infections of the midsection - ucsf cme · 2020-02-11 · yeast • critically ill plus ugi source...

Infections of the Midsection

Sarah Doernberg, MD, MASAssociate Professor, Division of Infectious DiseasesMedical Director of Adult Antimicrobial Stewardship

Disclosures

Consultant: Genentech, Basilea Pharmaceutica

Outline

General principles of intraabdominal infections

Medical management of appendicitis

Medical management of diverticulitis

Pyogenic biliary diseases

ABCs of hepatitis

If you take home one thing…

When there is pus under pressure, there is one person to call (and it is not me!)

Case #1. 66 year-old F with hypertension, DMII, and depression admitted from home with diverticulitis with microperforation. She is febrile to 39 degrees but other vital signs are stable. What antibiotic would you chose and why?

A. Piperacillin/tazobactam

B. Ertapenem

C. Ceftriaxone + metronidazole

D. Ampicillin/sulbactam

What to take into account when selecting antibiotics

Source (community vs healthcare system)

Site of infection

Host factors: Severity of illness, age, comorbid conditions, nutritional status, travel history

Source control achieved?

If high-risk CA-IAI (host factors, poor source control) or HA-IAI, opt for broader coverage

Low-mod risk CA-IAI High-risk CA-IAI HA-IAI

Microbiology of IAIsOrganism Example CA-IAI HA-IAI

Enterobacteriaceae E. coli

Strep spp. Strep milleri grp

Glucose NF P. aeruginosa

Anaerobes B. fragilis

Enterococci

S. aureus

Yeast

• Green = very common

• Yellow = common

• Orange = uncommon

• Red = rare

Bottom line:• Low to moderate CA-IAI = ceftriaxone + metronidazole• High-risk CA-IAI or HA-IAI = piperacillin/tazobactam (mero if critically ill)

Mazuski et al. Surg Infect (Larchmt). 2017 Jan;18(1):1-76. doi: 10.1089/sur.2016.261; Solomkin JS et al. Clin Infect Dis, 50(2):2010, Pages 133–164, https://doi.org/10.1086/649554.

A simplified GNR scheme

Need for Pseudomonas aeruginosa coverage?

Nee

d f

or

ES

BL

co

vera

ge?

No YesNo Ceftriaxone

(+/- metronidazole)Piptazo or cefepime/metro

Yes Ertapenem Meropenem

When should I add empirical IAI coverage for…?

Yeast

• Critically ill PLUS UGI source

• Recurrent bowel perf• Heavy colonization and

HA-IAI• Surgically-treated

pancreatitis

Enterococcus

• HA-IAI PLUS one of:• post-operative, prior

cephalosporin use, immunocompromised, prosthetic material

• VRE: liver transplant with hepatobiliary source

MRSA

• Critically-ill• Consider if colonization

or known risk factors

Review recent microbiologyIf isolated on cx, most of the time should cover above organisms

Mazuski et al. Surg Infect (Larchmt). 2017 Jan;18(1):1-76. doi: 10.1089/sur.2016.261; Solomkin JS et al. Clin Infect Dis, 50(2):2010, Pages 133–164, https://doi.org/10.1086/649554.

• Double-blind RCT• 19 ICUs in France• Sepsis after ≥ 4d abx• Colonized w/ candida• CVC or arterial line• ~25% surgical pts• N = 260 patients

Micafungin(mITT = 128)

Placebo(mITT = 123)

14 days

68%

60%

HR 1.53 (0.87-2.08)

28d IFI-free survival

Surgical HR: 1.6 (0.7-3.7)Overall survival did not differ

Timsit J-F et al. JAMA. 2016;316(15):1555-1564. doi:10.1001/jama.2016.14655

Case #1, con’t. You initiate ceftriaxone and metronidazole. She initially defervesces but on HD4 spikes a temperature to 38.5 and notes her abdominal pain has returned. Her vital signs remain stable and she has some mild tenderness in her lower abdomen but no surgical signs. Her WBC goes from 913. What should you do next?

