed
vomiting, 60% developed watery diarrhea, and 33% had fever; possible causes include viral gastroenteritis or
preformed toxin (eg, Staphylococcus or Bacillus cereus); viral agent vs preformed toxin—incubation period of viral agent
>14 hr; incubation of preformed toxin 2 to 7 hr; preformed toxins do not cause fever; classic case of Norwalk virus
outbreak
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| Case presentation: woman 80 yr of age develops fever after 4-vessel coronary artery graft; receives antibiotics for 2 wk,
then develops fever, profuse diarrhea, and bloody stool; white blood cell (WBC) count 30,000/µL; woman has C difficile
infection; contracted from spores in hospital; diagnosed by examining stools for toxin; use enzyme-linked immunosorbent
assay (ELISA) or tissue culture testing; latex agglutination testing not accurate; treatment—metronidazole
(Flagyl) recommended but not approved for C difficile; vancomycin licensed and approved for C difficile; relapse rate
30%; rifaximin for 1 mo may prevent second relapse
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| Case presentation: man visited Nepal and developed diarrhea; stool cultures and examinations for parasites negative;
likely causes include C cayetanensis; examinations for parasites look for Giardia, but not Cyclospora (Cyclospora testing
must be requested); trimethoprim–sulfamethoxazole treatment of choice
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| Conclusion: thorough patient history and physical examination important; fluid therapy and symptomatic treatment may
be helpful for patients in United States; empiric therapy indicated for febrile dysentery or traveler’s diarrhea; treat
mild diarrhea symptomatically with Pepto-Bismol; outbreaks of diarrhea require laboratory support
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| HOME IV ANTIMICROBIAL THERAPY— Richard M. Reich, MD, Clinical Associate Professor of Medicine, University
of Wisconsin School of Medicine and Public Health, Madison
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| Introduction: during late 1990s, ≈250 000 courses of outpatient parenteral antimicrobial therapy (OPAT) given per year;
number of courses increasing by ≈20% yearly; OPAT given at home, in infusion centers, physicians’ offices, nursing
homes, hospital-based clinics, emergency department, and dialysis centers
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| Why OPAT growing: safe; potential for cost savings; convenient; new technology (eg, pumps); preferred by patients
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| Parenteral therapy: IV, subcutaneous, and intramuscular therapy; ensures adequate amount of medication delivered
quickly into bloodstream; high concentration of antimicrobials delivered to infected areas; used when oral form of antibiotic
unavailable; ensures patient receives therapy; diagnostic indications expanding (more patients with serious infections
treated once stable); exclusion criteria declining
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| Costs and savings: hospital-based IV therapy $2000/day; high risk for nosocomial infections related to IV therapy (management
of nosocomial infections expensive); patients able to return to work sooner; average savings by delivering antibiotic
therapy at home rather than at hospital ≈$300/day
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| Benefits to patient: patient not separated from family; ≈33% of patients able to work full-time, 33% part-time, and 33%
unable to work; fewer complications related to infection; cheaper; less sleep disruption
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| In-home delivery by nurse: advantages—offers therapy to patients who lack manual dexterity or who are not ambulatory;
offers supervision and assessment of home environment; disadvantages—nurses usually make only 1 visit daily (limits
which antibiotics can be given); higher cost (due to, eg, travel expenses); potential for error because different nurses
may visit home; privacy concerns (patients frequently resent provider’s entrance into home)
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| Home or caregiver administration: advantages—less cost; patient feels more independent; disadvantages—less supervision;
lack of daily care; greater opportunity for noncompliance; less opportunity for ongoing training and patient education
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| Infusion centers: advantages—number of centers increasing; medical resources readily available; medications supervised;
Medicare reimbursement; disadvantages—significant reimbursement penalties against infusion centers (eg,
Medicare does not always reimburse at same rates); patient travel concerns; overhead costs to clinic
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| Nursing home administration: advantages—access to patient by physician; presence of nursing staff; access to medications
and devices; disadvantages—lack of trained personnel; expense of pumps often exceeds cost of nursing home
capitation; difficulty of monitoring
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| Considerations for OPAT: need for parenteral antibiotics vs oral or nasal antibiotics; adequacy of selected site for patient’s
needs (consider patient’s vision and mobility); safety and cleanliness of home; adequacy of communication
among OPAT team; make sure patient and caregiver informed about risks and benefits; follow well-coordinated process
of education for patient
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| Team concept in OPAT: involvement of physician, nurse, pharmacist, patient, and caregiver; case management and administrative
support; involvement of insurance providers
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| Clinical criteria for selection: consider severity of infection (unstable patients not candidates for therapy outside of hospital);
oral therapy not appropriate; consider comorbidities that prevent patients from receiving therapy; patients who need more
intensive nursing may be better candidates for office-based or nursing home–based infusion; patients must be willing and
able to try and comply; drug and alcohol abuse patients often treated in nursing home facilities; consider reimbursement issues
(some insurance companies require 50% deductible)
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| Selecting location and route for OPAT: consider Medicare and other insurance restrictions; Medicare alone does not cover
home IV antibiotic therapy (except in extremely rare cases; consider other sites [eg, office-based or infusion center-
based OPAT]); if patient has insurance coverage, decide whether home delivery appropriate; if regimen complex, programmable
pumps can be used; pumps useful for stable antibiotics that have short half-life (eg, penicillin G); consider
whether patient squeamish about delivering antibiotics, patient’s dexterity, and vision problems; determine whether
nurse-based or caregiver-based administration appropriate
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| Infections treated by OPAT: ≈50% skin, soft tissue, bone, or joint infections; cellulitis treated most commonly; postoperative
wound infections; bacteremia; >50% methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative
staphylococci; Pseudomonas aeruginosa most common gram-negative pathogen; most infections can be treated at home;
OPAT usually delivered for 1 wk; 11-wk course of OPAT reported
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| Considerations for selecting antibiotics: safety; few side effects; well tolerated by patients; for nonhospital administration,
consider stability of antibiotic; cost; avoid using penicillin and gentamicin in patients with nephrotoxicity; ampicillin—
half-life short; must be dosed frequently; unstable at room temperature (cannot be given by infusion pump over 24 hr);
stable at low temperatures; penicillin G—half-life short; stable; well-suited for continuous infusion over 24 hr via programmable
pump; ceftriaxone—used most widely for home IV therapy; half-life long; given once daily for nonmeningitis
indications; stable; 30-min infusion; well tolerated
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| Laboratory monitoring: daptomycin can cause myositis (check creatine phosphokinase [CPK] weekly); check creatinine
periodically; when using penicillins and cephalosporins, monitor complete blood count (CBC) and renal function; semisynthetic
penicillins (eg, nafcillin) nephrotoxic (check creatinine at least twice weekly); aminoglycosides and vancomycin
can cause toxicity or neutropenia (monitor CBC)
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Educational Objectives
| The goal of this program is to educate the listener about diarrheagenic Escherichia coli and home intravenous antibiotic
therapy. After hearing and assimilating this program, the participant will be better able to:
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 | 1. Differentiate strains of E coli based on clinical findings.
