Antibiotics for Pneumonia

8/7/2019 Antibiotics for Pneumonia

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Antibacterials forRespiratory Tract

InfectionsCecilia C. Maramba-Lazarte, MD,

MScID


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Viral Respiratory Infections

Many respiratory diseases may beviral in origin and not require anyantibiotic

Rhinovirus Adenovirus Rubeolla Coronaviruses Parainfluenza viruses


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Choice of Antibiotics forBacterial Infections

Efficacy Based on target pathogens-

local epidemiologyageseverity of illness/clinical

presentationco-morbidities

hospital acquired/communityacquiredBased on prevailing resistance patterns

in

the locality


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Bacterial RespiratoryInfectionsCommon

Diseases Pharyngitis Otitis Media

Epiglotitis Bronchitis Sinusitis

Pneumonia Lung Abscess

Common

Etiologies Group Astreptococcus

Strep

pneumoniae H. influenzae Staph aureus

Pseudomonasaeruginosa, othergram negativeorg

Anaerobes


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(%)A n tim icrob ia l R e sista n ce b y D isc,D iffu sion D O H A n tim icrob ia l

R e sista n ce S u rve illa n ce- ,Ja n D e c 2 0 0 8 Ph ilip p in e s

Ampi Chloro

Coamoxiclav

Cotri Erythro

Pen Strep

pneumoniae.

4 8 .21 7 0.H

influenzae.17 4 .20 9 .38 5

.

Mcatarrhali

s

.24 2 .17 1 .47 6 .45 9

ARI Pathogens


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(%)Antimicrobial Resistance by Disc,Diffusion DOH Antimicrobial Resistance

Surveillance- ,Jan Dec 2008 Philippines

Ampi Pen Cipro Cotri Erythro Oxa Vanco.S aureus 95.6 5.5 5.3 9.2 44.8 0

Staphylococci


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(%)Antimicrobial Resistance by Disc,Diffusion DOH Antimicrobial Resistance

Surveillance- ,Jan Dec 2008 Philippines

Amikacin Cefepime Ceftazidime

Ciprofloxacin

Gentamicin

Imipenem Netilmicin

Pipe-rTazo

Tobramycin

Pseudomonasaeruginosa

11.5 11.2 15.4 22.1 20.6 13.5 0 15.8 19.2

Ps eudom onas aer ugi nosa


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Suspected OrganismsSuspected Organisms Empiric TherapyEmpiric Therapy Alternative therapyAlternative therapy

0-2 mos0-2 mos Gram (-) baciliGram (-) bacili Ampicillin +Ampicillin +AminoglycosideAminoglycoside

33 rdrd Gen Ceph +Gen Ceph +AminoAmino

3 mos-5 yrs3 mos-5 yrs H. influenzaeH. influenzaeS.pneumoniaeS.pneumoniaeS. aureusS. aureus

MildMild AmoxycillinAmoxycillin 2nd or 32nd or 3rdrd

GenGenCephCephSevereSevere Penicillin G

VeryVeryseveresevere

ChloramphenicolChloramphenicol 33 rdrd Gen CephGen Ceph

>5 yrs>5 yrs S. pneumoniaeS. pneumoniae Pen GPen G 22 ndnd or 3or 3 rdrd GenGenCephCeph

HospitalHospitalacquiredacquired

Gram (-) bacilli, S. aureusGram (-) bacilli, S. aureus CeftazidimeCeftazidime Piperacillin-Piperacillin-tazobactamtazobactam

Recommended Antibiotics in Pediatric CAP


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Algorithm for the risk stratification of CAPamong immunocompetent adults


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Empiric Therapy for AdultCAP


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Empiric Therapy for AdultCAP


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Empiric Therapy of AdultCAP


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Review of Antibiotics


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PenicillinPenicillin Route of Use

Spectrum of Activity

Natural Penicillins Active against most streptococci,pneumococci, meningococci, oralanaerobes, spirochetes, listeria,Corynebacterium spp. poor againstgram-negative rods; susceptible tohydrolysis by -lactamases

Penicillin G, K or Na IV, IMBenzathine Penicillin IMPenicillin VK PO

Antistaphylococcus penicillins Active against staphylococci (including-lactamase producing strains) andstreptococci and most gram positivecocci; inactive against enterococci,anaerobic bacteria and Gram negativebacteria

Oxacillin IM, IVCloxacillin PO

Aminopenicillins Similar to Natural penicillins but hasactivity against some Gram negativebacteria (community acquired H.influenzae, and E.coli)

Ampicillin IV, IMAmoxicillin PO


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PenicillinPenicillin Route of Use

Spectrum of Activity

Extended spectrum penicillins Wider coverage for Gramnegative bacteria includingPseudomonas aeruginosa,active against enterococci,Bacteroides spp.