A. Broaden her antibiotics to meropenem and vancomycin

B. Pan-culture, get a chest xray, get a CT scan, and check stool for C. diff

C. Both A + B

What should you consider when someone is not responding to antibiotics? Lack of source control

Resistant infection

Complication of infection

New nosocomial complication

Drug reaction, other noninfectious etiology

Results

CXR: Edema

UA: >50 WBCs, +LE, +nitrites

Urine culture: > 100,000 VRE

Blood culture: Negative

C. difficile: Negative

CT abdomen: 5x7cm abscess abutting desc colon, no free air

IR places a drainage catheter. How long will you continue antibiotics?

• Open-label RCT• N = 518 patients• Noninferiority (10%)• Complicated intra-

abdominal ifxn• Intervention for source

control

Abx until 2+ ddafter recovery

4 days abx

Source control(median 8 days)

(median 4 days)

Sawyer RG et al. N Engl J Med 2015; 372:1996-2005. DOI: 10.1056/NEJMoa1411162

21.8%

22.3%

Diff: -0.5% (-7.0 to 8.0%)

SSI, recurrence, death

No ▲ mortality↓t to dx of SSI or recurrence

Case #2. Which of the following scenarios should be managed initially with antibiotics alone? A. Non-perforated appendicitis

B. Perforated appendicitis with RLQ phlegmon

C. Perforated appendicitis with RLQ abscess

D. Perforated appendicitis with septic shock

Diagnosis of appendicitis

H+P: Migration of pain to RLQ, vomiting most suggestive

Alvarado score: Identify patients at low-risk (<4), can avoid imaging

Imaging: CT beats ultrasound(u/s for kids, pregnancy (or MRI) or as screening)

Flum DR. N Engl J Med. 2015 May 14;372(20):1937-43. doi: 10.1056/NEJMcp1215006 ;

“Antibiotics first” for uncomplicated appendicitis?IV abx x 1-3 days, then PO to complete 10-day course

One study found that abx may not even be necessary! Are we overdiagnosing?

-Some will avoid surgery

-Good option if prior surgical complications, phobia, poor candidate, equivocal picture

-30% recur

-May miss cancer

-CT can miss complications

-Fecolith pts should have surgery

De Savioro S et al. World J Emerg Surg. 2016 Jul 18;11:34. doi: 10.1186/s13017-016-0090-5; Flum DR. N Engl J Med. 2015 May 14;372(20):1937-43. doi: 10.1056/NEJMcp1215006; Park HC et al.Br J Surg. 2017;104(13):1785

Bottom line = patient-centered decision

Complicated appendicitis management

• Antibiotics alone for phlegmon (7-10 d IVPO)• Percutaneous drain preferred for abscess• Interval appy if persistence or recurrence• Colonoscopy to evaluate for neoplasm if > 40

Phlegmonor abscess

• Appy recommended• 4 days of post-operative abx reasonableSepsis

De Savioro S et al. World J Emerg Surg. 2016 Jul 18;11:34. doi: 10.1186/s13017-016-0090-5

Moving right to left

General principles

Appendicitis

Diverticulitis

Pyogenic liver and biliary diseases

ABCs of hepatitis

Diverticulitis occurs on a spectrum

Uncomplicated

-Outpatient rx unless at risk

-7-10 dd abx-FQ or TMP/SMX

PLUS metronidazole-Amox/clavulate

-Omit abx?Needs close f/u

Uncomplicated, at risk

-Microperforation-Sepsis/severe dz

-Comorbidities-Advanced age-Failed initial rx

-Cannot take POInitial inpt rx (abx

dur +/-10 dd)

Complicated

-Frank perforation-Abscess

-Obstruction-Fistula

-Recurrences

Stollman N et al. Gastroenterology 2015; 149:1944-49; Francis NK et al. Surgical Endoscopy 2019; 33: 2726-2741

Diagnosis of diverticulitis

H+P

• LLQ pain and TTP• Absence of emesis• Minority w/ RLQ pain

Studies

• CRP usu > 50• CT is the best

modality• Alterative: u/s

Hinchey classification

• 0 : mild clinical• 1a: colonic reaction

with phlegmon• 1b: pericolic or

mesenteric abscess• II: intra-abdominal or

RP abscess• III: purulent peritonitis• IV: feculent peritonitis


What dietary advice should I give?

