17/11/58

Methee Chayakulkeeree, MD, PhD

Associate Professor
Division of Infectious Diseases and Tropical Medicine
Department of Medicine, Faculty of Medicine Siriraj Hospital
Mahidol University

Topics
To prevent infection ( )
Medicial prophylaxis HIV
Surgical prophylaxis

To treat infection ( )
Common pitfalls in antimicrobial therapy Empirical treatment ( )


Specific treatment ( )

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Concepts
Each clinical syndrome can be caused by various pathogens
:
Each organism can cause various clinical syndromes
:
Empirical Specific

Diagnosis: antimicrobial antimicrobial

Clinical manifestations:
treatment treatment
Laboratory findings: PCR

Bed ridden: pneumonia, UTI, bed sore
Hospitalized: pneumonia, phlebitis, UTI, CRBSI
Febrile neutropenia: perineum infection, phlebitis

Urgent: Noturgent:
HIV: disseminated infection, opportunistic infections
Start empirical
Septic work up and close , ,
Septic work up
antibiotics
Start empirical observe
Cirrhosis: bacterial peritonitis, skin and soft tissue infection
antibiotics
: lymph nodes, skin sign
Wait
and
See
Unknown
organism
Known Organism
(No antibiotics)
(No

- Empirical antibiotic - Specific antibiotics
- Empirical antibiotic - Specific antibiotics

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Upper Respiratory Tract Infections Upper Respiratory Tract Infections

10
/ 90 ( 60)


10

No antibiotics for NON-bacterial infection!

12-72 1 2
3-4

3 4

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-



3-5 4-5 5-7 7-14

/ ?

Rhinovirus 20% Group A streptococci 15 30 %
Coronavirus 5% Group C streptococci
Adenovirus (type 3, 4, 7, 14, 21) Group G streptococci
Epstein-Barr virus: infectious Anaerobic bacteria
mononucleosis Neisseria gonorrhoea
Coxsakcievirus A (type 2, 4-6, 8, 10): Arcanobacterium haemolyticum
hand-foot-mouth Yersinia enterocolitica
Herpes simplex virus (type 1, 2) Corynebacterium diphheriae
Cytomegalovirus Treponema pallidum
Influenza (A,B,C)
Parainfluenza (type 1 4)

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Group A Streptococcal Pharyngitis Streptococcal Cervical Adenitis

GAS (Centor criteria)

3
1. ( >38C)
2. exudate/pustule /
3. (anterior cervical lymph nodes) /

(submandibular lymph nodes)

4.

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penicillin V GAS /
penicillins
amoxicillin penicillin V co-amoxiclav,
ampicillin+sulbactam, cephalosporins
penicillin roxithromycin fluoroquinolones ( levofloxacin
erythromycin syrup moxifloxacin)
10 rheumatic fever

Community-Acquired Pneumonia
( )
/ Inhalation, aspiration and
hematogenous spread are
/ ( serratiopeptidase the 3 main mechanisms Inhalation
enzyme) by which bacteria reaches
the lungs
Aspiration
/
( benzathine penicillin G )
1.2 mU for BW 27 kgs Hematogenous
0.6 mU for BW < 27 kgs
lincomycin, ceftriaxone

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Community-Acquired Pneumonia Community-Acquired Pneumonia

Risk Factors in Patients
Requiring Hospitalization
older, unemployed
common cold in the previous year
asthma, COPD; steroid or
bronchodilator use
Chronic disease
amount of smoking
Risk Factors for Mortality
age
bacteremia (for S. pneumoniae)
extent of radiographic changes
degree of immunosuppression
amount of alcohol
Microbiology
S. pneumoniae: 20-60% Legionella spp. 2-8%
H. influenzae: 3-10% S. aureus: 3-5%
Chlamydia pneumoniae: 4-6% Gram negative bacilli: 3-5%
Mycoplasma pneumonaie: 1-6% Viruses: 2-13%
40-60% - NO CAUSE IDENTIFIED
2-5% - TWO OR MORE CAUSES

