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Gastrointestinal infectionsJoanne Engel, M.D., Ph.D.

ProfessorDepts of Medicine and

Microbiology/ImmunologyUCSF

Thanks to Drs. Sarah Doernberg, Bryn Boslett for sharing some slides

Disclosures

None

Updates on:• Food-borne GI illnesses with a focus on

infectious diarrhea– IDSA 2017 Diarrhea guidelines– Traveler’s diarrhea, C. diff covered elsewhere

• Abdominal infections– IDSA 2011 guidelines/surgical infection society

2016– Diverticulitis– Appendicitis

Diarrhea: a global cause of disease

• 2nd leading cause of morbidity/mortality worldwide

• In the US– 200-375 million episodes/year– 180 million outpatient visits– 500,000 hospitalizations– > 5000 deaths– Each person has 1-2 diarrheal illnesses/yr

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Case 132 yo female calls your office c/o diarrhea x 2 days. She notes 8 loose stools in the past 24 hrs. She has a low grade temp, mild nausea, and has vomited x 2. She denies bloody stools, recent travel, ingestion of unsual foods. No sick contacts.

Diarrhea“Passage of 3 or more loose or liquid stools

per 24 hours, or more frequently than is

normal for an individual”

- WHO

Definitions

AcuteLasts <7 days

Acute vomiting +/- diarrhea = gastroenteritis

ProlongedLasts 7-13 days

PersistentLasts 14-29 days

ChronicLasts 30 days or longer

Differential Dx• Infectious• Ischemic• IBD• Iatrogenic/Osmotic• Malabsorption

The players aka �The dirty laundry list�Viral Bacterial ProtozoalCalicivirus (Norwalk,

Norovirus, Sapovirus)Salmonella 16.4* Giardia

Rotavirus Campylobacter 14.3* E. Histolytica

Adenovirus Shigella 2.3* Cryptosporidium 1.4*CMV Yersinia 0.3* Microsporidium

Astrovirus E. coli (shiga toxin) 1.1* Cyclospora

Small round virus C. difficileCorona virus C. perfringens

HSV S. aureusBacillus

Vibrio 0.4Listeria

Chlamydia, GC *cases per 100,000 in US

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Some enteric pathogens are very infectious

Organism InoculumShigella 10-100Giardia 30-100Cryptosporidium parvum 30-100Shigatoxin-producing E. coli 10-100Norovirus 10-100Salmonella 103-105

Campylobacter 103-106

Cholera 106

ETEC 108

A little goes a long way…

Symptoms: not really specific• Bloody diarrhea

– In USA: Shigella, Campy, Salmonella, Shigatoxin-producing E. coli– Consider also: Amoebiasis, Vibrio, Aeromonas, Yersinia, Plesiomonas

• Watery diarrhea– ETEC, enteric viruses, Cryptosporidium parvum, Cyclospora cayetanensis,Vibrio

• Fever: Implies inflammation, consider:– Invasive bacteria (Salmonella, Shigella, Campy)– C. diff– Noro/rotavirus

• Vomiting– Viral gastroenteritis– Preformed toxin (incubation 2-7 hours): B. cereus, Staph aureus– Anisakiasis

• Non-GI syndromes– Fish and mushroom toxins, botulism, Listeria, Typhoid, HAV, Toxoplasma,

Brucella Talan D et al., Clin Infect Dis. 2001 Feb 15;32(4):573-80

Back to the patient: Take a good history

• When & how illness began• Stool characteristics• Frequency & quantity• Presence of dysenteric symptoms• Symptoms of volume depletion• Associated symptoms• Epidemiologic clues

Be a Sherlock Holmes• Travel to developing area• Food-handler or caregiver• LTCF or Day-care center attendance or employment– “a veneer of feces”

• Recreational water venues• Consumption of raw meats, eggs, unpasteurized

milk/cheese, swimming in or drinking from untreated fresh water

• Farm or zoo animals, reptiles• Exposure to other ill persons• Medications, esp antibiotics• Underlying medical conditions, HIV, IC• Receptive anal intercourse or oral/anal contact

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Etiology of severe acute gastroenteritis in adults in ER

• Prospective multicenter ER-based study• Pathogens found in ~50%• Norovirus comprises 50% of identified

pathogens; 25% of all cases

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Bresee et al, JID, 2012

When should you do a work-up?