Carbenicillin

Ticarcillin IV

Piperacillin IVBeta lactam-Beta lactamase inhibitor combinationWidens coverage of basic

penicillin to include Staphaureus, increases gramnegative and anaerobiccoverage

Amoxicillin-clavulanic

acid

PO

Piperacillin-tazobactam

IV

Ticarcillin-clavulanicacid

IV


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Pharmacokinetics of Penicillins

Antibiotic OralBioavailability(%)

ProteinBinding(%)

Metabolized (%)

UrinaryRecovery(%)

Aprox.half-life inadults(hrs)

Pen G

`Pen VK

-

60-73

60

80

10-30

10-30

60-90

20-40

0.5-0.75

0.5-1AmpicillinAmoxicillinClavulanate

5074-92Well absorbed

15-182025

1017-20?

9060-7525-40

1-1.80.7-1.41

OxacillinCloxacillin

30-3550

90-9495

4520

55-6030-60

0.4-0.70.5-1

TicarcillinPiperacillin

--

45-6016

1520-30

60-8060-80

1.0-1.20.6-1.2


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Adverse effects of PenicillinsAdverse effects Frequency

%MostFrequent

GI disturbances (diarrhea, abdominalpain, vomiting)

2-5 Amp,Amox clav

Hematologic toxicity (neutropenia,platelet dysfunction, hemolyticanemia)

1-4 Pen G, Oxa,Pip

Elevated liver function test 1-4 OxaRenal toxicity (interstitial nephritis,hemorrhagic cystitis)

1-2 Meth

allergic reactions anaphylaxis, skinrashes, fever, delayed type of serum

sickness

.2-0.05 Pen G

CNS toxicity (seizures, bizarresensations)

rare Pen G


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Classif icat ion of Classif icat ion ofCephalosporinsCephalosporins

Generation Prototype Drugs Useful Spectrum*

First Cefazolin (IV)Cephalexin (PO) Gram positive Streptococci, Staph aureus;some gram negative

Second Cefuroxime (IV, PO)Cefaclor (PO)Cefoxitin (IV, IM)

Community acquired E. coli, Klebsiella,Proteus, H. influenzae, M. catarrhalis. Lessactive against gram positive bacteriaHas added activity against Bacteroides

fragilisThird Ceftriaxone (IV, IM)

Cefotaxime (IV)Cefixime (PO)Ceftazidime (IV, IM)

Enterobacteriaceae, Serratia, Neisseriagonorrhea; less active than 1 st gen againstGram positive cocci- also active against Pseudomonasaeruginosa

Fourth Cefepime (IV, IM) Comparable to 3 rd gen but more stable tolactamases of Gram negative bacteria

Fifth Ceftobiprole (IV, IM)(not FDA approved)

Activity against MRSA, Gram negativebacteria including Pseudomonas

*all cephalosporins have no activity against enterococci and listeria


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Pharmacokinetics of Selected Cephalosporins

Antibiotic OralBioavailability* (%)

ProteinBinding (%)

Metabolized (%)

UrinaryRecovery(%/hr)

Aprox. half-life in adults(hrs)

1st GenCephalexinCephradineCefazolin

9595-

10-158-1774-86

000

90/860-90/680-100/24

0.9-1.50.8-1.31.5-2.5

2nd GenCefaclor Cefuroxime axetilCefuroximeCefoxitin

9537/52--

2533-5033-5065-79

000


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Adverse effects ofCephalosporins

v Hyper sens it iv it y r eact ions- %;1 3 may cross react with

- %penici l l ins in 5 20v - - %Hematologic 1 5v - - %diarrhea 2 5v - -abn liver function tests 1%7v ( )-bil iary sludge cef tr iaxone