Signs and Symptoms Chest Radiograph

Fever or hypothermia May show hyper-expansion, atelectasis or infiltrates
Cough with or without sputum, hemoptysis
Pleuritic chest pain
Myalgia, malaise, fatigue
GI symptoms
Dyspnea
Rales, rhonchi, wheezing
Egophony, bronchial breath sounds
Dullness to percussion
Atypical Sxs in older patients Normal Pneumonia

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Infiltrate Patterns Outpatient Management in Previously Healthy Patients

Organisms: S. pneumoniae, Mycoplasma, viral,
Pattern Possible Diagnosis
Chlamydia pneumoniae, H. influenzae
Lobar S. pneumoniae, K. pneumoniae, H. Recommended abx:
influenzae, Gram-negative bacteria
Patchy Atypicals, viral, Legionella Advanced generation macrolide (azithro or clarithro) or
doxycycline
Interstitial Viral, PCP, Legionella
If abx within past 3 months:
Cavitary Anaerobes, K. pneumoniae, S. aureus, Respiratory quinolone (moxi-, levo-, gemi-), OR
fungi, TB
Large effusion S. aureus, anaerobes, K. pneumoniae Advanced macrolide + amoxicillin, OR
Advanced macrolide + amoxicillin-clavulanate

Outpatient Management in Patients with comorbidities Inpatient Management: Medical Ward

Comorbidities: cardiopulmonary diseases or Organisms: all of the above plus polymicrobial infections
immunocompromised state (+/- anaerobes), Legionella
Recommended Abx: Recommended Parenteral Abx:
Respiratory quinolone, OR advanced macrolide Respiratory fluoroquinolone, OR
Recent Abx: Advanced macrolide plus a beta-lactam
Respiratory quinolone OR Recent Abx:
Advanced macrolide + beta-lactam As above. Regimen selected will depend on nature of
recent antibiotic therapy.

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Inpatient Management: Severe/ICU Switch to Oral Therapy

No risk for Pseudomonas Four criteria:
IV beta-lactam plus either
Improvement in cough and dyspnea
IV macrolide, OR IV fluoroquinolone
Afebrile on two occasions 8 h apart
Risk for Pseudomonas
Double therapy: selected IV antipseudomonal beta-lactam (cefepine, WBC decreasing
imipenem, meropenem, piperacillin/tazobactam), plus Functioning GI tract with adequate oral intake
IV antipseudomonal quinolone
If overall clinical picture is otherwise favorable, can can
Triple therapy: selected IV antipseudomonal beta-lactam plus
IV aminoglycoside plus either IV macrolide, OR IV antipseudomonal switch to oral therapy while still febrile.
quinolone

Duration of Therapy Urinary tract infection (UTI)

Minimum of 5 days
Afebrile for at least 48 to 72 h Acute uncomplicated UTI

No > 1 CAP-associated sign of clinical instability Acute complicated UTI

Longer duration of therapy
If initial therapy was not active against the identified pathogen or Catheter associated UTI

complicated by extra pulmonary infection

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Case 1 Case 1
A 24-year-old woman presented with lower
Which one is the most appropriate
abdominal pain, dysuria, and voiding frequency
antimicrobial treatment ?
for 3 days.

A. Cotrimoxazole(800/160 mg) 1 tab twice daily x 3 d

PE: no fever
B. Ciprofloxacin(250 mg) 1 tab twice daily x 3 d
Abdomen: soft, no tenderness, no guarding,
CVA- no tenderness C. Nitrofurantoin(100 mg) 1 tab twice daily x 5 d
D. Fosfomycin(3 g) 1 sachet single dose
UA: WBC 30-50/hpf, RBC 2-3/hpf, epith 0-1/hpf E. Cefdinir(100 mg) 1 tab twice daily x 5 d

Acute uncomplicated UTI Diagnosis

Cystitis vs Urethritis or cervicitis

Symptoms and signs
Pyelonephritis
Healthy, non pregnant
premenopausal woman
Pyuria and/or hematuria
UA
Leucocyte esterase, Nitrite

Acute cystitis
Acute pyelonephritis Pyelonephritis
Urine C/S Recurrence
Failure
MDR bacteria

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Epidemiology Guideline
S.saprophyticus

Enterococcus
spp.
Acute uncomplicated cystitis
E.coli
1st line antibiotics
K.pneumoniae

