Download Pneumonia-What is the infection?

Bugs and Drugs
Nawal AL Kaabi, MBBS, FAAP, FRCPC
Pediatric Infectious disease consultant
Deputy CMO
Adjunct Faculty Cleveland clinic
SKMC, Managed by Cleveland Clinic
SEHA
Objectives
 To learn an approach to antibiotic use using
illustrative clinical scenarios:
 Skin and soft tissue infections
 Cellulitis
 Periorbital/Orbital cellulitis
 Necrotizing fasciitis
 Sepsis
 Meningitis
 Urinary Tract Infections/Pyelonephritis
 Pneumonia
Approach to Antibiotic Use
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Approach to Antibiotic Use
 What is the infection?
 What are the most common organisms?
 What are their resistance patterns?
 Where is the infection?
 Where does the drug need to get to?
 Who is the host?




Age
status of immune system
allergies
underlying illness-eg, hepatic/renal dysfunction
Approach-2
 How do I diagnose the infection?
 Which Antibiotics should I use?
 Parenteral (intravenous) vs. oral
 side effects
 taste
 cost
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
1. Natural Penicillin:
 Penicillin G, Penicillin V
 Most active against :
1. non-B-lactamase producing gram positive bacteria-
Streptococcus pyogenes (Group A Streptococcus),
susceptible Streptococcus pneumoniae.
Streptococcus agalactiae (Group B Streptococcus)
2. Anaerobespeptostreptococcus, Corynebacterium diphtheriae, and Colstridium perfringens
Natural Penicillin
Most active against
3. Susceptible Neisseria meningitidis.
4. Treponema pallidum (Syphilis)
Not active against
 Staphylococcus
 Most Gram negatives
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
2. Penicillinase-resistant Penicillins
 Methicillin, Cloxacillin, Oxacillin.
 Drug of choice for S.aureus
 unless MRSA
 If S. aureus is resistant to cloxacillin it is resistant to all
-lactams
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
3. Aminopenicillins
 Ampicillin and Amoxicillin
 Possess the same spectrum as penicillin G plus
they are more active against non-B lactamase
producing gram negative cocci and some
Enterobacteriaceae like Salmonella
 Listeria monocytogenes (ampicillin)
 First line for acute otitis media ( high dose Amoxil)
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
4. Extended-spectrum ureidopenicillins and Carboxyand indanyl penicillins
 Piperacillin and Ticarcillin
 Increased gram negative coverage to include
Pseudomonas
 Bacteroides, other anaerobes
 Most gram positive, including Enterococci
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
First Generation Cephalosporins :
 Parenteral: cefazolin
 Oral: cephalexin
 Active against gram positive cocci and have moderate
activity against Moraxella catarrhalis, E.coli and some K.
pneumoniae.
 Appropriate for S.aureus and non-enterococcal
streptococcal infections
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
Second Generation Cephalosporins
 Parenteral: Cefuroxime
 Oral: Cefaclor, Cefuroxime axetil,
 Increased activity against H.influenzae,
M.catarrhalis,
 Enterobacteriaceae: e.g Enterobacter, Klebsiella,
Salmonella, Serratia, Shigella
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
Third Generation Cephalosporins
 Parenteral: Cefotaxime, Ceftriaxone and Ceftazidime
 Oral: Cefixime
 Active against facultative gram negative bacilli.
 They have potent antimicrobial activity against
S.pneumoniae, S.pyogenes, and other streptococci, and
with the exception of ceftazidime, have some activity
against S.aureus
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
Third Generation Cephalosporins
 Also active against E.coli, Klebsiella
 Cefotaxime and ceftriaxone very effective
therapy for meningitis caused by S.pneumoniae,
H.influenzae, Neisseria meningitidis,
 Drug of choice for empiric therapy for
meningitis
 Ceftazidime is the agent of choice for meningitis
due to P.aeruginosa
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
Aminoglycosides
 Aerobic gram-negative organisms
 No antianaerobic activity
 Enterococci: only gram positive organism for
which aminoglycosides are considered the drug
of choice (with either penicillin/ampicillin or
vancomycin)
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
Clindamycin
 gram positive cocci and anaerobes
 Active against many staphylococci (including
penicillinase producers but not all MRSA)
 anaerobic lung abscess
 invasive GAS ( with penicillin)
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
Macrolides
 Clarithromycin and azithromycin extend
erythromycin coverage to include more respiratory
pathogens (esp. H. Influenzae)
 not recommended as first line therapy for otitis media
or respiratory infections
Vancomycin
 Essentially all gram positive and only gram positive
organisms
Approach to Antibiotic Use
Antibacterial Spectrum of Antibiotic
CARBAPENEMS
 CARBAPENEMS are a class of beta-lactum,
broad spectrum antibiotics which act by inhibiting the cell wall synthesis and
are known to be most effective against gram negative infections.