• Duration >3-7 days – viral diarrhea usually resolves within 3 d

• > 24 hours if associated with blood; “mod-severe disease”– Fever, bloody or mucoid stools, severe abd cramping or

tenderness, signs of sepsis (2017 IDSA guidelines)• Hospital admission• Immunocompromised patients• Outbreak settings

– Even if not useful for rx, can have public health benefit• Risky patients: HCW, food handlers, daycare, LTCF• Persistent diarrhea

Guerrant RL et al. Clinical Infectious Diseases ; 2001 ; 32 : 331 -35Riddle et al, AJG, 2016

Infectious causes of persistent diarrhea• Definition

– Persistent diarrhea > 14 days– Chronic diarrhea > 4-6 weeks, not usually infectious in etiology

• 3% of returning travelers• Enteric parasites

– Giardia: Freshwater, daycare centers– E. histolytica– Cryptosporidium: Human and animal reservoir, drinking water, low inoculum– Cyclospora: Nepal, Haiti, Peru, Guatemalan rasperries, seasonal– Isospora– In HIV, consider Microsporidia, MAC

• Bacteria: Shigella, enteroaggregative E. coli• Post-infectious IBS

– ~10-15% vs. 2% in the general population• Brainerd diarrhea

– Acute watery diarrhea > 4 wks no identified cause– Can occur as outbreaks– Resolves w/o treatment Dupont, HL. JAMA. 2016

What’s the work-up• Stool cx (or multiplex PCR) for Salmonella, Shigella, Campy,

STEC,– O157 is sorbitol-; Non-0157:H7 STEC are sorbitol +, need to also order

Shiga-toxin by EIA or NAAT

– Shellfish-assoc or cholera suspectedàsalt-containing media – Yersinia if Europe, appendicitis-like sx, exposure to undercooked pork

– Rectal swab if no stool sample (but less sensitive)

• Blood cultures if septic, suspicion for S. typhi, IC• C. diff toxin/PCR

• Rotavirus Ag (esp in kids)

• Parasites (if persistent or host factors):– Stool O+P– Giardia Ag

– Coccidia exam (Cyclospora, Isospora, Cryptosporidium)– Modified trichrome stainàMicrosporidia

• STI risks: RPR; GC and Chlamydia (incl LGV work-up if positive)

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Bloody stool w/u

EIA for toxin NAAT for Stx genesEHEC

sorbitol negativeSTEC

FDA approved Multiplex PCR

Riddle et al, AJG, 2016

• Very sensitive and rapid• Does not distinguish between active vs recent past

infection• Culture still needed for cases reported to public health

(allows for epidemiology, abx resistance testing )

What’s the work-upEmpiric Abx Rx

• Bloody diarrhea: challenge is to distinguish Shigellafrom STEC before test results avail.– Freq scant bloody stools, fever, cramps, tenesmus– STEC: “all blood, no stool”; 90% bloody at some point,

fever rare (non-invasive bacteria)

• Travel to developing nations T>38.5 and/or signs sepsis (concern for bacterial diarrhea)

• Cipro or azithromycin if STEC not suspected• IC pts with severe illness and bloody diarrhea

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Ancillary management

• Anti-motility agents: Avoid in C. diff, Shigella• Anti-emetics if vomiting• Probiotics– No harm– Variability in preps– Data variable

Probiotics• Mixed messages in guidelines from US and European

associations

• Cochrane meta-analysis (2010) concluded that there were only 10 trials that could provide useful info

• 2017 IDSA recs: “most trials report decrease diarrhea duration and stool frequency w/sustained benefit across all outcomes”

• 2 recent studies (NEJM Nov 2018) examined children age 3-48 mos who presented to ER with <72 hrs of mod-severe gastroenteritis

– Randomized to receive 5 days probiotics (Lactobacillus rhamnosis) or placebo 2X/day

– Composite endpoints

– Both trials failed to show efficacyFreedman et al,; Schnadower, D. et al; see also editorial by LaMont et al

Back to the case32 yo female calls your office c/o diarrhea x 2 days. She notes 8 loose stools in the past 24 hrs. She has a low grade temp, mild nausea, and has vomited x 2. She denies bloody stools, recent travel, ingestion of unusual foods. No sick contacts.– No unusual exposures– Only sick for 2 days– No blood or sx of dysentery– Not severe– Probably viral– Supportive home therapy