Other
Nitrofurantoin Co-trimoxazole Fosfomycin
100 mg bid x 5 d 800/160 mg bid x 3 d 3 g single dose

NARST
% resistance
Ampicillin 75-80
Co-trimoxazole 60-70
Ciprofloxacin 40-50
Ceftriaxone 3-15

Guideline Guideline
Acute uncomplicated cystitis Acute uncomplicated pyelonephritis
Alternative antibiotics
Severe illness
Unstable hemodynamics
Fluoroquinolones lactams Intolerance to oral ATB
Unreliable adherence
Ciprofloxacin Amoxicillin/clavulanate
250 mg bid x 3 d Cefdinir
Levofloxacin
250-500 mg od x 3 d Admit
OPD management
Not used as 1st line if the prevalence of FQ resistance > 10%

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Oral ATB Rx for acute uncomplicated

Guideline pyelonephritis

Acute uncomplicated pyelonephritis

Type of oral ATB Dosing regimen
OPD management
Prevalence: FQ resistance > 10% Quinolones
Previous co-trimoxazole or lactams Ciprofloxacin 500 mg bid x 7 d
Levofloxacin 750 mg od x 5 d
Yes No Co-trimoxazole 800/160 mg bid x 14 d

Empirical IV ATB Empirical oral ATB lactams

Ceftriaxone or AMGs Cefixime 400 mg od x 10 d
Cefditoren pivoxil 400 mg od x 10 d
Optimize appropriate oral ATB by U/C

Case 2 Case 2
A 65-year-old woman with poorly controlled T2DM Which one is the most appropriate empirical
complained of fever, shaking chill, and antimicrobial treatment ?
flank pain for 4 days. She took 4 doses of ciprofloxacin, but
symptoms has been ongoing.
A. Ciprofloxacin IV
B. Gentamicin IV
PE: T 38.7 c, BP 80/60, P 124/min
C. Ceftazidime IV
CVA- tenderness
D. Ceftriaxone IV
UA: WBC 30-50/hpf, RBC 2-3/hpf, epith 0-1/hpf E. Imipenem IV

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Acute complicated UTI Epidemiology

Stone, tumor,
MDR
obstruction,
organism ESBL producing E. coli and K. pneumoniae 10-30 %
catheter
ESBL producing P. mirabilis 10 %
Autonomic Severe
dysfunction complication
MDR P. aeruginosa 50-60 %
MDR A. baumannii 70%

Pregnancy,
male, elderly Cost

Comorbidity Mortality

Diagnosis Management
Lower or upper UTI
Symptoms and signs
Non specific illness
Initial assessment
Sepsis/septic shock Not severely ill Severe infection
UA Complication Lower UTI Immunocompromised
Complicated infection
Urine C/S Local data MDR organism ?

Empirical ATB treatment

Blood C/S Sepsis
Clinical evaluation and ATB modification at 48-72 h
Radiological study Obstruction
Complication Further evaluation and treatment

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Empirical ATB Rx guideline Monitoring

Acute complicated upper UTI Clinical evaluation at 48-72 h
Not severely ill Severely ill
No MDR risk Immunocompromised
MDR risk Improved Not improved

Quinolones Quinolones (high dose)

Cephalosporins with anti-PA
ATB modification Radiological evaluation
3rd cephalosporins
+/- surgical intervention
Aminoglycosides (AMGs) Anti-PA lactams
ATB modification
Carbapenems (MDRO)
* Initially high appropriate dose * +/- Vancomycin
+/- AMGs Duration of ATB 7-14 days

Case 3 Case 3
Urine C/S :
A 68-year-old man was suffered from ICH, and admitted to
the hospital for 4 week.
- retained urethral catheter and NG tube feeding
Enterobacter cloacae > 103-104 cfu/mL
- intermittent fever Enterococcus faecalis > 104 cfu/mL
- ongoing iv ceftriaxone for 10 days yeasts > 103 cfu/mL
PE: stable V/S; Others- WNL
UA: WBC 30-50/hpf, RBC 0-1/hpf, epith 0-1/hpf
How can we manage this patient ?