 Carbapenems, often in combination with other agents, remain a mainstay
of therapy in patients with serious hospital-acquired infection.
 Carbapenems can be grouped as (2),
 Group 1 includes broad-spectrum Carbapenems, with limited activity
against non-fermentative Gram-negative bacilli, particularly suitable for
community acquired infections (e.g. ertapenem).
 Group 2 includes broad-spectrum Carbapenems, with activity against nonfermentative Gram-negative bacilli that are particularly suitable for
nosocomial infections (e.g. imipenem and meropenem)
Case #1
 3 year old boy at family farm for the weekend
 Sustains many mosquito bites which he has been scratching
 Develops erythema around facial bites which is now
spreading
 Has a low grade fever
 Otherwise a healthy boy with no known drug allergies
Case #1
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
What is the infection?
 Cellulitis
 What are the most common organisms?
 What are their resistance patterns?
Cellulitis-What is the infection?
 Common organisms:
 Staphylococcus aureus
 Group A Streptococcus (GAS)
 Resistance patterns:
 Increasing antibiotic resistance of Staphylococcus aureus
 No known cases of penicillin resistance for GAS
Case #1
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Cellulitis-Where is the infection?
 Skin +/- blood
Cellulitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Cellulitis- Who is the host?
 Age
 Status of immune system
 Allergies
 Underlying illness-eg, hepatic or renal dysfunction
Cellulitis- Who is the host?
 Age
 Newborn– Include Group B Streptococcus in the differential
diagnosis
 Status of the immune system
 In immunocompromised patients, consider Pseudomonas,
Cryptococcus, in the differential diagnosis
Cellulitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Cellulitis- How to diagnose?
 History can be very helpful- examples:
 Cellulitis following animal/human bites?
 recent dental work?
 Physical exam
 Lab
 Complete blood count/differential, blood c/s may be helpful
Cellulitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Cellulitis-Which Abx?
Parenteral vs. Oral?
Cellulitis-Which Abx?
 Parenteral therapy generally used in the following situations:
 Newborn babies
 Severe +/- rapidly progressing cellulitis
 lymphangitis/adenitis
 First line parenteral agent:
 Cefazolin/Fluclox/clindamycin
 First line oral agents:
 cephalexin
 Clavulin (amoxicillin + clavulinic acid)
 Clindamycin
IDSA Guidelines for CA-MRSA
Endorsed by the AAP
January 2011
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
CA-MRSA:
Treatment for Skin / Skin Structure
Infections (SSTI)
 Hospitalized children with complicated SSTI:
 Vancomycin
 Clindamycin is an option if the patient is stable,
without ongoing bacteremia or intravascular infection,
and if the clindamycin resistance rate is low (eg,10%);
allows transition to oral therapy
 Linezolid is an alternative
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
CA-MRSA:
Treatment for Skin / Skin Structure Infections
(SSTI)
 I&D for MRSA abscess is curative
 Oral antibiotics for Cellulitis:
 Clindamycin (if local strains susceptible) Staph + Strep
[tastes bad]
 TMP-SMX (Septra/Bactrim) Staph + ?Strep
 Doxycycline [bacteriostatic, for children older than 7
years]
 Linezolid (Zyvox) Staph + Strep [expensive! Marrow
toxicity for courses beyond 10 days]
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
Necrotizing Fasciitis
 Rapidly progressive infection of fascia which may extend
into muscle
 Patients generally look toxic
 Infected area exquisitely tender which is often out of
keeping with appearance
 A potential complication of any cutaneous cellulitis
 An association also exists between varicella, NSAID use and the
development of necrotizing fasciitis
 Therefore, NSAIDs should not be used in patients with varicella
Necrotizing Fasciitis
 Most often caused by GAS now
 can also be caused by Staphylococcus aureus
 consider gram negative organisms and anaerobes in differential
diagnosis as well (especially if gas producing)
Necrotizing Fasciitis
 Treatment:
 Empiric Therapy:
 cefazolin + clindamycin
 GAS known/highly likely:
 penicillin + clindamycin
 Surgical debridement (do not delay!)
