Suad AL-Sulimani R3

Introduction :

in the acute setting of the emergency department (ED), it is often necessary to make treatment decisions of infection without precise knowledge of infectious source or microbial species

In certain cases (e.g., suspected meningitis, gram-negative sepsis, bacterial peritonitis, pneumonia), early empiric therapy may be lifesaving.

Unnecessary use of Antibiotics in ED contribute in emerging new antimicrobial resistance

Outline

Basic knowledge of Antimicrobial Spectrum of activity .

Discuss the indications of frequently used antibiotics in Emergency .

Antibiotics guideline use in (UTI ,Meningitis , CAP & soft tissue infection )

Evidence based Advances in Early ED Antibiotic use .Review the most common drug interactions of the

most commonly used Antibiotics

Gram +ve bacteria

• Cocci : =Strept: pyogen ,pnumoniae , viridans =Staph : aureus ,epidermus , saprophyticus

• Bacilli : =clostridium =Bacillus = Listeria

Gram -ve bacteria

• Cocci : = Neisseria gonorrhea , Niesseria Meningitidis

• Bacilli : =Klebsella , Ecoli , Enterobacter ,Psudomonus aerogenosa

• CoccoBacilli : = H.influenzae , B.Pertussis

Spectrum of Activity

Narrow-Spectrum Antimicrobial Wide-Spectrum Antimicrobial

`StRept

enterococcus

Staph .aeru

MRSA

H.Influ morexella

niesseria Psudomonus

Gram –ve rodse.coli

anaerob

PenicillinAmoxacillin/Ampicillin

+ + 0 0 +/- 0 +(niesseria meningitis

0 0 0

Amoxicillin/calvu(oral

+ + + 0 + + + 0 + +

Tazobactaum /Pipracellin (iv )

+ + + 0 + + + + + +

Carbapenums (imepenumeropenum

+ + e.fecalis only

+ 0 + + + + + +

`cephalosporins strpto

coccus

enterococcus

Staph .aerus

MRSA H.influ morexella niesseria

Psudomonus

Gram –ve rods ecoli

1st generationCephalexin

+ 0 + 0 + not cephalexin

+/- 0 0 0

2nd generationCefuroxime , cefacolr

+ 0 + 0 + + cefacolr +/-

+/- 0 +/-

3rd generation Ceftriaxone,cefexime

+ 0 + 0 + + + +/- +

3rd generation (antipsudomonus Ceftazidine

+ 0 +/- 0 + + +/- + +

4th generationcefepime

+ 0 + 0 + + + + +

*/Common antibiotics Spectrum of activities

Macrolides (bacteriostatic) - Erythromycin (also azithromycin, clarithromycin)

Gram-positive bacteria, Mycoplasma, Legionella

Aminoglycosides (bactericidal) Streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin and neomycin (topical)

gram-negative and some gram-positive bacteria. They are not useful for anaerobic bacteria,

Tetracyclines (bacteriostatic) Tetracycline, minocycline and doxycycline

b. Spectrum of activity - These are broad spectrum antibiotics and are useful against intracellular bacteria

Chloramphenicol, lincomycin, clindamycin (bacteriostatic)

Chloramphenicol - Broad rangeLincomycin and clindamycin - Restricted range

Quinolones - nalidixic acid, ciprofloxacin, oxolinic acid (bactericidal)

Gram-positive cocci , gram –ve bacteria

Oral Quinelones• Flouroquinolones (cont.).

– Trovafloxacin.– Covers Gm pos, neg, and anaerobes.– Hepatotoxicity with prolonged use. Absorption delayed by

morphine.

– Moxifloxacin.– Covers Gm pos, neg, and anaerobes.– Good vs. Clostridium and Bacteroides – same range as

metronidazole, and superior to clindamycin.– QD dosing.

– Gatifloxicin.– Covers Gm pos, neg, and anaerobes.– Very similar to moxifloxacin, but less expensive.– QD dosing.

