Kháng sinh trong viêm phổi , ĐH Y DƯỢC TP HCM

Bài giảng dành cho sinh viên y khoa, bác sĩ đa khoa, sau đại học. ĐH Y Dược TP Hồ Chí Minh. ĐỊNH NGHĨA , CƠ CHẾ TÁC ĐỘNG VÀ PHÂN LOẠI KHÁNG SINH, PHỔ TÁC ĐỘNG CỦA KHÁNG SINH, LỰA CHỌN KHÁNG SINH ĐIỀU TRỊ VIÊM PHỔI, THỜI GIAN ĐIỀU TRỊ

ANTIBIOTIC FOR

PNEUMONIA

PGS.TS.BS PHAN HUU NGUYET DIEM

synthetic Another classification system is

based on biological activity:bactericidal agents

kill bacteria, and bacteriostatic agents slow

down or stall bacterial growth

Classification of Antibiotics

Mechanism of Action

Inhibitors of Cell Wall Synthesis

Beta Lactam Antibiotics

 Penicillins

 Cephalosporins

 Carbapenems

 Monobactams

 a group of antibiotics derived from Penicillium

fungi

 Inhibits bacterial cell wall synthesis by

binding and inactivating proteins (penicillin binding proteins) present in the bacterial cell wall

 Poor CSF penetration, but can occur if there is menengial inflammation

 Renal excretion

 Side effects: hypersensitivity, nephritis,

neruotoxicity, platelet dysfunction

Penicillin G, Penicillin V, Procain PNC, Extencilline

 Gram positive cocci & rods

Penicillines

C1 C2 C3 C4 Anti-

biotics CephalexineCephalothin

Cephazoline Cephadroxii

Cefuroxime Cefamandol Cefoxitine Cefotetan Cefaclor

Cefotaxime Ceftriaxone Cefixime Ceftazidime

Cefepime Cefpirome

Spetrum Cooci Gr (+)

Pneumo Bacille Gr(-)

Bacille Gr(-) Cooci Gr (+)

Bacille Gr(-) Pseudo

Gr (+) < C1

Gr (-) resistances

 Aztreonam

 Monocyclic beta-lactam ring & relatively resistant to

most beta-lactamases

 active against aerobic Gram negative rods, P

aeruginosa, , but have no activity against gram positive bacteria or anaerobes.

 Penetrates well into the CSF

 Not absorbed orally

 Side effects: GI, occasional skin rashes

 no cross-reactivity with PCNs

Monobactams

 renal metabolism and excretion

 addition of cilastin (Imipenem - inhibitor of

dehydropeptidase I )

 Side effects: GI upset, eosinophilia, neutropenia, lowering of seizure threshold

 Glycopeptide

 Inhibits cell wall synthesis by inhibiting

peptidoglycan synthetase

 Most gram-positive bacteria, MRSA

 Useful for beta lactam resistant infections

 Synergistic action with aminoglycosides against susceptible gram positives

 Slow CSF penetration unless there is meningeal inflammation

 Side effects: Hypotension & “Red Man Side effects:

Syndrome” if given i.v in less than 1 hour,

nephrotoxicity, ototoxicity…

nephrotoxicity, ototoxicity…

Cell Membrane Active Agents

 Polymyxins

o A group of basic peptides active against

gram-negative bacteria

• Serious infections caused by P aeruginosa, H

influenzae, E coli, A aerogenes & K pneumoniae

when other drugs are contraindicated

• Ocular infections (bacterial conjunctivitis - ophthalmic drops)

• Meningitis

o Side Effects: Nephrotoxic & Neurotoxic

Protein Synthesis Inhibitors

 Bind to 30S ribosomal subunit.

 Broad spectrum bacteriostatic & generally 2nd line drugs

 Not recommended for pregnant women, infants and

children 8 years or younger.

 Side Effects: Staining of teeth, retardation of bone

growth, GI toxicity, Photosensitivity…

 Aerobic Gram negative bacilli: Klebsiella, Serratia,

Proteus, Pseudomonas, tularemia, plague, brucellosis….