Case 2• 25 attendees of the ID holiday party become ill, and

you are suspicious for a foodborne disease• Median incubation period = 28 hours• 90% with vomiting • 50% with diarrhea• 30% with fever• Recovery occurred in 12-60 hours

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What is the etiology?A. NorovirusB. Shigella sonneiC. Staphylococcus aureus enterotoxinD. C. perfringensE. B. cereus

Foodborne disease by incubation period

• < 2 hours: Chemical agent – scrombroid, ciguatera, mushroom toxins, etc

• 2-7 hours: Preformed toxin (except C. perfringens)– Staph aureus, B. cereus

• 8-14 hours: C. perfringens– Not necessarily more severe

• > 14 hours: Most viruses and bacteria

What is the etiology?A. NorovirusB. Shigella sonnei– Diarrhea predominates

C. Staphylococcus aureusenterotoxin– Too long an incubation– No fever

D. C. perfringens– Too long incubation– Vomiting is unusual

E. B. cereus– Too long incubation

• Used to determine if outbreak likely 2/2 Norovirus

• 99% sp, 68% sn if all criteria met

1. Mean/median illness duration of 12-60 hrs

2. Mean/median incubation period of 24-48 hrs

3. > 50% of people with vomiting

4. No bacterial agent found

• Single (+) stranded, noneveloped RNA virus

• Caliciviridae family• Genogroups->genotypes->strains– GII.4 associated with more severe

outcome (JID 2018)• Replicates only in GI tract• Persists in environment• Humans are the only reservoir

Glass et al, NEJM, 2009

Norovirus

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Sx

• Inc 12-48 hrs (mean 33 hrs)• Sudden onset diarrhea, vomiting, abd pain,

malaise, low grade fever– Profuse and projectile

• Usually self-limited, resolves ≤ 3 d– Prolonged and severe sx in elderly, very young, IC pts– Prolonged asymptomatic shedding

• Up to 8 wks in healthy pts• Up to 1 yr in severely IC pts

Larry the vomiting robot

Dx

• Not culturable

• Gold standard: RT-PCR (since early 1990’s)

– 68% sensitive

– 99% specific

– Available at public health depts, state & national

labs, sendouts, or your lab (syndromic RT-PCR

panel)

Evolving epidemiology• Most common cause of gastroenteritis• Leading cause of diarrhea• Leading cause of foodborne-associated illnesses• Responsible for 50% of gastroenteritis

outbreaks worldwide• Greatly under-reported– Only 1/1562 cases identified– ~21 million cases/yr US– ~2.1 million ambulatory visits/yr– ~71,000 norovirus-associated hospitalizations

costing $493 million/yr (CID 2011: 52, 466)– ~800 deaths/yr US– 200,000 deaths annually children <5 developing nations CDC

Gastanaduy et al, JID, 2013

Norovirus is a moving target• Antigenic shift and drift (like

influenza)– Change in viral capsid affects binding to

GI tract oligosaccharides– New variant->new epidemic wave– New pandemic strain every 2-4 yrs

• GI, GII, GIV genotypes cause most human infxns– GII.4 strains predominant since 1990’s– GII.4 Sydney strain, GII.p17, GII.17– Continue to evolve q 2-3 yrs

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Why is norovirus so difficult to contain?• Highly transmissable: a little goes a long

way…– ID50: 10-100 virions– Facile 2˚ spread• Viral shedding precedes clinical illness in >30% of pts • Prolonged shedding

– Up to 8 wks in healthy hosts– Up to 1 yr in IC hosts

• Asymptomatic shedders– Withstands wide range of temps and persists in

environment– Immunity is short-lived and not cross-protective

against antigenic variants

Why is norovirus so difficult to contain?

• Multiple modes of transmission– Food (30%)

• Globalization of food distribution• Increased # of people who handle the food we eat• Increased consumption of food at risk of contamination

(fresh vegetables and fruit)– Water– Airborne via vomitus

• Susceptibility correlates w/distance from vomiting event– Contact w/contaminated surfaces– Fomites– Person-person contact– Resistant to many disinfectants

Interrupting transmission• Disinfection– Wipe surface w/detergent to remove particle

debris followed by hypochlorite bleach (5000 ppm) as disinfectant

– Other disinfectants less efficient: (quanternary ammonium compounds, alcohols)