Urinary tract infection

CYSTITIS & UTI• COMMON ORGANISM :

- 80-85% E.COLI - 5-1-% STAPH SAPROPHYTICUS -KLEBSIELLA & POTEU CAUSE

MINORITY OF CASE

CHARACTER OF PATIENTS

SUGGESTED NTIBIOTIC DURATION

oUncomplicated acute bacterial cystitis

1)Trimethoprim-sulfamethoxazole or trimethoprim.(IA)2)Fluoroquinolones, ofloxacin(IA), norfloxacin,(AII ciprofloxacin,AIIand fleroxacinAIInitrofurantoin,)3)b-lactams (E,I).

3 DAYS

3-7 DAYS

Evedience based advances :Most of the b-lactams appear to be less effective may yield increased incidences of recurrences and of adverse effects. Amoxicillin is thus no longer recommended as empirical therapy for uncomplicated UTI

(the sanford guide for antimicrobial therapy 2010)

o Antibiotic therapy for three days was similar to prolonged therapy (≥5 days) in achieving symptomatic cure, while prolonged treatment was more effective in obtaining bacteriologic cure.

oThere is no apparent benefit in extending therapy with TMP-SMX or a fluoroquinolone past three days, and adverse reactions are more common in patients treated with longer regimens.

CHARACTER OF PATIENTS

SUGGESTED NTIBIOTIC DURATION

oUncomplicated acute pyelonephritis Resistance of E. coli to TMP/SMX 13-45% in collaborativeER study (CID 47:1150, 2008).

1)oral fluoroquinolone , Levo750 mg q24, Oflox 400 mgbid, Moxi NAI 400 mg q24h(A,II).2) CIP 500 mg bid or CIP-ER(AII)1000 mg q24hpossiblyIf a gram-positive bacteriumis the likely causative organism, amoxicillin oramoxicillin/clavulanic acid may be used alone (B,III)

2 weeks

7 days

Evedience based advances :In randomized double-blind trial, bacteriologic and clinical success higher for 7 days of CIP than for 14 days of TMP-SMX; failures correlated with TMP-SMX in vitro resistance.Since CIP worked with 7-day rx, suspect other FQs effective with 7 days oftherapy; Levo 750 mg FDA-approved for 5 days

(the sanford guide for antimicrobial therapy 2010)

• Common organisms: -Enterobacteriaceae, -P. aeruginosa, enterococci -rarely S. aureus

CHARACTER OF PATIENTS

SUGGESTED NTIBIOTIC DURATION

Complicated UTI/cathetersObstruction, reflux, azotemia,transplant, Foley catheterrelated,R/O obstruction

(AMP + gent) or PIP-TZ (Tazocin ) orTC-CL ticarcillin-clavulanateor or IMP= imipenem- or MERmeropenem (IV FQ: CIP, Gati, Levo) orCeftaz or Cef

2-3weeks

(CID 42:46,2006)

Community Acquired Pneumonia (CAP)

Common organisms in CAP

No co-morbidity: Most common organism strept.pnumonae 2/3 of the cases ,Atypicals—M. pneumoniae,, viral

Co-morbidity:• Alcoholism: S. pneumo,anaerobes, coliforms• COPD: H. influenzae,M. catarrhalis, S. pneumo• IVDU: Hematogenous S. aureus• Post-CVA aspiration: Oral flora, incl. S. pneumo• Post- influenza:S. pneumo. And S. aureus

oPreviously healthy and no risk factors for drug-resistant S. pneumoniae (DRSP) infection

A macrolide (azithromycin, clarithromycin, orerythromycin) (strong recommendation; level Ievidence) Doxycycline (weak recommendation; level IIIevidence)

Evidence based advances :There is abundant evidence that macrolide monotherapy is highly effective in the treatment of CAP in outpatients with mild to moderately severe disease For patients admitted through the emerg dose should be administered while still in the ED .(Moderate recommendation; level III )

Clinical Infectious Diseases 2000;31:383–421 © 2000 by the Infectious Diseases Society of America.