 MRI may be helpful if diagnosis is in doubt
 Intravenous immunoglobulin
Periorbital, Orbital Cellulitis
 Periorbital (preseptal) Cellulitis
 predisposing factors include trauma (including bites),
impetigo, URI
 Usual causative organisms
 GAS
 Staphylococcus aureus
 Patients usually afebrile, non-toxic appearing
 Rx: cefazolin or cefuroxime +/- clindamycin
Important to distinguish periorbital
from orbital cellulitis!
(Can be difficult to tell the difference)
Orbital Cellulitis
 Infection of the orbit (post-septal)
 Pathogenesis different than in periorbital infection
 Systemic signs often present
 Local signs may include:




proptosis
impairment and pain with extraocular movements
loss of visual acuity
chemosis
 Possibility of extension into CSF!
ethmoid
orbit
Lamina papyracea
Orbital Cellulitis
 Usual etiologic organisms include:
 Staphylococcus aureus
 GAS
 “Sinus bugs”
 Streptococcus pneumoniae
 Haemophilus influenzae (non-typeable)
 Moraxella catarrhalis
 +/- Anaerobes
Orbital Cellulitis Treatment
 If concerned re CNS involvement or if neonate then
empiric therapy should include:
 Cefotaxime or Ceftriaxone
 Metronidazole
 Vancomycin
Case #2
 3 wk bb with fever, decreased feeding
 Otherwise, a healthy baby, normal pregnancy, labour and
delivery
 Physical exam reveals a lethargic, mottled baby with a
fever (39.5 rectal), and no focus of infection
What tests would you order?
Approach
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
What is the infection?
 Presumed sepsis +/- meningitis
 Common organisms- age dependant
 Resistance patterns-IMPORTANT
Sepsis/meningitis-What is the
infection?
 Common organisms:
 Newborn:
 Group B streptococcus
 Listeria
 Gram negative bacilli (eg, Escherichia coli)
 include Enterococcus, S. aureus for sepsis (not meningitis)
 >3 mos:
 Streptococcus pneumonia
 Neisseria meningitidis
 Haemophilus influenzae type B (rare since universal vaccination)
 1-3 mos: overlap
Sepsis/Meningitis-What is the
Infection?
 Resistance patterns
 Streptococcus pneumoniae
 increasing resistance to B-lactam antibiotics
 rates vary geographically
 due to altered penicillin binding proteins on cell
wall
Sepsis/Meningitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Sepsis, Meningitis-Where is the
Infection?
 Blood
 CSF
 Blood brain barrier more difficult to penetrate with age
 Some antibiotics penetrate CSF better than others
 May need higher doses
Sepsis, Meningitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Sepsis, Meningitis-Who is the host?
 Age dependent: as mentioned
 Underlying conditions can influence etiology-examples:
 Sickle cell disease at higher risk for encapsulated
bacteria (especially Salmonella sepsis)
 Central Venous catheters at risk for coagulase negative
Staphylococcus and gram negative bacilli
 VP shunt at risk of coagulase negative Staphylococcus
meningitis
Sepsis, Meningitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Sepsis, Meningitis-How to
diagnose?
 History
 variable presentation in neonates
 Physical exam
 Lab
 CBC diff, gm stain, blood C/S, other
 CSF cell count/diff, glucose, protein, gm stain, C/S
 Urinalysis, urine C/S
Sepsis, Meningitis
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which antibiotics?
Sepsis, Meningitis-Which
Antibiotics?
 For straightforward cases:
 <4 weeks: ampicillin/gentamicin
 alternative: amp/cefotaxime
 4-6 weeks: amp/cefotaxime
 >6 weeks: vancomycin/cefotaxime
 Remember meningitic doses!