Popcorn/nuts/seeds are ok

Uncomplicated dzok to eat, consider initial bowel rest

Eat a high-fiber diet

Long-term


Acute management

Complicated dzclears vs bowel rest

No antibiotics for uncomplicated diverticulitis?Swedish experience

Chabok A et al. Br J Surg. 2012 Apr;99(4):532-9. doi: 10.1002/bjs.8688

Abx (IVPO) x 7d

IV fluids aloneUncomplicateddiverticulitis

6/309 (1.9%)

p = 0.3

3/314 (1.0%)

No diff LOS or recurrence

complications

Limitations:-Unblinded-Patients were treated in the hospital initially

No antibiotics for uncomplicated diverticulitis?Dutch experience

Daniels et al. Br J Surg. 2017 Jan;104(1):52-61. doi: 10.1002/bjs.10309

Amox/clav x 10 dd

Supportive careHinchey 1a or 1bdiverticulitis

7/266 (2.6%)

p = 0.2

10/262 (3.8%)

Observation: ↓LOS

6 mo complications

13% outpatient

Limitations:-Unblinded-Trend towards increased readmissions-Not powered for Hinchey 1b subgroup

Who should have surgery?

Acute complications• Frank perforation with peritonitis• Abscess

• Percutaneous drainage ok, controversy around need for future elective surgery• Medical management for small abscesses ok

• Obstruction (c/f cancer)• Fistula

Chronic complications• Smoldering diverticulitis (sxs can persist up to 6 mths, distinguish from IBS)• High-risk for severe recurrence (i.e. immunocompromised, prior abscess)• Recurrent disease requires individualized discussion of risks/benefits


When is colonoscopy indicated?

There is an association between colon CA and diverticulitis- Colon CA even more common in those with abscess (6.7x),

perforation (4x), and fistula (18x)

In general, screening recommended unless pt has recently had screening within 1 year

Typically 6-8 weeks after resolution

Lau KC et al. Dis Colon Rectum. 2011 Oct;54(10):1265-70. doi: 10.1097/DCR.0b013e31822899a2.

Shifting gears…

General principles

Appendicitis

Diverticulitis

Pyogenic biliary diseases

ABCs of hepatitis

Case #3. 46 year-old F presents with severe RUQ pain x 15 hours. She has a temp of 38.5; other vitals are stable. On exam, she has RUQ tenderness and guarding. Labs have been obtained and are pending. What is the next step in evaluation?A. Abdominal CT scan

B. HIDA scan

C. Ultrasound

D. No imaging study is necessary; she can proceed straight to surgery

Pathophysiology of calculous cholecystitis

Strasberg SM. N Engl J Med 2008; 358:2804-2811. DOI: 10.1056/NEJMcp0800929; Muira F et al. J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):31-40. doi: 10.1002/jhbp.509

Obstruction (stone)Sterile

inflammation

Secondary infection

Necrosis, gangrene,

emphysema

Perforation, abscess, peritonitis

Mild (I) Mod (II) Severe (III)

Inflammation without organ dysfunction

WBC > 18, RUQ mass, sxs > 72h, marked local inflammation

End-organ dysfunction

What is the best timing for intervention?