oPresence of comorbidities, - chronic heart, lung,liver, or renal disease- diabetes mellitus; ---alcoholism; malignancies;asplenia; immunosuppressing use of immunosuppressing drugs; use of antimicrobials within the previous 3 months (in which case an alternativefrom a different class should be selected)

A respiratory fluoroquinolone (moxifloxacin, gemifloxacin,or levofloxacin (level I evidence)

A b-lactam plus a macrolide (strong recommendation (level I evidence)

alternatives include ceftriaxone,cefpodoxime, and cefuroxime [500 mg 2times daily]; doxycycline [level II evidence]

oRespiratory fluoroquinolones (levofloxacin, moxifloxacin or gemifloxacin were more likely to result in treatment success than the combination of a beta-lactam plus a macrolide for the treatment of CAP that was mostly mild to moderate in severity (odds ratio, OR 1.39, 95% CI 1.02-1.90)

Bacterial Meningitis

Empiric Therapy—immunocompetent

Age: Preterm to <1 mo

Group B strep 49%,E. coli 18%, listeria 7%,

AMP + cefotaxime AMP + gentamicin

Age: 1 mo– 50 yrs S. pneumo, meningococci,H. influenzae now very rare,listeria unlikely if young &immuno-competent (addampicillin if suspect listeria:2 gm IV q4h)

Adult dosage: [(Cefotaxime2 gm IV q4–6h ORceftriaxone 2 gm IV q12h)]+ (dexamethasone) +Vanco[(MER 2 gm IV q8h) (Peds:40 mg/kg IV q8h)] + IVdexamethasone + vanco

Age > 50 years or alcoholism or other deblitating illneesses , immunocompromized

Strpt .Pnumoniae,listeria, gram –ve bacilli

1)AMP 2 gm IV q4h) +(ceftriaxone 2 gm IV q12hor cefotaxime 2 gm IV q6h)+ vanco + IVDexamethasone2) MER 2 gm IV q8h + vanco +IV dexamethasone.

Basilar skull fracture S. pneumoniae, H. influenzae, group A beta-hemolytic streptococci

Vancomycin plus a third-generation cephalosporin•Δ

Penetrating trauma

Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic gram-negative bacilli (including Pseudomonas aeruginosa)

Vancomycin plus cefepime; OR vancomycin plus ceftazidime; OR vancomycin plus meropenem

Delay in initial antibiotics in the emergency department (median delay of four hours) was associated with a worsening of hypotension, altered mental status, and seizures in about 15 percent of patients. Those patients whose delay in antibiotic therapy allowed their disease to advance from having zero or one to having two or three poor prognostic indicators had a significant increase in adverse outcomes.

o patients with pneumococcal meningitis, a delay in antibiotic treatment of more than three hours after hospital admission was a strong and independent risk factor for mortality (OR 14.1; 95% CI: 3.9 to 50.9). Delayed therapy was a greater risk factor than the isolation of a penicillin-resistant strain (OR 6.83; 95% CI 2.94-20.8) or a higher disease severity (OR 1.12; 95% CI 1.07-1.15)

Fever Interval before Diagnosis, Prior Antibiotic Treatment, and Clinical Outcome for Young Children with Bacterial Meningitis

Clinical Infectious Diseases 2001;32:566–572

• retrospective chart review, we compared the fever interval that preceded diagnosis with the complication rate among 288 young children (age, 3–36 months)

• Pneumococcus species were associated with the longest fever interval prior to diagnosis of meningitis, the highest frequency of contact with a clinician before hospitalization, and the highest rate of documented morbidity or mortality. For S. pneumoniae, there was an association between antibiotic treatment received at prior meetings with a clinician and a reduced rate of meningitis related complications (odds ratio, 0.14; ). ‐ Antibiotic treatment during such meetings is associated with a substantial reduction in disease related ‐sequelae.

