Community Acquired Bacterial Infections:

Principles of antibiotic therapy forcommon outpatient conditions

Dr K Outhoff

The scope

1. Goals of Antibacterial therapy2. Tonsillitis / pharyngitis3. Acute otitis media and sinusitis4. Community acquired pneumonia in adults5. Urinary tract infections6. Summary

Antimicrobial activity against a specific pathogen is reliant on:

• The agent penetrating to an appropriate binding site

• Attaching itself to that site in adequate concentrations

• Remaining there for a sufficiently long period to inhibit bacteria from carrying out its normal life functions

Upper and LowerRespiratory Tract Infections

Tonsillitis / pharyngitis

Bacterial sinusitis/ otitis media

Community acquired pneumonia

Acute tonsillitis / pharyngitis

Acute tonsillitis / pharyngitis

Viral 80%

• EBV • Cytomegalovirus• Adenoviruses• Measles

Bacterial 20%

• Streptococcus pyogenes (GABHS)

• Tonsillitis Acute glomerulonephritis Rheumatic Fever

Rx aimed at preventing above complications

• Pen VK given 30 minutes before food, twice daily X 10/7• Amoxicillin (rash if EBV present), no food restrictions, once or twice daily X

10/7

• Clindamycin if allergy• (Macrolide if allergy)

Short course (3-5 days) possible with co-amoxiclav, azithro, clarithro, cefpodoxime, cefuroxime

Updated guideline for the management of URTIs in South Africa: 2008: SA Fam Pract 2009;51(2):105-114

Points in favour of empiric antimicrobial treatment

• Acute onset• Temperature > 38⁰C• Tender anterior cervical nodes• Tonsillar erythema / exudates• Age 3-15 years• Previous Rheumatic -fever or -heart disease

Indications for referral

Local complications:• Peritonsillar sepsis (quinsy, cellulitis, trismus)• Recurrent infections (> 4 / year)• Non-response to initial therapy

Systemic complications:• Acute rheumatic fever• Severe systemic illness

Sinuses

Acute bacterial sinusitis / otitis media

• Aetiology: – S. pneumoniae – H. Influenzae – Moraxella catarrhalis (consider if no rapid clinical

response)

Antibiotic options for ABS1. Beta lactams:

– Amoxicillin– Amoxicillin-clavulanate– Cefuroxime*– Cefpodoxime*

2. Macrolides:– Erythromycin– Azithromycin– Clarithromycin

3. Respiratory fluoroquinolones:– Moxifloxacin– Gemifloxacin– Levofloxacin

SP Oliver. Antimicrobial agents for common outpatient conditions. Mims Disease Review 2009/2010Updated guidelines for the management of URTI in SA 2008 SA Fam Prac 2009

Rx: acute bacterial sinusitis• Analgesia• Antibiotics:

– Amoxicillin 10 days (first choice) or – Co-amoxiclav 10 days if failed therapy

– Penicilin allergy: • Macrolide• Respiratory fluoroquinolone

Acute bacterial sinusitis and otitis media*Bugs First line Second line -

No rapid response

Pen. allergy

S. PneumoniaeH. influenzae

Amoxicillin Co-Amoxiclav Moxifloxacin (Gemifloxacin)(Levofloxacin)

(Cefpodoxime)(Cefuroxime)

(Moxifloxacin) Macrolide:ErythromycinAzithromycinClarithromycin

M. catarrhalis Doxycycline

ChronicMultiple bacteria +anaerobes

Co-Amoxiclav Moxifloxacin orMacrolide

Add Metronidazole

Indications for referral

• Failure to respond after 72 hours• Peri-orbital swelling• Evidence of CNS extension (meningism, focal neuro

signs, altered level of consciousness)• Severe systemic illness• Chronic sinusitis: symptomatic > 30 days

Community Acquired Pneumonia (CAP)

CAP• Confirm diagnosis

CXR, other imaging devices

• Establish aetiological diagnosis when identification of specific pathogens will significantly alter standard (empirical) management decisions. (not routine for OPD):

– Sputum, microscopy, blood culture, sensitivity– Urinary antigen tests for Legionella, pneumococcus in

severely ill– Endotracheal aspirate in intubated patients– Antibiotic susceptibility patterns

CAP: site of care decisions• Outpatient vs Hospital

• ICU (septic shock / requiring mechanical ventilation) vs general ward

• Severity-of-illness scores help identify candidates for outpatient treatment:CURB-65 criteria: confusion, ureamia, respiratory rate, low blood pressure, age 65 or greater

