Transcript antimicrobial spectra

EMERGING AND
REEMERGING DISEASES
Emerging infectious diseases
Emerging infections
Associated diseases
Bartonella henselae
Ehrlichia caffeensis/equi
Fakeeh virus
Hepatitis G virus
Human herpesvirus-8
Andes virus, Bayou virus Laguna
negra virus, New York virus, Oran
virus
Nipah virus
Helicobacter pilory
Nontuberculous mycobacteria
Prion protein
Cryptosporidium, Cyclospora,
Microsporidia
Cat-scratch disease
Human monocytic/granulocytic
ehrlichiosis
Haemorrhagic fever in Saudi Arabia
Uncertain significance
Kaposi’s sarcoma
Hantavirus pulmonary syndrome
South/North America
Encephalitis
Gastritis/ulcer
Infections in HIV patients
New variant Crewtzfeld-Jacob disease
Gastroenteritis
in
Resurgent infectious diseases
Disease agent
Associated disease
Borrelia burgdorferi
Dengue virus
Ebola
Echerichia coli O157:H7
Lyme disease
Dengue haemorrhagic fever/shock
Haemorrhagic fever in
Gabon/Congo
Gastroenteritis/haemolytic uraemic
syndrome
Encephalitis in Nepal
Visceral leishmaniasis
Haemorrhagic fever
Haemorrhagic fever
Haemorrhagic fever
Encephalitis in Italy
Plague
Japanese encephalitis
Leishmania donovani
Machupo virus
Marburg virus
Rift valley fever virus
Toscana virus
Yersinia pestis
Infectious diseases wil continue to emerge, reemerge and submerge, but continuing
advances in diagnostics, surveil ance, therapeutics and vaccines may be very important in
prevention and control.
Finally, we must be prepared for the unpredictable and unexpected, as was the case with the
emergence of AIDS.
PATHOGENESIS OF BACTERIAL INFECTION
The virulence of pathogen
The fitness of a pathogen can be defined as its ability to multiply within a host, disseminate
from that host, translocate to a new host, colonize the new host, and cause infection. This
can be distinguished from the virulence from a pathogen, which refers to the severity of
clinical illness resulting from infection.
Characteristics of bacteria that are pathogens include:
1. Transmissibility: from animal to humans/from human to human
 By food products to humans: Salmonella, Campylobacter
By the fleas to humans: Yersinia pestis
By animal products(raw hair): bacillus anthracis
By ingestion: C. botulinum
When wounds are contaminated by soil:C. perfringens and C. tetani.
From one person to another by hands: S. aureus
The most frequent portal of entry of pathogenic bacteria are:
- respiratory
- gastrointestinal
- genital
- urinary tracts
2. Adherence to host cells
Once in the body bacteria must attach to host cells, usually epithelial cells
They multiply and spread directly through tissues or via the lymphatic system to the
blood stream
Adherence factors:
 Surface hydrophobicity and net surface charge (the more hydrophobic the
bacterial cell surface, the greater the adherence to the cell surface
 Specific surface molecules
-pili( eg. E. coli)
-fimbriae (group A Streptococci); lipoteichoic acid and M protein are found on
the fimbriae.
3. Invasion of host cells and tissues
This is a term commonly used to describe the entry of bacteria into host cells.
Examples:
- Shigella adhere to host cells, induces the formation of pseudopods and
engulfment of the bacteria. Once inside the cells, the shigellae either are released,
or escape from the phagocytic vesicle, where they multiply in the cytoplasm
(similar for Yersinia enterocolitica.
- Legionella pneumophila - infects pulmonary macrophages and cause
pneumonia. The agent induces formation of a thin pseudopod, that coils around
the bacteria forming a vesicle. Phagolysosome fusion is inhibited and the bacteria
multiply within the vesicle.