Meningitis
 NEVER delay antibiotics if meningitis is suspected even
if it means LP is done after Abx started!
Case #3
 5 year old girl with 2 days fever, dysuria, left sided flank
pain, poor oral intake
 otherwise, past medical history unremarkable
 u/a: >50 WBCs, +nitrite, 2+ bacteria
 gram stain:
Pyelonephritis/Urinary Tract
Infection
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Pyelo/UTI
 Usual Organisms:
 Enterobacteriaceae (E. coli-70-90%, Klebsiella,
Proteus spp)
 Less commonly: Enterococcus, Pseudomonas
 Newborns: include GBS
 Adolescent females: include Staphylococcus saprophyticus
 Resistance Patterns
 Increasing resistance of enterobacteriaceae
 ESBL
Pyelo/UTI- Treatment
 Empiric parenteral therapy:
 ??ampicillin + gentamicin if uncomplicated
 Ampicillin should be included if enterococcal UTI is suspected.
 Third- or fourth-generation cephalosporins (eg, cefotaxime,
ceftriaxone, cefepime) and aminoglycosides (eg, Amikacin or
gentamicin) are appropriate first-line parenteral agents for
empiric treatment of UTI in children
 First line oral therapy:
 Trimethoprim/sulfamethoxazole (septra)
 Follow-up important
 remember imaging, VCUG
http://www.uptodate.com/contents/urinary-tract-infections-in-infants-and-children-older-than-one-month-acute-managementimaging-andprognosis?source=machineLearning&search=uti+children&selectedTitle=1%7E150&sectionRank=1&anchor=H5#H5
Pyelo/UTI- Treatment
 Recent antibiotic exposure — treatment or prophylaxis
 Recurrent UTI — Review of the antimicrobial susceptibilities
of the most recent urinary pathogens can be helpful in
choosing empiric therapy for children with recurrent UTI.
 First line oral therapy:
 Trimethoprim/sulfamethoxazole (septra)
 Amoxicillin-clavulanate
 Third-generation cephalosporin (eg, cefixime, cefdinir,
ceftibuten)
 Follow-up important
 remember imaging, VCUG
http://www.uptodate.com/contents/urinary-tract-infections-in-infants-and-children-older-than-one-month-acute-managementimaging-andprognosis?source=machineLearning&search=uti+children&selectedTitle=1%7E150&sectionRank=1&anchor=H5#H5
Pyelo/UTI- Treatment
ESBL
Parenteral therapy:
 Piperacillin-tazobactam is the 1st line if ESBL is sensitive
 Ertapenem. 2nd choice
 Meropenem or imipenem
 quinolones
 aminoglycosides
 Cefepime
Case #4
 5 year old girl with 6 days coryza, cough and escalating
fever
 Poor oral intake and vomiting
 Looks unwell on exam, in mild resp distress, temp 39 po,
HR 120, RR 25, decreased a/e RUL
 CXR:
Approach
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Pneumonia-What is the infection?
 Common organisms
 Newborn




GBS
Listeria
Gram negative bacilli
Chlamydia trachomatis
 Past newborn period:
 most common is viral (always consider first in winter)
 Bacterial……
Pneumonia-What is the infection?
 Bacterial causes of pneumonia past the newborn period:






Streptococcus pneumoniae
GAS
Staphylococcus aureus
Hemophilus influenzae
“atypicals” (eg, Mycoplasma pneumoniae)
Anaerobes
Pneumonia-What is the infection?
 Resistance patterns
 Increasing resistance of Streptococcus pneumoniae
to B-lactam antibiotics
 Due to altered penicillin binding proteins on cell
wall
 Resistance can be overcome by using high dose Blactam antibiotics (for infections outside of the CSF)
Approach
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Pneumonia-Where is the infection?
 Lungs +/- blood
 blood culture positive in only 30%
Approach
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Pneumonia-Who is the host?
 Age
 Underlying health status
 In immunocompromised patients (eg, those infected with
HIV), consider unusual pathogens including Pneumocystis
carinii, fungi, Cytomegalovirus
Pneumonia-Who is the host?