• Prognostic scores:Pneumonia severity index (PSI)

CID 2007:44 (suppl 2). Mandell et al

Community acquired pneumonia empiric Rx

Bugs OPD OPD: risk factors for DRSP

Inpatient treatment ICU

TY PICAL (7-10 ) Macrolide: Respiratory fluoroquinolone:

Respiratory fluoroquinolone

Fluoroquinolone + beta lactam

Streptococcus pneumoniae +++

Azithromycin Moxifloxacin

Haemophilus influenzae

Clarithromycin Levofloxacin

Klebsiella pneumoniae

Erythromycin Gemifloxacin

Staph. aureus

ATYPICAL (14) Doxycycline Macrolide +Beta-lactam :

Macrolide + Beta-lactam

Azithromycin+Beta-lactam

Legionella pneumoniae

High dose amoxicillinIg tds

Ampicillin

Mycoplasma pneumoniae

Amoxicillin-clavulanate2g bd

Ceftriaxone, Cefotaxime

Chlamydia pneumoniae

Ceftriaxone, cefuroxime, cefpodoxime

Ertapenem for some with risk factors for gram - other than Pseudomonas

Community acquired pneumonia:Macrolides

Addition of macrolide to beta-lactam therapy:

• Appears superior to respiratory fluoroquinolone monotherapy:

• Provides coverage for atypical pathogens

• Macrolides may modulate the host’s inflammatory response, even when used as monotherapy

Editorial commentary , CID 2008: (15 May)

Community Acquired Respiratory Tract Infections (CARTI)

• Bacterial rhinosinusitis• Acute exacerbations of chronic bronchitis (COPD)• Pneumonia

• Increased resistance of Strep pneumoniae (MIC > 2 mcg/ml = high level resistance) to:– Penicillins– Macrolides (previous use of long acting macrolides)– Fluoroquinolones

– Morbidity and mortality greater with PNRSP than PSSP (18.5% vs 12.2%)

– Level of penicillin resistance in S. Pneumoniae at present only precludes the use of penicillin in meningitis caused by these organisms in South Africa

Risk factors for Drug Resistant S. Pneumoniae (DRSP)

• Chronic comorbidity: heart, lung, liver, renal disease

• DM• Alcoholism• Malignancies• Asplenia• Immunosuppressant drugs• Use of antimicrobials within last 3 months (use dif.

class)

Severe CAP:combination therapy required

• Ps. Aeruginosa:Piperacillin – tazobactin + fluoroquinolone

• MRSA emerging as CAP pathogen:Add Vancomycin or Linezolid

• Alter empiric to pathogen-directed therapy once culture results known

• Switch from iv to oral once haemodynamically stable• Discharge as soon as clinically stable.

• Ertapenem acceptable alternative • Telithromycin not yet adequately assessed for CAP.

Urinary Tract Infections

Overview

• Types of UTIs• Diagnosis• Pathogens• Goals of treatment• Antimicrobials• Resistant patterns

UTI• Presence of micro-organisms in the urinary tract that cannot be

accounted for by contamination (> 10² /ml)• Range: asymptomatic bacteriuria to pyelonephritis with bacteraemia

or sepsis• Lower Tract Infections: frequency, dysuria, suprapubic pain,

haematuria– Cystitis– Urethritis– Prostatitis– Epididymitis

• Upper tract Infection: flank pain, systemic illness (vomiting, fever, etc)– Pyelonephritis

Types of UTI

UNCOMPLICATED• No structural or functional

abnormalities of urinary tract that interfere with normal flow of urine / voiding mechanisms

• Females of childbearing age who are otherwise healthy

• Lower urinary tract only

COMPLICATED• Predisposing lesion of the

urinary tract• Congenital abnormality• Renal stone• Indwelling catheter• Prostatic hypertrophy• Obstruction• Neurological deficit• Upper and lower urinary tract• Males and females

Bacteria enter the urinary tract.Factors determining development of infection:

1. Size of inoculum2. Virulence of micro-organism3. Natural host defence mechanisms

Aetiology:bowel flora of the host

UNCOMPLICATED UTI

• E-Coli (85%)• Staph. Saprophyticus (5-15%)

• Klebsiella (<1%)• Proteus (<1%)• Enterococcus (<1%)• Pseudomonas (<1%)

COMPLICATED UTI

• E-coli (50%)• Enterococci (esp nosocomial)• Pseudomonas• Klebsiella• Proteus• StaphylococciMore resistanceSometimes multiple organisms