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| 2. List risk factors for foodborne infections, such as Salmonella.
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| 3. Treat and counsel patients about preventing traveler’s diarrhea.
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| 4. List advantages and disadvantages of outpatient parenteral antibiotic therapy (OPAT).
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| 5. Determine appropriate OPAT regimens for selected patients.
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Discussed on This Program
Ampicillin [Principen]
Azithromycin [Zithromax, Zmax]
Bismuth subsalicylate (BSS) [Bismatrol, Bismatrol Extra Strength, Pepto-Bismol, Pepto-Bismol Maximum Strength,
Pink Bismuth]
Ceftriaxone sodium [Rocephin]
Ciprofloxacin [Ciloxan, Cipro, Cipro I.V., Cipro XR, Proquin XR]
Gentamicin sulfate (several trade names)
Levofloxacin [Levaquin, Quixin]
Metronidazole (several trade names)
Nafcillin sodium
Nitazoxanide [Alinia]
Penicillin G [Bicillin C-R, Bicillin C-R 900/300, Bicillin L-A, Permapen, Pfizerpen, Wycillin]
Rifaximin [Lumenax, Normix, Xifaxan]
Trimethoprim-sulfamethoxazole (co-trimoxazole; TMP-SMZ) (several trade names)
Vancomycin [Vancocin, Vancoled]
Suggested Reading
Adachi JA et al: Rifaximin: a novel nonabsorbed rifamycin for gastrointestinal disorders. Clin Infect Dis 42:541, 2006;
Connor BA: Sequelae of traveler's diarrhea: focus on postinfectious irritable bowel syndrome. Clin Infect Dis 41 Suppl
8:S577, 2005; Daniels NA: Enterotoxigenic Escherichia coli: Traveler's Diarrhea Comes Home. Clin Infect Dis 42:335,
2006; DuPont HL: What's new in enteric infectious diseases at home and abroad. Curr Opin Infect Dis 18:407, 2005; Esposito
S et al: Outpatient parenteral antibiotic therapy (OPAT) in different countries: a comparison. Int J Antimicrob
Agents 24:473, 2004; Franzolin MR et al: Prevalence of diarrheagenic Escherichia coli in children with diarrhea in Salvador,
Bahia, Brazil. Mem Inst Oswaldo Cruz 100:359, 2005; Goodfellow AF et al: Quality-of-life assessment in an outpatient
parenteral antibiotic program. Ann Pharmacother 36:1851, 2002; Helms M et al: Foodborne bacterial infection and
hospitalization: a registry-based study. Clin Infect Dis 42:498, 2006; Hiramatsu R et al: Ability of Shiga toxin-producing
Escherichia coli and Salmonella spp. to survive in a desiccation model system and in dry foods. Appl Environ Microbiol
71:6657, 2005; Leomil L et al: Characterization of two major groups of diarrheagenic Escherichia coli O26 strains which
are globally spread in human patients and domestic animals of different species. FEMS Microbiol Lett 249:335, 2005;
Sharma R et al: Impact of mandatory inpatient infectious disease consultation on outpatient parenteral antibiotic therapy.
Am J Med Sci 330:60, 2005; Slavik RS et al: Selecting antibacterials for outpatient parenteral antimicrobial therapy: pharmacokinetic-pharmacodynamic
considerations. Clin Pharmacokinet 42:793, 2003; Torres AG et al: Adherence of diarrheagenic
Escherichia coli strains to epithelial cells. Infect Immun 73:18, 2005; Vidal M et al: Single multiplex PCR assay to
identify simultaneously the six categories of diarrheagenic Escherichia coli associated with enteric infections. J Clin Microbiol
43:5362, 2005; Wynn M et al: Evaluation of the efficacy and safety of outpatient parenteral antimicrobial therapy
for infections with methicillin-sensitive Staphylococcus aureus. South Med J 98:590, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has
been disclosed: Dr. Dupont has received research grants and honoraria for speaking from Salix Pharmaceuticals, Inc. Dr.
Reich is on the Speakers’ Bureau for Pfizer US Pharmaceutical Group.
Drs. Dupont and Reich spoke in Madison on December 8, 2005, at the 2005 Update in Infectious Diseases, presented by the
University of Wisconsin School of Medicine and Public Health. Audio-Digest Foundation thanks the speakers and the
University of Wisconsin School of Medicine and Public Health for their cooperation in the production of this program.
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