%20

-inters t i t ia l nephri t is rare


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Spectrum of Activity of MacrolidesDrugs Gram (+) Gram (-) OthersErythromycin S. pneumoniae,

S. pyogenes,Clostridium, S. aureus,C. diphtheriaeL. monocytogenesTreponema pallidum

N. gonorrhea,BordatellapertussisCampylobacter jejuni

Mycoplasmapneumoniae

Chlamydiapneumoniae

Chlamydiatrachomatis

Legionella

pneumophilia

Clarithromycin S. pneumoniae,S. pyogenes,Clostridium, S. aureus,C. diphtheriaeL. monocytogenes

H. influenzaeN. gonorrheaM. catarrhalisBordatellapertussis

Azithromycin S. pneumoniae,S. pyogenes,Clostridium, S. aureus,C. diphtheriaeL. monocytogenes

H. influenzaeN. gonorrheaM. catarrhalisBordatellapertussis


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Antibiotic OralBioavailability* (%)

ProteinBinding(%)

Elimination Route Aproxhalf-life(hrs)Biliary

excretionRenalexcretion

Erythromycin 30-65 70-90 Majority 2-15% 1.4-2

Clarithromycin 55 65-75 Minimal 20-40 % 3-7

Azithromycin 37 7-50 >50% 4.5% 11-14(48-96after steady

state )

Pharmacokinetics of Macrolides


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Adverse effects of

Macrol ides

.1 epigastric distress

. (2 allergic reactions fever),and rashes

.3 cholestatic jaundice.4 Cardiovascular adverse

-reactions ventricular,arrhythmias prolongation of, ,the QT interval bradycardia

and hypotension with IVadministration


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Drug Interactions withMacrolides

Macrolides are CYP1A2 andCYP3A3/4 inhibitors

increases the hepaticmetabolism of other drugsleading to increased effects and

toxicities (e.g., dicumarol,carbamazepine, digoxin,theophylline, ergot,

cyclosporine, triazolam, etc.)


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Spectrum of activity of Quinolonesaccording to Generation

Generation

Drugs Pathogens wherein Quinolone hasGood Activity

First Nalidixic acid Urinary pathogens, ShigellaSecond Ciprofloxacin,

OfloxacinGram negative(Salmonella, Shigella,E. coli, other Enterobacteriacae,Pseudomonas, H. influenzae), fewgram positive, Mycoplasma,Chlamydia, Legionella, mycobacteriaThird Levofloxacin,

Gatifloxacin*Moxifloxacin

H. influenzae, Salmonella, Shigella, E.coli, other Enterobacteriacae,Mycoplasma, Chlamydia, LegionellaStrep pneumoniae, MethicillinSensitive S. aureus, mycobacteria


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Pharmacokinetics of Quinolones

Generation Drugs T1/2(hrs)

Absorption(%)

Metabolism Excretion

First Nalidixic acid 6-7 Partiallyhepatic

Renal

Second CiprofloxacinOfloxacin

48-9

6985-95

Hepatic(includingCYP1A2)

RenalRenal

Third LevofloxacinMoxifloxacin

6-812

9986-92

RenalHepatic(glucoronideand sulfateconjugation)

RenalHepatic

Ad Eff t f


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Adverse Effects of Quinolones

nausea, vomiting, diarrhea; delirium, headache,

hallucinations, seizures; skin rashes,photosensitivity. Arthropathy has been documented in immature

animals thus damage may occur in growingcartilage in


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Drug Interactions withQuinolones

Increased serum levels of quinolones mayoccur if it is given concomitantly withprobenecid.

Quinolones enhances the anticoagulant effectof warfarin.

Antacids (with aluminum and magnesium),iron, zinc and sucralfate decreasesabsorption of quinolones.

risk of tendon rupture is increased bycorticosteroids.

Increased risk of CNS adverse effects (e.g.seizures) occurs with NSAIDS

Most 3 rd gen quinolones should be avoidedwhen the patient is given class IA (e.g.,

quinidine or procainamide) or class IIIantiarrhythmic agents (sotalol, ibutilide,


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Antibiotics for Pneumonia