 Effective against Aerobic Gram positive cocci :

Staphylococcus, Group B Streptococcus, viridans

streptococci, Enterococcus

 Mycobacteria – tuberculosis

 N gonorrhoeae

 Not effective against anaerobes

 AGs are not recommended as monotherapy for severe infections, but must be combined with another agent

 Used in combination with vancomycin or a penicillin for enterococcal endocarditis, and for treatment of

tuberculosis

Exp: CSF

 Spectrum: Staph., S pyogenes and S

pneumoniae, Legionella and H.pylori

Chlamydia, Mycoplasma (Clinically useful in penicillin hypersensitive patients)

 Preoperative bowel preparation (oral

administration of erythromycin base).

 A drug of choice for Legionnaire's

disease , but is now a 2nd line drug for

other susceptible bacteria.

 Use is limited due to increasing resistance.

 Commonly used for respiratory tract & sinus infections

 Treatment of infections by Helicobacter

Mycobacterium avium complex (MAC)

 Respiratory tract infections

 Skin infections (SSTIs)

 Traveler's diarrhea

Macrolides

 Binds to 50S ribosomal subunit and inhibits

peptidyl transferase and blocks protein synthesis

 Most frequently used outside of the United States Rarely used within the US because of concerns about aplastic anemia.

 Broad spectrum Neisseria meningitidis,

Clostridium perfringens, Bacteroides,

Hemophilus influenzae (bactericidal effect in this sensitive organism), Salmonella typhi and

Rickettsia

difficile

Clindamycin

Inhibitors of Nucleic Acid

SparfloxacinTosufloxacinTrovafloxacin

Spectrum Shigella Gr (-) enteric

Gr (-) mulitiresisExp: Anerobic

Anerobic

Inhibitors of Nucleic Acid

Function/Synthesis

Co-Trimoxazole (TMP/SMX)

 Bacteriostatic

 Spectrum

 Staph aureus (esp MRSA)

 Gram-negative bacilli: Enteric bacteria such as E coli

(e.g cystitis - Urinary Tract Infections )

 Listeria

 Pneumocystis jirovecii (PCP)

 Parasites: Isospora belli, Cyclospora cayatenensis

 Side Effects: Hypersensitivity (Stevens-Johnson Syndrome), Nephrotoxicity, Hepatitis, hemolytic anemia (G-6-P deficiency)

 Contraindicated in new borns and during last two months of pregnancy

Mycoplasma

Resistance to Antibiotics

Classification of pneumonia (WHO)

 Children aged 2–59 months:

with cough or difficulty breathing accompanied by tachypnea.

indrawing or central cyanosis), stridor when calm,

or IMCI-defined danger signs (inability to drink or breastfeed, convulsions, persistent vomiting,

lethargy, or unconsciousness).

pneumonia have, by definition, severe

pneumonia

children with pneumonia who need

antimicrobial therapy.

Indicators for admission to hospital

appropriate care and assure compliance with the

therapeutic.

an infant.

breaths/min in infants <12 months or >50 breaths/min in older children, difficulty breathing, apnea, grunting.

metabolic disorder, immunocompromised host).

in 24 to 72 hours).

COMMUNITY ACQUIRED

PNEUMONIA

defined as an acute infection of the

pulmonary parenchyma in a patient who has acquired the infection in the

community (Likely organisms: Strep

HOSPITAL ACQUIRED (NOSOCOMIAL) PNEUMONIA

infection that was not present or incubating

at the time of admission to the hospital

(pneumonia developing >48 hours from

admission to the hospital) (Likely

organisms depend on the clinical situation,

multi-resistant Gram negative bacilli or positive cocci).

Outpatient treatment of CAP (WHO recommendations)

 First-line treatment: amoxicillin is 50 mg/kg

per day in two divided doses for a 3-day

treatment course in areas with low HIV

prevalence, and 5 days in areas of high HIV prevalence.

evidence clearly indicates infrequent

resistance, co-trimoxazole (8 mg/kg

trimethoprim in two divided doses) may be an acceptable alternative.