• Skin and Soft-Tissue Infections intheEra of Resistance: MRSA and More

CA-MRSA: The New Epidemic• A global emerging health problem 8-12% of MRSA infections• Most involve skin & soft-tissue structures• Commonly presents with spontaneous abscess• Reported in severe infections: Bacteremia, Pneumonia (often necrotizing)Osteomyelitis Bursitis, arthritis,Meningitis

Fridkin SK, et al.N Engl J Med. 2005;352:1436-1444.Pannaraj PS, et al.Clin Infect Dis. 2006;43:953-960.

Risk factors to develop CAMRSA soft tissue infection : = Antibiotic use (particularly cephalosporin and fluoroquinolone use) strongly correlates with the risk for MRSA colonization and infectio =residents of long-term care facilities =Homeless =IV drug users =Prisoners =Military Personnel =HIV patients

60% are abscess, 40% cellulitis , small persentage as impetigo

Clin Infect Dis. 2007;45 Suppl 3:S171-6

Antibiotics & Abscesses

• - Not required for simple, uncomplicated cases - Indications for addition of antibiotics: Major surrounding cellulitis Signs of systemic toxicity Facial abscess Immunocompromised Recurrent abscesses Large abscess (≥ 5 cm) - Typical duration: 7-10 days

The Sanford Guide: 2008, page 47. Lee MC, et al. Pediatr Infect Dis J. 2004;23:123-127.

Ruhe JJ, et al.Clin Infect Dis. 2007;44:777-784.

Skin and soft tissue infections

Parenteral therapy

• Vancomycin (30 mg/kg IV every 24 hours in 2 equally divided doses; not to exceed 2 g/24 hours unless concentrations in serum are inappropriately low)

• Daptomycin (4 mg/kg IV once daily)• Linezolid (600 mg IV twice daily)• Tigecycline (100 mg IV once, thereafter 50 mg IV every 12 hours)

Oral therapy

• TMP-SMX (2 double-strength tablets orally twice daily)• Doxycycline or minocycline (100 mg orally twice daily)• Clindamycin* (300 to 450 mg orally every 6 to 8 hours)

• Linezolid (600 mg orally twice daily)

•Sepsis

oCutoff time of <1 hr for early goal directed therapy & administration of appropriate antibiotics in severe sepsis & septic shock initiated in emergency department are primary determinant of mortality.

Effectivness of Antibiotic administration within 1 hr of hypotension was associated with better survival rate in septic

shock

Antibiotics in sepsis

if Pseudomonas is an unlikely pathogen vancomycin with one of the following:Cephalosporin, 3rd or 4th generation (eg, ceftriaxone or cefotaxime)orBeta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanateorCarbapenem (eg, imipenem or meropenem

+Pseudomonas is a possible pathogen, we combine vancomycin

• Antipseudomonal cephalosporin (eg, ceftazidime, cefepime, or

• Antipseudomonal carbapenem (eg, imipenem, meropenem), or

• Antipseudomonal beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam,ticarcillin-clavulanate), or

• Fluoroquinolone with good anti-pseudomonal activity (eg, ciprofloxacin), or

• Aminoglycoside (eg, gentamicin, amikacin), or• Monobactam (eg, aztreonam)

Common antibiotic drug interaction

Take home massages

• Basic knowledge of antibiotic spectrum of activity is required for infection management

• Advances in UTI treatment support using antibiotics for shorter course

• Oral Flurquinelones are supported by evedience to be effective in treatment of CAP

• Early AB in meningitis is proven to reduce complications & improve outcome

Take home massages

• MRSA soft tissue & wound infection is a newly emerging problem

• Early Antibiotics in sepsis is part of early goal directed therapy

THANK YOU

• Pregnancy Aerobic Gm-neg. bacilli &• Staph. hemolyticus• Screen 1st trimester. If positive, rx 3–7 days with amox,• nitrofurantoin, O Ceph, TMP-SMX, or TMP alone• Screen monthly for recurrence. Some authorities treat

continuously until delivery• (stop TMP-SMX 2 wks before EDC). ↑ resistance of E. coli

to TMP-SMX.• Before and after invasive urologic• intervention, e.g., Foley• catheter• Aerobic Gm-