Laparoscopic cholecystectomy is the treatment of choice

Rationale for early surgery: - Longer amount of inflammationtechnically harder surgery

- 30% of pts will have recurrence @ 1 year

Ansaloni L et al. World J Emerg Surg 2016; 11:52; Wu, x-D et al. Brit J Surg 2015; 102(11):1302-13. https://doi.org/10.1002/bjs.9886

Early Late

Recovery

LOS

Surgical complications

SSI

If > 10d from symptom onset, delay surgery to 45 daysCommon bile duct stones should be sought and removed before, during, or after surgery

What if your patient is a poor surgical candidate?

Antibiotics and supportive care for all!

Most should have drainage:- Percutaneous cholecystomy tube for most

- Endoscopic approaches also possible

CHOCOLATE trial:

Loozen CS et al. BMJ. 2018 Oct 8;363:k3965. doi: 10.1136/bmj.k3965.

APACHE 7-15

Lap chole (N = 66)

PTDB (N = 68)

Random

ize

Death Complication

Lap chole 3% 12%

PTBD 9% 65%

P-value 0.27 <0.001

<24 hours

A word on acalculous cholecystitis

10% of cholecystitis caseshigh morbidity/mortality- Gallbladder stasisischemia

- Many risk factors: Immunocompromise, critical illness, anatomic

Insidious presentation (e.g. unexplained fever)

Give antibiotics plus:- Cholecystectomy OR

Indications: necrosis or perforation, emphysematous cholecystitis

- Percutaneous drainage if too unastable or not meeting indications

If fails, proceed to surgery

Suppurative infection take-home

Most importantly: Control the source of infection- Intervene early for uncomplicated appy or cholecystitis

- Intervene for majority of complicated disease

- Stop antibiotics shortly after source control

Appendicitis, diverticulitis, and cholecystitis are all mostly inflammatory diseases

Antibiotic choice differs by community vs. hospital acquisition and patient-specific risk factors

Shifting gearsA, B, Cs of hepatitis

Hepatitis A

Hepatitis B

Hepatitis C

Which of these patients should receive HAV immunization?

A. A healthy 6 month-old infant

B. A 25 year-old F who works at a day care center

C. A 55 year-old M who works in a burrito shop

D. A 40 year-old F adopting an infant from Ethiopia

E. A 33 year-old M working in a sewage treatment plant

HAV prevention

Hyg

iene • Spread via

fecal-oral route• Food/H20

precautions• Sanitation V

acci

ne • Kids > 1 yo• Travel• MSM• Homeless• Drug use• Clotting factors• Chronic liver dz• Adoption

Pas

sive

imm

unity • Pre-travel

• @ risk < 2wk• Can’t get

vaccine• Post exposure:

• Older age (>40!)

• Allergy• IC

https://www.cdc.gov/hepatitis/hav/havfaq.htm#general

Vaccine: lasts 20yInfection: lifelong immunity

CDC has great FAQs

HBV case

New couple seeking care in your office

39 year-old M, no medical issues

- Born in US, parents emigrated from Mongolia

- Does not know immunization history

35 year-old F

- Severe RA failing therapy, rheumatologist planning rituximab

- Born in the US to US-born parents

No risky behaviors

B. Schwartz

Case #4, con’t. Which patient will you screen for HBV?

A. Male

B. Female

C. Both patients

D. Neither patient

Who to screen (HBsAg)

High prevalence area- Born in regions with HBsAg prevalence ≥ 2%

- Born in US to parents from area with HBsAg prevalence ≥ 8%, if unvaccinated

- Born to HBsAg + mothers

High-risk activities- IDU, MSM, household contacts, sexual contacts

Prevention of transmission- Organ/blood/tissue donors, hemodialysis patients, pregnancy, needlestick

Risk of reactivation - Immunosuppression (test for HBcAb and HBsAb as well)

- HIV, HCV

Male

Female

Weinbaum CM et al. MMWR 2008; 57(RR08);1-20. https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5708a1.htm