Toxigenicity
EXOTOXINS
ENDOTOXINS
Excreted
by
living
cells;
high
concentrations in liquid medium
Produced by both GP and GN bacteria;
Polypeptides;
Relatively unstable; toxicity often
destroyed rapidly by heating(>60 C);
Highly antigenic; stimulate formation of
antitoxin. Antitoxin neutralizes toxin;
Converted to antigenic, nontoxic toxoids
by formalin, acid, heat. Toxoids are used
to immunize(tetanus toxoid);
Highly toxic(fatal in microgram
quantities);
Usually bind to specific receptors on
cells;
Usually do not produce fever
Controled by extrachromosomal
genes (plasmids)
Part of the cell wall of gram-negative
bacteria. May not need to be released to
have biologic activity;
Only in gram negative bacteria;
Lipopolysacharide complexes;
Relatively stable, without loss of toxicity for
hours if >60 C;
Weakly immunogenic; antibodies
antitoxic and protective;
Non converted to toxoids
Moderately toxic;
are
Specific receptors not found in cells;
Produce fever by release of IL1 and other
mediators
Synthesis directed by chromosomal genes
5. Ability to evade the host’s immune system
Enzymes: coagulase, beta-lactamases, streptokinases
METHODOLOGIES USED IN THE
DIAGNOSIS OF INFECTIOUS DISEASES
The methods of diagnosis used for the diagnosis of infectious diseases are as
follows:
I. Serology: requires a diagnostic titer or evidence of conversion by four-folds
increase in titer of antibodies:
 Complement fixation (CF) –
 Neutralizing antibody titer (NA) -;
 Hemagglutination inhibition (HI) –
 Precipitating reaction (when soluble antigen comes in contact with its
corresponding antibody in solution, antigen-antibodies complexes result, which are
insoluble) -.
 Immunofluorescence and immunoenzyme procedures –Radioimmunoassay and
enzyme immunoassay –
II. Direct detection by:
II. Direct detection by:
1. Special stains: Gram stain, acridine orange, mycobacterial stains (ZiehlNeelsen, fluorochrome stain),.
2. Antigen detection by:
a. latex agglutination – for CSF specimens, fungal antigens
b. enzyme immunoassay (ELISA)– for bacterial antigens (group A sterptococcus,
Legionella), bacterial toxins (toxins of E.coli, Clostridium difficile), fungal
antigens, parasitic antigens (Giardia lamblia, Cryptosporidium), viral antigens
(Herpes simplex, influenza A, adenovirus, respiratory syncitial virus), chlamydial
antigens.
c. Counter immune electrophoresis (CIE)
3. Molecular based assays:
a. Hybridization with DNA probe (detect specific ribosomal DNA)
b. Amplification assays such as those using PCR (polymerase chain reaction) or
ligase chain reaction.
III. Detection by culture and:
a. identification by biochemical reactions (ex. coagulase test)
b. identification by specific antisera by agglutination or fluorescent antibody test
c. identification using molecular-based methods (specific probes, restriction
enzyme pattrern, DNA sequencing)
 antimicrobial susceptibility testing.
Specific susceptibility testing procedures
a. Disk diffusion susceptibility testing
b. Minimal inhibitory concentration testing
c. Testing for bactericidal activity
d. Serum bactericidal test
e. Synergy testing.
IV. Skin tests
1. Toxin neutralization
2. Delayed hypersensitivity –.
ANTI-INFECTIVE THERAPY
Antibiotics are bacterial or fungal products, or are obtained by
synthesis, which are capable of inhibition or destruction of some
microbiological species.
The modern era of chemotherapy begins with the discovery of
sulphonamides in 1936, followed immediately, in the 1940s, by the
discovery of the therapeutic properties of penicillin and streptomycin.
Principles of anti-infective therapy
Choice of the proper antimicrobial agent
1.Identification of the infecting organism, or, if it is impossible to determine
the exact nature of the organism, may be useful to use bacteriologic statistic
(application of knowledge of the etiology most likely to cause an infection in
a given clinical setting);
2.Determination of antimicrobial susceptibility of etiological agent
(sensitive, intermediate sensitive, resistant);
3.Identifying host factors that may influence the efficacy and toxicity of
antimicrobial agents:
a.History of previous adverse reactions to antimicrobials
b.Age (ex. creatinine clearence may be reduced in elderly)
c.Genetic or metabolic abnormalities
d.Pregnancy
Antimicrobials in pregnancy
Antibiotic
I-st trimester
II-nd
trimester
III-rd
trimester
Penicilline
Cephalosporins
Macrolides
Polipeptides
Tetracyclines
Aminoglycoside
s
Phenicoles
Rifampicine
Sulphonamides
Quinolones
Nitrofurantoin
Imidazoles
+
+
+
+
-
+
+
+
+
+
+
+
+
+
+
+
+
+
e.Renal and hepatic function (the major routes of drugs elimination)
Creatinine clearence (ml/min)=(14—Age in years) x weight in kg/serum Creatinine
in mg/dlx72.
f.Site of infection..