– Alcohol-based disinfectants are insufficient• Wash hands for 1 min w/soap & water,

rinse for 20 sec, dry w/disposable towels

Interrupting transmission• Institutional settings– Cohort pts and staff– Minimize transport, visitors– Isolation, contact precautions for sick pts (48 hrs after sx

resolve)– Sick staff stay home until 48 hrs after sx resolve– Alcohol in, soap& water out

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Norovirus: The perfect pathogen?• Highly contagious• Rapidly & prolifically shed• Constantly evolving• Evokes limited immunity• Only moderately virulent—doesn’t kill host

Planning your next cruise….Cdc vessel sanitation site

CID 2010; 50:133-164

See also:

IDSA guidelines 2010 A few definitions

• Complicated intra-abdominal infection: �extends beyond hollow viscous of origin into peritoneal space and is associated w/abscess formation or peritonitis�

• And 111 guidelines…

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More definitions

• Mild-moderate severity community acquired (CA)

infection

• Severe CA infection:

– age >70

– medical comorbidities

– poor nutritional status

– major peritoneal soilage or multiple abscesses

– patient hemodynamically unstable

– source control delayed or not feasible

• HA associated

– invasive device

– h/o MRSA infxn or colonization

– h/o surgery, hospitalization, dialysis, or LTHCF in previous 12 mos

Case 3

• 44F with no prior medical history presents to ED with several hrs of diffuse abdominal pain and chills.

• Tc 37.8C, HR 85, BP 140/80, SaO2 100% RA. • WBC 16K, other labs normal. UA and pregnancy

test negative.

• Empiric Abx?• If so, which ones

Source control• Diffuse peritonitis due to perforated viscous is a

surgical urgency

• If possible, percutaneous drainage of abscesses is preferred– But not if there is a perforated viscous

• Not enough data to support specific approaches– E.g. extent of resection/debridement, anastamosis vs.

ostomy, what tissue is debrided, wound management technique

• Highly selected patients who are clinically stable with a well-circumscribed focus of infection may be treated with antibiotics alone, provided that very close follow-up is possible Solomkin JS et al., Clin Infect Dis ; 2010 ; 501 : 133 -164

Does she need antibiotics now?

• Cholangitis – decreased rates of complication• Cholecystitis – lack of data, but usually done• Diverticulitis – no longer routinely recommended in

mild uncomplicated disease (but lowest level of evidence)

• Appendicitis – generally yes.– Select cases: abx preferred over surgery, but this approach

still not widely recommended

IDSA guidelines: Antibiotics indicated as soon as Dx of hollow viscous infection/rupture is made or suspected – within 1 hr for septic patients, within 8 hrs for hemodynamically stable pts

Gastroenterology 2015;149:1944 – 1949.

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Case continued…

• CT scan -> cholecystitis • Surgery planned for tomorrow • NKDA

• Which antibiotics?

Abx selection• Empiric rx according to predicted flora and

likelihood of abx resistance– Narrower spectrum for mild-mod CA infxns– Broader coverage (MDR GNR, enterococcus, yeast) for

severe HCA infxns

Oral flora

Miami beach for bacteria

Microbiology

• Organisms identified in 3 randomized prospective studies (N=1237)

• Bacteremia is uncommon– 0-5%, more

likely in critical illness

Solomkin JS et al., Clin Infect Dis ; 2010 ; 501 : 133 -164

Organism % of ptsEscherichia coli 71

Klebsiella species 14

Pseudomonas aeruginosa 14Proteus mirabilis 5

Enterobacter species 5

Bacteroides fragilis 35

Other Bacteroides species 71Clostridium species 29

Prevotella species 12

Peptostreptococcus species 17

Fusobacterium species 9

Eubacterium species 17

Streptococcus species 38

Enterococcus species 23

Staphylococcus aureus 4

Empiric therapy for mild to mod CA infections

at UCSF

Severity Drug(s) of First Choice Severe PCN allergy

Mild-ModerateCA

Ertapenem 1g IV dailyOR

Piperacillin/tazobactam 3.375 g IV - 4.5g IV q6h

ORCeftriaxone 1 g IV daily

PLUSMetronidazole 500 mg IV

q8h

VancomycinPLUS

Aztreonam 2 g IV q8hPLUS

Metronidazole 500 mg IV q8h

Do not need to cover Pseudomonas, Enterococcus, yeastDo cover for enteric gram-negative aerobic and facultative anaerobic bacilli and enteric gram-positive streptococci

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Case continued…• Ertapenam started• Successful cholecystectomy• Doing well POD2, ready for d/c

• How long to continue abx?