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CA-UTI: Definition Diagnosis

Symptoms and signs Non specific

Retention
48 h UA Non specific
or
Removal Diagnostic
Quantitative urine C/S 103 cfu/mL
48 h 1-2 microorganisms

* Exclude other etiologies of infection *

Guideline Guideline(cont)
Fever in patient with retained urine catheter
Symptoms/signs, pyuria + without other causes

CA-UTI ?
Empirical ATB by local epidemiological data

Exclude other causes*** Urine C/S

Appropriate ATB modification

Change catheter if the catheter Duration: 7-14 days
was retained > 2 week (evidence C)

Re-evaluate indication of urine catheterization

UA, Urine C/S Use alternative urinary drainage

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Surgical Prophylaxis Antimicrobial Prophylaxis

General concepts
Common pathogens: skin flora (S. aureus and coagulase-negative
staphylococci)
clean-contaminated procedures: gram-negative rods and
enterococci in addition to skin flora.
FDA-approved agents: cefazolin, cefuroxime, cefoxitin, cefotetan,
ertapenem, and vancomycin
For most procedures, cefazolin is the drug of choice because it is the
most widely studied antimicrobial agent, with proven efficacy.
Start within 1 hour before incision and NO more than 24 hours after
operation

Antimicrobial Prophylaxis Antimicrobial Prophylaxis

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Antimicrobial Prophylaxis

Common Pitfalls in Antimicrobial Therapy

Practical Point and Pitfall 1 Sputum Examination

colonization
- CXR
-

- colonization


- asymptomatic bacteriuria

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Sputum Examination (Gram stain) Practical Point and Pitfall 2

Asymptomatic Bacteriuria ( )






(neutropenia)

Presence of numerous mixed gram positive cocci,

gram negative bacilli, and gram positive bacilli

Practical Point and Pitfall 3

Inadequate spectrum of ATB inactivation (ATB
ATBs antagonism or interaction)
Inadequate ATB blood and Superinfection
tissue levels
(prolonged fevers) ATB-unresponsive infectious
Undrained abscess
Non-infectious medical disorders diseases; viral infections
Foreign body-related infection
(e.g., SLE, malignancies leukemia) Antibiotic resistance
Organ barrier: CSF, eye, bone,
vegetation, prostate Non-infectious cause
Drug fever ( )
Organ hypoperfusion
Complication

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Practical Point and Pitfall 4 Streptococcus pneumoniae meningitis
Penicillin MIC < 0.06 g/mL
Ceftriaxone High dose (4 gm/day)
Case Scenario Clindamycin
Poorly cross
40 Vancomycin blood brain barrier
2 Piperacillin/tazobactam
T = 38.5C, conscious, stiffness of neck Meropenem OK but too broad
Streptococcus pneumoniae
Lumbar puncture Imipenem Not approved for CNS infection
Opening pressure/close pressure: 25/22 cm H2O Azithromycin Poorly cross BBB
CSF: WBC 1,000/mm3, 95% PMN, protein 150 mg/dL, CSF/Serum glucose 20/100 Levofloxacin Little clinical evidence
mg/dL

Tissue Penetration of Antibiotics Bactericidal and Bacteriostatic

Special barrier or abscesses Bactericidal agents cause Bacteriostatic agents
death and disruption of the inhibit bacterial replication
Ocular, fluid, CSF, abscess cavity, prostate, bone
bacteria without killing the organis
o -lactams o Sulfonamide
o Fluoroquinolones o Tetracyclines

Moxifloxacin UTI o Aminoglycosides o Macrolides

o Colistin Clindamycin
Aminoglycosides:
o

: low-oxygen, low pH, abscesses ( drain - No ATB is bactericidal to Entorococcus spp.

abscess )
(only penicillin+gentamicin or streptomicin)
- Bactericidal agents are in the serious infections to achieve rapid
cure such as endocarditis and meningitis

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Practical Point and Pitfall 5 Combination Therapy: Synergy

Use combination therapy only neccessary -lactams and aminoglycosides exhibits
Monotherapy; preferred over combination synergism for treatment of endocarditis
therapy -> reduces the risk of caused by;
Drug interactions Enterococcus spp.
Medication errors
Viridans streptococci
Missed doses and side effects
Usually less expensive than combination therapy Staphylococcus aureus