Outpatient treatment of CAP (WHO recommendations)

 Treatment failure is defined as the

development of lower chest-wall

indrawing, central cyanosis, stridor while calm, or IMCI-defi ned danger signs at any time during achild’s illness or a

persistently raised respiratory rate at 72 h (48 h in an area of high HIV prevalence).

 Causes: Wrong diagnosis, Host failure,

Complication, Non-susceptible pathogen

Outpatient treatment of CAP (WHO recommendations)

 High-dose amoxicillin with clavulanic acid (80–90 mg/kg per day amoxicillin) for

second-line A 5-day treatment course

should be prescribed.

 For children over 3 years of age, an aff

ordable macrolide or azalide (eg, 50 mg/kg erythromycin in four divided doses for 7

days) may be added to the existing regimen for a 5-day or 7-day treatment course.

 Children failing first-line treatment with trimoxazole, the recommendation is to

co-switch to a 5-day course of amoxicillin (50

mg/kg).

Outpatient treatment of CAP

(UpToDate 2010)

hypoxemic should be admitted to the

hospital.

likely bacterial pathogen is C.trachomatis

three days)

divided every six hours for 14 days)

Outpatient treatment of CAP

(UpToDate 2010)

 4 months to 4 years

 Viral pneumonia — Viral etiologies predominate

 Bacterial pneumonia — Streptococcus

pneumoniae is the most frequent cause of

"typical" bacterial pneumonia in children of all ages

 M pneumonia and C pneumonia- less common causes of pneumonia, but should be considered

in children who fail to improve after 24 to 48

hours of amoxicillin therapy, at which time a

macrolide could be added or substituted

Outpatient treatment of CAP

(UpToDate 2010)

 Children ≥ 5 years:

 Amoxicilline 80 to 100 mg/kg per day by mouth

in three divided doses (maximum dose 2 to 3 g/day) for 7 to 10 days

 Non-type 1 hypersensitivity reactions to

penicillin: cefdinir (14 mg/kg per day in one or

two divided doses; maximum dose 600 mg per day)

 Type 1 hypersensitivity reactions to penicillin: clindamycin or a macrolide

 if local resistant rates are high for both of these agents, linezolid may be preferable

Outpatient treatment of CAP (UpToDate 2010)

 Clarithromycin (15 mg/kg per day divided every 12

hours; maximum dose 1 g/day), or

 Azithromycin (10 mg/kg administered once on day one [maximum dose 500 mg] followed by 5 mg/kg once daily

on days two to five [maximum dose 250 mg/day]), or

 Linezolid (10 mg/kg every 8 hours for children <12 years

of age, and every 12 hours for children ≥12 years, with the maximum individual dose of 600 mg)

Outpatient treatment of CAP

(UpToDate 2010)

 For the infant or child who is suspected to have bacterial CAP and is unable to

tolerate liquids at the time of presentation,

a single initial dose of ceftriaxone (50 to

75 mg/kg) may be administered

intramuscularly or intravenously before

starting oral antibiotics

Outpatient treatment of CAP

(UpToDate 2010)

pneumoniae are the most likely

pathogens Macrolide are the treatment of choice

 For children ≥8 years, doxycycline is an

alternative (4 mg/kg per day in two divided doses; maximum 200 mg/day)

macrolides: high-dose amoxicillin (80 to

100 mg/kg per day) , cephalosporin,

fluoroquinolones

Outpatient treatment of CAP

 Clindamycin (30 to 40 mg/kg per day,

divided every six to eight hours; maximum

1 to 2 g/day)

Outpatient treatment of CAP

(UpToDate 2010)

 Duration:

 In older infants and children, 7 to 10 days should be adequate for routine pathogens causing uncomplicated infection; the

course of azithromycin is five days.

 In young infants being treated for afebrile pneumonia of infancy, the duration of

therapy is 14 days for erythromycin and 3 days for azithromycin.