Duration of therapy

• If no perforation or evidence of abscess, d/c abx24 hrs after surgery –

• No evidence to use abx prophylaxis for the drain!

Case continued…• Pt dc’d home • Next day, surgeon calls. Intraoperative tissues sent

for culture growing Enterococcus species (among other things)

• Pt is clinically stable

• Were cultures appropriate?• Do you need to restart abx?• Does enterococcus need to be covered?

Role of intra-operative cultures

• Cultures optional in low risk CA infection, but “may be of value in detecting epidemiological changes in resistance patterns”

• Anaerobic cultures not necessary if abx regimen covers anaerobes

• Gram stain generally NOT useful in CA infections, but may be useful in HCA infections if yeast is shown

• For low risk CA infections, uncovered organisms do not need to be covered unless pt fails to improve

• For severe or HCA infections, consider on case-by-case basis

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How should microbiology data guide treatment?

• If good response to source control and initial abx, no need to change even if untreated organisms are found

• Use microbiology to guide therapy if not responding well to empirical abx

• For severe or HCA infections, pathogenic potential and density of organisms should be considered

Solomkin JS et al., Clin Infect Dis ; 2010 ; 501 : 133 -164

Role of Enterococcus

• Unclear role as pathogen, no good studies• Found in 20% of intra-abdominal infections• Regimens that don’t cover enterococcus work for

community acquired infections

Case 4• 68M h/o BPH and recent hospital admission two

months ago for UTI / pyelonephritis treated with ceftriaxone

• Presents w/ T 38.5C, RUQ abdominal pain, WBC 16K, elevated Tbili

• CT scan: acute cholangitis.• What organisms to cover for empiric Rx?– Pseudomonas?– Enterococcus?– Yeast?

Micro of CA vs. HA infectionsMicroorganism CA HA P value

Escherichia coli 159 (72%) 65 (52%) <0.001

Klebsiella spp. 15 (7%) 13 (10%) NSEnterobacter spp. 28 (13%) 23 (19%) NSProteus mirabilis 9 (4%) 7 (6%) NSPseudomonas aeruginosa 11 (5%) 16 (13%) <0.01Enterococcus faecalis 28 (19%) 31 (33%) <0.05Enterococcus faecium 16 (11%) 8 (8%) NSEnterococcus (other) 13 (9%) 13 (14%) NSStreptococcus spp. 74 (50%) 29 (31%) <0.01Staphylococcus aureus 11 (7%) 6 (6%) NSBacteroides spp. 74 (56%) 30 (53%) NSClostridium spp. 19 (14%) 10 (18%) NSFungi 19 (3%) 13 (4%) NS

Montravers P et al., J Antimicrob Chemother2009;63:785-94

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Empirical coverage severe CA or HA associated infections

Severity Drug(s) of First Choice Severe PCN allergy

Severe

VancomycinPLUS

Piperacillin/tazobactam4.5 g IV q6h

(For hemodynamically unstable health-care associated infection,

consider meropenem)OR

Ertapenem 1g IV dailyOR

Piperacillin/tazobactam 3.375 g IV - 4.5g IV q6h

VancomycinPLUS

Aztreonam 2 g IV q8hPLUS

Metronidazole 500 mg IV q8h

http://idmp.ucsf.edu/hospitalized-adults-gastrointestinal-infections-secondary-peritonitis

Case• Pt undergoes biliary drainage procedure and is

recovering uneventfully

• How long to continue abx?

Abx duration

• If complicated infection (perforation, phlegmon), abxfor 4 – 7 d “unless unable to achieve adequate source control” – How short can you go?

• Consider longer duration + reimaging / cultures + change abx if poor clinical response, or in more complex hosts (immunocompromised, etc)

STOP-IT: Study To Optimize Peritoneal Infection Therapy

• Open-label multicenter randomized trial of 518 patients with complicated intra-abdominal infection

• Source control intervention was carried out (surgery or drainage)– Not well specified in study

• Control group: Abx until 2 d post resolution of fever, WBC < 11K, resumption of PO diet.