 Underlying conditions (cont’d)
 In patients with underlying neurological disease, consider
aspiration pneumonia
 In patients with nosocomial pneumonia, causative pathogens
often different
Approach
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Pneumonia-How to diagnose?
 History
 rapidity of onset, season can help
 Physical examination
 Labs
 CBCdiff sometimes unreliable
 Blood culture
 mycoplasma IgM may be helpful if index of
suspicion is present
 +/- sputum gm stain, culture (children often do not
expectorate though)
Pneumonia-What is the infection?
 CXR--sometimes not helpful in distinguishing bacterial
from viral etiology
 lobar: suggests typical bacteria
 pneumatocele: suggest Staphylococcus aureus
 effusion/abscesses: usually bacterial Streptococcus pneumoniae,
GAS, Staphylococcus aureus
 diffuse: suggests viruses, atypical bacteria, PCP, MERS-CoV,
NON-INFECTIOUS etc…
Approach
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Pneumonia--Which Abx?
 Indications for parenteral therapy:





Newborns with pneumonia
Toxic appearing patients
Those requiring oxygen
Vomiting, can’t tolerate oral therapy
Complications of pneumonia (abscess, empyema,
effusion)
 Parenteral therapy:
 Viral: no Rx, unless bacterial superinfection
suspected
Pneumonia-Which Abx?
CA-MRSA:
Community-Acquired Pneumonia (CAP)
 For children hospitalized with severe CAP empiric therapy for
MRSA is recommended (pending sputum and/or blood culture
results):
 Those requiring an intensive care unit (ICU) admission, OR
 Necrotizing or cavitary infiltrates, OR
 Empyema
 Vancomycin recommended for children
 If the patient is stable without ongoing bacteremia
or intravascular infection, clindamycin can be used
as empirical therapy if the clindamycin resistance rate is low
(eg, 10%)
 Linezolid is an alternative [watch for more data on this issue]
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases
Society of America for the treatment of methicillin-resistant Staphylococcus aureus
infections in adults and children. Clin Infect Dis. 2011;52:1-38.
CA-MRSA:
Vancomycin Dosing for Children
 Vancomycin 15 mg/kg/dose every 6 h (60 mg/kg/day) is
recommended for serious or invasive disease (data are
limited to guide vancomycin dosing in children).
 Trough concentrations of 15–20 mcg/mL should be
considered in those with serious infections, such as
bacteremia, infective endocarditis, osteomyelitis,
meningitis, pneumonia, and severe SSTI (eg, necrotizing
fasciitis)
Lui C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of
methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
Pneumonia-Which Abx?
 Parenteral Therapy
 Community acquired
bacterial pneumonia:
 newborn: ampicillin
+ gentamicin
 Older child:
Ampicillin
 Atypical bacteria:
erythromycin,
azithromycin
 Oral therapy:
 Amoxicillin
 Amox-Clav
 macrolide (especially if
atypical pneumonia
suspected)
Practice Case
 10 year old girl with mild cough x 8 days ,low
grade fever, myalgias
 6 year old sibling ill with similar symptoms
 Physical exam reveals that she is in mild
respiratory distress with an oxygen saturation
of 94% on room air, bullous myringitis,
moderate a/e bilat, but no wheezes/crackles
 WBC is normal
 CXR:
Practice Case
 What is the infection?
 Where is the infection?
 Who is the host?
 How to diagnose?
 Which Abx?
Take Home Message
How Can Resistance to Antimicrobials be minimized?
1. Limiting exposure to any antibiotic
2. Proper Antibiotics
3. Limiting the spectrum of activity of antimicrobials
4. Using the proper dosage of antimicrobials
5. Shortest effective duration
 2000 B.C. – Here, eat this root
 1000 A.D. – That root is heathen. Here, say this prayer.
 1850 A.D. – That prayer is superstition. Here, drink this
potion.
 1920 A.D. – That potion is snake oil. Here, swallow this pill.
 1945 A.D. – That pill is ineffective. Here, take this penicillin.
 1955 A.D. – Oops....bugs mutated. Here, take this
tetracycline.
 1960-1999 – 39 more "oops"...Here, take this more powerful
antibiotic.
 2000 A.D. – The bugs have won! Here, eat this root.
Thank you