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