• Experimental group: 4 d Abx after source control procedures

• Primary outcome: composite of surgical site infection, recurrent intra-abdominal infection, or death

• Secondary outcome: Duration of antibiotic therapySTOP-IT trial. Sawyer, et al. N Engl J Med. 2015;372(21):1996

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STOP-IT Results

• No difference in composite primary endpoint – 21.8% of experimental group vs. 22.3% control (p =

0.92)

• Duration of abx 4 d vs 8 d (p = <0.001)

• Adherence to protocol 82% experimental vs 73% control

Conclusion: For patients who achieve source control procedure, 4 days of abx adequate

STOP-IT trial. Sawyer, et al. N Engl J Med. 2015;372(21):1996

Enterococcus – when to cover in HA• Definitely: positive blood cultures• Maybe: Enterococcus recovered in abd fluid cultures in HA

infxn• Per IDSA, strongly consider in:

- Immunocompromised patients- Health care-associated postoperative peritonitis- Severe sepsis who have previously received cephalosporins

and other broad-spectrum antibiotics selecting for Enterococcus species

- Valvular heart disease or prosthetic intravascular material (risk of endocarditis)

• Do NOT need to empirically cover VRE unless high index of suspicion

Role of MRSA

• Quite rare in CA intra-abd infections – guidelines do NOT recommend empiric coverage

• Per IDSA: “Empiric antimicrobial coverage directed against MRSA should be provided to patients with health care–associated intra-abdominal infection who are known to be colonized with the organism or who are at risk of having an infection due to this organism because of prior treatment failure and significant antibiotic exposure”

• Would consider adding anti-MRSA coverage in HD unstable patients (treat as per sepsis guidelines)

Role of Yeast

• C. albicans found in ∼20% of patients with acute perforations of GI tract

• Does not always need to be treated• Definitely treat:

- Positive blood cultures- Immunocompromised patients- GI perforation on PPI- Postoperative infection- Recurrent intra-abdominal infection

• Consider in: – Pancreatitis surgery (empirically)– Heavy growth from intra-op cultures

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Anti-fungal Rx

• C. albicans: fluconazole• Rising rates of non-albicans Candida (C. glabrata, C.

krusei, etc) à for HD unstable patients, use echinocandins until yeast ID is known

• C. parapsilosis, C. lusitaniae, C. guilliermondii, C. orthopsilosis have decreased susceptibility to echinocandins!

A word on pancreatitis

• 80% of pancreatitis recover within 1 wk – Abx are NOT recommended for acute pancreatitis (mild or severe)

• 20% develop necrotizing pancreatitis - roughly one-third of these will develop superinfection (high mortality)

• Dx: Clinical deterioration or lack of improvement after ~10 days of supportive care. FNA for dx/micro recommended.

• Rx: controversial – empiric antibiotics vs targeted therapy via FNA/drainage vs necrosectomy

• Often involves multiple procedures

• Length of Rx by clinical improvement

Diverticulitis• Rates of diverticulitis are increasing• Seeds,nuts, popcorn NOT contributory• Simple

– Can be managed as outpatient (Cipro/flagyl or Amp/clavulanate– May not need abx

• Complicated: T>101.5, Elev WBC, co-morbidities, IC, unable to tolerate PO’s– CTX/metronidazole, b-lactam/b-lactamase inhib, meropenam

• Surgical management– Emergent surgery (acute peritonitis/sepsis)– Urgent surgery (fails medical or percutaneous management) – Elective surgery (>3 episodes)

• Abx routinely used for outpatient management – Limited data from randomized trials suggest Abx may not be necessary

14-20%

Good summary in Young-Fadok, NEJM, 2018

Appendicitis: APPAT trial

• 530 patients w/uncomplic appendicitis randomized to open APPY vs Abx – ertepenam x 3 d, Levo+flagyl x 7 d

• At 1 yr, 70 additional pts underwent APPY– 2 w/ complicated APPY,

• 30 addnl pts underwent appy between yrs 1-5• Complication rate higher in surgical pts– 25.5% vs 6.5%– No difference in LOS but more sick leave in APPY pts

• Likelihood of recurrence in APPY group 39%

Salminen, JAMA 2018; JAMA 2015

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Consistent principles• Prophylactic abx (< 24 hrs duration)– Traumatic injuries repaired within 12 hrs– Intra-op contamination – Acute perfs of stomach, duodenum, proximal jejunem in

absence of antacid therapy or malignancy– Uncomplicated acute appendicitis

• Treatment abx (>24 hrs):until resolution of clinical signs of infxn– STOP-IT study: or 4 days, if adequate source control

• W/u if no response after 5-7 d of rx• enterococcus, yeast only need to be treated in

specific situations