4.Antimicrobial combination may be justified in the following situations:
When suspected polymicrobial infections (intraperitoneal, pelvic infections, etc)
To prevent emergence of resistance (tuberculosis, with antibiotics such as
vancomycin, aminoglycosides, fosfomycin)
To obtain synergism (ex. penicillin + aminoglycosides for enterococci infections)
Initial therapy in neutropenic patients, or, when exact nature of infection is not
clear)
To decrease toxicity
5.Choice of appropriate route of administration for antimicrobials:
-intravenous therapy
-oral absorption may be decreased
6.Pharmacologic properties of antimicrobials.
7.Monitoring the response of the patient to antimicrobial therapy:
-determination of serum concentration of antimicrobial agents
-determination of serum bactericidal titer
PENICILLINS
Classification of penicillins :
1.Natural penicillins
2.Penicillinase resistant penicillins (Methicilline
group)
3.Aminopenicillins (“A” Group)
4.Antipseudomonal penicillins (carboxipenicillins
and ureidopenicillins)
NATURAL PENICILLINS
Doses of natural
penicillins
DOSEADULT/DAY
DOSE-CHILD/DAY
DRUG
PENICILLINE G
PENICILLINE V
EXTENCILLINE
(BENZATHINE
PEN G)
1-20 mil.UI, im/iv,
4/6/12h
3-4 mill.U,po , 6/8h
1,2 mill. U/15 days
or
2,4 mill.U/month
50000-200000 U/kg
50000-100000 U/kg
600000 U/15 days or
1,2 mill.U/month
Antimicrobial spectra and therapeutical indications of natural penicillins
ANTIMICROBIAL SPECTRA
1.Streptococcus group A, B, C,
D
2.Str. pneumoniae
3.Str. viridans
4.N. meningitidis
5.C. diphteriae
6.B. anthracis
7.Clostridium (ex. C. difficile)
8.Peptostreptococcus sp
9.Treponema pallidum
10.Leptospira
11.Borrellia
12. Listeria monocytogenes
INDICATIONS
Tonsillitis, Scarlet fever(1)
Pneumonia, meningitis, sepsis
(2)
Endocarditis(3)
Sepsis, meningitis (4)
Anthrax (6)
Diphteria (5)
Syphillis (9)
Leptospirosis (10)
Lyme disease(11)
Meningitis, sepsis (12)
PENICILLINASE-RESISTANT PENICILLINS
Antibacterial spectra: Staphylococcus aureus (Methicil in-sensitive)
Indications: localised / generalised staphylococcal infections
Doses of penicil inase - resistant penicil ins
DRUG
DOSE-ADULT
DOSE-CHILD
OXACILLIN/
NAFCILLIN
CLOXACILLIN
DICLOXACILLIN
2-4g/d
50-100 mg/day
(po:6/8h;im,iv:4-12h) 100-200 mg/kg/day
4-12g/d (im,iv:4-6h) 50-100 mg/kg
1-4 g/d (6-8h)
AMINOPENICILLINS
Table 4. Doses of aminopenicillins
DRUG
DOSE-ADULT
DOSE-CHILD
AMPICILLIN
Po: 2-4 g/day
Im,iv:4-12 g/day
Po,im,iv:1-8 g/d
0,8-2,4 g/d
2-12 g/d
1-3 g/d
2-3 g/d
3-4,5 g/d
100 mg/d
100-300 mg/d
25-200 mg/kg
50-100 mg/kg/d
50-200 mg/kg/d
50-100 mg/kg/d
30-40 mg/kg/d
30-40 mg/kg/d
AMOXICILLIN
BACAMPICILLIN
METAMPICILLIN
PIVAMPICILLIN
AMOXICILLINclavulanic acid
AMPICILLIN-sulbactam
The antimicrobial spectra and indications:
Enterococcus  endocarditis
Streptococcus gr. A,B,C,G  prophylaxis of stomatologic infections
S. pneumoniae  pneumonia, meningitis, sepsis
N. meningitis meningitis, sepsis
L. monocytogenes  meningitis, sepsis
Borrellia meningitis.