HBV natural history

Acute HBV infection with recovery

Window period


Chronic HBV


Isolated HBcAb+

1. False positive

2. Passive txsfer from maternal antibodies or IVIGNo action

3. Resolved infection with very low-level HBsAb

4. Window period/recovery fr acute infection (not yet made sAb)

5. Occult chronic HBV with undetectable HBsAg

https://www.cdc.gov/hepatitis/hbv/pdfs/serologicchartv8.pdf

How to sort this out:• Check HBV DNA#5 (not always +)• Repeat testing in 6 mths (addresses #2, #4)• Can also immunizeresponse suggests #1; if not, #3

Case #4, con’t: Which patient should receive HBV treatment?

A. Male

B. Female

C. Both

D. Neither

Which adults to treat

1. Immune-active:- HBeAg neg: HBV DNA > 2000 + (ALT > 2 ULN or +histology)

If not meeting criteria: Case-by-case basis

- HBeAg pos: HBV DNA > 20,000

2. Cirrhosis + HBsAg

3. Pregnancy + HBsAg + DNA > 2K

4. Acute HBV-mediated decompensation

5. Immune suppression, HIV, HCV Rx planned

HCC screening (u/s +/- AFP) recommended for certain populations (see reference slide)

Male

Female

Terrault NA et al. Hepatology 2016; 63(1):261-283

Prevention

Behavioral modification

Immunization (recombinant HBsAg): Prevention & PEP

- Single Ag and combos available

- All kids, @ risk (sexual/blood/fluid exposure), comorbidities, travel

- CDC FAQs very helpful

HBIG: 3-6 mth protection; used as PEP

- Unvaccinated or nonresponder w/ HBsAg+ exposure (+vaccine)

- Infants born to HBsAg+ mothers

- Certain transplant recipients

Mast EE et al. MMWR 2006; 55(16); https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm

Common HBV vaccination questions

Can you give doses from different manufacturers? Yes

If you get off schedule, what do you do? Proceed with next dose, no need to restart

Are extra doses or giving to someone with HBV harmful? No

Can it be given to immunocompromised patients? Yes

How long does immunity last? > 20 years

Should I screen for immunity before immunization? Yes, screen all patients in high-risk groups; no need for infants/kids

Should I send serologic tests after immunization? Only if it will change management:

https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm

• HCW• ESRD, HIV, immunocompromised

• Sexual partners• Infants of HBsAg+ moms

Case #4, con’t: 1 month after she completes her HBV vaccine series, your pt’s HBsAb is negative. What do you do next?

A. Recheck HBsAg

B. Give 1 booster dose of the vaccine

C. Give the whole series again

D. Counsel her not to receive ritux

Management of vaccine nonresponse

If received the vaccine remotely:- Up to 60% lose detectable Ab over time (though still protected)

- Challenge with 1 doseamnestic response

If recent or no response above, give 2nd three-dose series- 15-25% will respond after dose #1, 30-50% after all three

Retest 1-2 mths later

If still no response:- Check HBsAg

- Consider nonresponder (<5%)PEP if exposed

https://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html#diagnosis

Case #5

36M with well-controlled HIV, chronic HCV, and intermittent IV heroin abuse. His HCV has never been treated.

He states that he’s been clean for 8 months

Patient wonders, “Can I qualify for one of those fancy new hepatitis treatments that I keep hearing about?”

Bryn Boslett, MD

HCV pathogenesis

https://www.cdc.gov/hepatitis/hcv/hcvfaq.htm

Populations to screen

Ever injection drug use

Intranasal illicit drug use

All baby boomers (1945-1965)

HIV+

Before PrEP initiation

Hemodialysis

Incarceration

Sxs/signs of hepatitis

Transplant or transfusion < 1992, clotting factors < 1987

Transplant from high-risk donor

SOT donors

HCWs

Unregulated tattoo

Children born to HCV+mothers

At least 1 time; Screen more frequently if risk is ongoing

https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/hepatitis-c-screening

https://www.cdc.gov/hepatitis/hcv/pdfs/hcv_graph.pdf

When to check HCV RNA:• Reexposure in HCV Ab + pt• Dx of HCV in immunocompromise• Dx of active versus cleared virus

after screening Ab• Antiviral therapy

How to test

Who to treat?