Combination Therapy Penicllin and clindamycin: clinical synergism for

Drug synergy
treatment of S. pyogenes infection
Extended spectrum
Prevent resistance

Practical Point and Pitfall 6 Practical Point and Pitfall 7

Gram stain (anaerobes )
Misinterpretation of antimicrobial susceptibility testing
A 70 Years Old Female
Post intra-abdominal surgery and prolonged hospital stay S. aureus clindamycin
Fever for 2 days with surgical wound infection erythromycin resistance
BP= 90/60, P= 120/min, R = 32/min
Retained NG tube, bowel ileus D test
Inducible MLSB Phenotype
Pus gram stain: numerous Gram-negative rod, few Gram-positive rod and cocci in (Inducible resistance to clindamycin)
group and chain
Clindamycin
Pus culture grew gram-negative bacilli E. coli
Erythromycin

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Practical Point and Pitfall 8 78 COPD

3 Sputum culture :
Advantages Disadvantages Haemophilus influenzae,
CXR: multilobar infiltraion
Intubation and admitted beta-lactamase positive

IV IV ceftriaxone + oral
IV shock,

NPO clarithromycin

Beta-Lactam Resistance in Haemophilus influenzae

Approximately 50% of Haemophilus influenzae and almost all of IV
Moraxella catarrhalis produce betalatamases admit

Batalactam-batalactamase inhibitor (BLBI) such as
discharge
amoxicillin/clavulanate should be used

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Well absorbed drug:

Fluoroquinolones (except norfloxacin)
Metronidazole
Tetracycline, minocycline, doxycycline
Linezolid,
Trimethoprim-sulfamethoxazole
interaction
Oral Administration

Better bioavailability Amoxicillin > PenV > Ampicillin
Dicloxacillin is relatively better absorbed than cloxacillin (250 dicloxacillin is
NOT equal to 500 mg cloxacillin)
Oral cephalosporin is absorbed better than penicillin group

Bioavailability of oral antibiotics How can we switch from IV to oral?

> 95% 90-95% 80-89% < 80%
Cephalexin Clindamycin Amoxicillin Amoxycillin/ Use antibiotics with similar spectrum
Clavulanic acid
( )
Cotrimoxazole Doxycycline Ampicillin/ Clarithromycin
Sulbactam Sequential therapy is the best option ( )
Levofloxacin Ofloxacin Ciprofloxacin Dicloxacillin Step down therapy is not recommended unless necessary
Linezolid Tetracycline Cefditoren pivoxil
Metronidazole Cefixime
Ceftibuten Use antibiotics with good oral bioavailability (>50%)
Cefuroxime axetil
Cefpodoxime proxitil Consider PK/PD of both IV/oral regimens

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switch Practical Point and Pitfall 9

Cannot use oral route (risk of aspiration, need for complete bowel rest, Interaction with food and other drugs
gastrointestinal obstruction, preoperative/postoperative fast)
50 chronic kidney diseases, iron deficiency anemia
Unreliable response to oral medication (severe nausea/vomiting, continuous furosemide, FeSO4, CaCO3, alum milk, nifedipine, simvastatin, folic acid
nasogastric suction, malabsorption syndrome, motility disorder of the liver abscess
gastrointestinal tract, unresponsive to previous oral therapy, short bowel
Hemoculture and pus culture: Klebsiella pneumoniae
syndrome)
Treatment: ceftriaxone 14 days ciprofloxacin

Infection does not permit conversion (high-risk neutropenia, meningitis,
endocarditis) ???

Effect of Food on Absorption Common Drug Interactions

Co-administration of rifampicin and itraconazole is ABSOLUTE
Drug interactions
contraindicated
- Multivalent cations (2+, 3+) such as aluminum, Fe, magnesium, and
Rifampicin and protease inhibitor is contraindicated
calcium in antacids

Itraconazole tablet/capsule (30-40 %)

60-70 %
- Decrease the intestinal absorption of fluoroquinolones and
Itraconazole solution 1
tetracyclines
Itraconazole and protease inhibitor, NNRTI (nevirapine, efavirenz) exhibits
significant interaction!
2

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Thank You

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