Staph Aureus from bacteraemia, causing metastatic abscesses in kidneyCandida common in critically ill, chronic catheterisation

Notes on the flora:E-Coli

• Increasing resistance to antimicrobials• ? 30% resistant to amoxicillin, ampicillin and

cephalosporins• Oral beta lactams eliminated rapidly;

– unable to reach high renal tissue concentrations compared to others

– Less successful at eradicating uropathogens from vaginal and GIT reservoirs

• Increasing resistance to sulphonamides• Current or recent antibiotic exposure most

significant risk factor associated with E-Coli resistance

Notes on the flora:Enterococci

• Extensive use of third generation cephalosporins which are not active against enterococci

• Vancomycin resistant enterococci (VRE)– E. faecalis + S. faecium– Widespread– Patients after long term hospitalisation– Patients with underlying malignancies

Treatment of UTI

Desired Outcome:• Treat or prevent systemic consequences of infection• Eradicate invading organism• Prevent recurrence of infection

‘The ability to eradicate bacteria from the urine is related directly to the sensitivity of the micro-organism and the achievable concentration of the antimicrobial agent in the urine.’

Rx of Acute Uncomplicated UTI

Cost effective approach to management• Urinalysis• Initiation of empiric therapy • No culture

Short course antibiotics• Increased compliance• Good efficacy• Fewer side effects• Lower cost• Less potential for development of resistance

UTI antimicrobial options

Community acquired

1. Quinolones2. Fosfomycin3. Nitrofurantoin4. Co-amoxiclav5. Cephalosporins6. Co-trimoxazole

Severe or Hospital acquired

1. Aminoglycosides2. Piperacillin-tazobactam3. Imipenem-cilastin

Rx UTI: cystitisUncomplicated cystitis in non- pregnant women

• Fluoroquinolone (cipro-, levo-, norfloxacin)

• Ciprofloxacin 250mg stat

Asymptomatic bacteriuria

• Fluoroquinolone (cipro, levo, norfloxacin)

• Ciprofloxacin 250mg stat or• Ciprofloxacin 250mg bd for

3 days

Avoid in pregnancy

Rx UTI: Complicated cystitis

• Fluoroquinolone: Ciprofloxacin for 3 days

• Co-amoxiclav for 7 days• Nitrofurantoin for 7 days• 2nd generation cephalosporin: cephalexin,

cefuroxime for 7 days

Rx UTI: pyelonephritis

Uncomplicated pyelonephritis CultureOutpatient

14 day course of oral• Fluoroquinolone - ciprofloxacin

Rx UTI: pyelonephritis

Complicated pyelonephritis (Culture, admit. )14 days: start intravenous, switch to oral when afebrile• Fluoroquinolone• Extended spectrum penicillin + aminoglycoside

Hospital acquired, catheter, nursing home: Pseudomonas

• Antipseudomonas penicillin + aminoglycoside

UTITypes Bugs Drug

Uncomplicated cystitis in non-pregnant women

coliforms Ciprofloxacin one dose stat

Complicated cystitis coliforms Ciprofloxacin x 3/7Co-amoxiclav x 7/7Nitrofurantoin x 7/72nd G cephalosporin x 7/7

Uncomplicated pyelonephritis

coliforms Ciprofloxacin x 14/7

Complicated pyelonephritis

coliforms IV fluoroquinolones orAmpicillin + aminoglycoside

Hospital acquired Pseudomonas Piperacillin + aminoglycoside

UTI in pregnancy coliforms NitrofurantoinAvoid fluoroquinolones

Overall summary – outpatient treatment

Infection Bugs Ist line Alternatives

Pharyngitis/Tonsillitis

Viral 80%S. Pyogenes (GABHS)

Pen VK AmoxicillinClindamycin (allergy) orMacrolide(allergy)

SinusitisAcute otitis media

Strep. pneumoniaeH. Influenzae

Moraxella catarrhalis

Amoxicillin Co-amoxiclav if chronicErythromycin (allergy)Moxifloxacin (allergy)Doxycycline (Moraxella)

Pneumonia (CAP) Strep. pneumoniaeH. Influenzae

Atypicals: Legionella, Chlamydia, Mycoplasma

Macrolide

Doxycycline

Respiratory quinolone (Moxiflox) if risk factors

Add beta lactam to macrolide if risk factors

Cystitisuncomplicated

E-ColiOther coliforms

Ciprofloxacin stat(non-pregnant; uncomplicated)

Ciprofloxacin 3/7Co-amoxiclav 7/7Nitrofurantoin (pregnant)

The End