Everyone with chronic HCV should be treated- Except limited life expectancy (12 mths) not reversible by treatment or

transplant

https://www.hcvguidelines.org/evaluate/when-whom

Things to know before starting

1) Degree of liver fibrosis Typically noninvasive

2) Genotype3) History of prior treatment: Failed DAAs vs older agents4) Concomitant issues

-Comorbid conditions (incl HBVreactivation risk)-Medications (drug-drug interactions, esp ARVs PPIs)

Bryn Boslett, MD

Insurance requirements and pill burden may also play a role in choice of regimen

What you need to know about genotypes

Messina JP et al. Hepatology. 2015; 61(1): 77–87.

• 7 genotypes• Many subtypes• Affects prognosis & Rx• GT1: 70% of US HCV

• 55% 1a• GT2: 15-20%• GT3: 10%

• Fibrosis progression• Remainder: Uncommon

NS5a NS5b Protease

Target Viral assembly and release Viral RNA polymerase Viral protease

Naming “-asvir" “-buvir” “-previr”

Harvoni Ledipasvir Sofosbuvir

Zepatier Elbasvir Grazoprevir

Epclusa Velpatasvir Sofosbuvir

Mavyret Pibrentasvir Glecaprevir

Vosevi* Velpatasvir Sofosbuvir Voxilaprevir

* = for treatment-experienced (including with NS5a inhibitors)

What are the options?

Kohli A et al. JAMA 2014;312(6):631-40. doi: 10.1001/jama.2014.7085.https://www.hcvguidelines.org/evaluate/resistance Bryn Boslett, MD

Hepatitis C resources

https://www.hcvguidelines.org/

https://www.hep-druginteractions.org/

https://www.hepatitisc.uw.edu/

Hepatitis take-home

Prevention is key

Be aware of who to screen, vaccinate, and treat

Know where to find useful resources

HBV serologiesHBsAg HBsAb HBcAb IgM Total HBcAb HBV VL Interpretation

- - - - - Susceptible

- + - - - HBV vaccinated

- + - + - “Resolved” infection

+ - + +/- +++ Acute infection

- - + +/- + Window

+ - - + ++ Chronic

+ - - +/- ++ Flare

- - - + +/- Multiple interpretations

Who w/ HBV should be screened for HCC?

Populations:- Asian M > 40 y/o, F > 50 y/o- Cirrhosis- Family history of HCC- Africans/African Americans > 20 y/o- Any > 40 y/o w/ persistent or intermittent ALT elevation

and/or HBV DNA > 2000 How to screen (similar recs for HCC screening in HCV):

- Q6mth ultrasound +/- AFP- CT is not recommendedhigh false +, radiation, cost

Heimbach JK et al. Hepatology 2018; 67(1):358-380

Treatment

Immunological cure: Loss of HBsAg & HBV DNA suppression

Virological cure: Currently impossible: covalently closed circular DNA (cccDNA) still in hepatocytescan reactivate

Drug AE Comments

Interferon Flu-like sxs, mood, cytopenias, autoimmunity Fixed duration

Lamivudine Pancreatitis, lactic acidosis Risk of resistance

Telbivudine ↑CK, lactic acidosis, neuropathy

Entecavir Lactic acidosis

Adefovir ARF, Fanconi sx, nephrogenic DI, lactic acidosis

Tenofovir Nephropathy, Fanconi sx, osteomalacia, lactic acidosis

Terrault NA et al. Hepatology 2016; 63(1):261-283

infections of the midsection - ucsf cme · 2020-02-11 · yeast • critically ill plus ugi source...

Documents