ANTIPSEUDOMONAL PENICILLINS (CARBOXY AND UREIDOPENICILLINS)
Doses of antipseudomonal penicillins
DRUG
DOSE-ADULT
DOSE-CHILD
TICARCILLINE
TICARCILLINE+
clavulanic acid
MEZLOCILLINE
PIPERACILLINE
PIPERACILLINE+
tazobactam
250 mg/kg/d
12,4-18,6g/d
6-15 g/d
6-15 g/d
4,5-13,5 g/d
75-100 mg/kg/d
150-300mg/kg/d
100-300 mg/kg/d
100-300 mg/kg/d
100-300 mg/kg/d
Antimicrobial spectra and indications of antipseudomonal penicil ins
ANTIMICROBIAL SPECTRA OF
ANTIPSEUDOMONAL
PENICILLINS
INDICATIONS
TICARCILLINE:
Proteus
Enterobacter
Serratia
Pseudomonas
PIPERACILLINE: “AMPI” spectra +
Serratia marcescens
Enterobacte cloacae
Citrobacter
Bacteroides fragilis
Pseudomonas
Proteus
Severe infections with sensitive
germes
Plurimicrobial infections: biliary,
digestiv, genito – urinary tract
MONOBACTAMS
AZTREONAM
Dose: 1g/day, i.v. in Gram negative cocci and bacilli infections.
Adverse reactions: allergies, hepatotoxicity, disulfiram-like
syndrome.
CARBAPENEMS
Doses of carbapenems
DRUG
ADULT
CHILD
IMIPENEM
MEROPENEM
2 g/d
3 g/d
30-60 mg/kg/d
40 mg/kg/d
Antimicrobial spectra and indications of carbapenems
ANTIMICROBIAL SPECTRA
GP COCCI (except Methicillin-Resistant-S.
aureus)
*GNBACILLI(Ps.aeruginosa, Acinetobacter)
*GP ANAEROBES
*GN ANAEROBES(Bacillus fragilis)
*
GP=gram positive, GN=gram negative
INDICATIONS
Severe inf. with multi resistant germs
nosocomial infections
Pluribacterial infections
CEPHALOSPORINS
1st GENERATION CEPHALOSPORINS
Doses of 1 st generation cephalosporins
DRUG
DOSE-ADULT
DOSE-CHILD
CEFACLOR
2-4 g/d po
50-100 mg/kg/d
CEFADROXYL
2-4 g/d po
50-100 mg/kg/d
CEFALEXINE
2-4 g/d po
50-100 mg/kg/d
st
Antimicrobial spectra and indications of 1 generation cephalosporins
ANTIMICROBIAL SPECTRA
INDICATIONS
S.pneumoniae
Respiratory infections
Streptococcus
(except enterococcus)
Urinary infections
Skin infections
Meti-S Staphylococcus
2nd GENERATION CEPHALOSPORINS
Doses of 2nd generation cephalosporins
DRUG
DOSE-ADULT
DOSE-CHILD
CEFAMANDOLE
CEFUROXIME
CEFPROZIL
Cephamycines
CEFOTETAN
CEFOXITIN
3-6 g/d
1,5-4 g/d
500 mg/d, po
50-100 mg/kg/d
50mg/kgq8hiv,1015mg/kg bid po
10-15mg/kg bid (max 1
g/d)
2-6 g/d, iv
3-6 g/d, iv
30-60 mg/kg/d
50-100 mg/kg/d
nd
Antimicrobial spectra and indications of 2 generation cephalosporins
ANTIMICROBIAL SPECTRA of 2nd
gen. CS
1st gen. cephalosporins – spectra + :
 H. influenzae
 N. gonorrhoeae
 E. coli, Klebsiella
For cefoxitine: GN anaerobes
INDICATIONS
Otitis
Sinusitis
Tonsilitis (if failure with
penicillin G, or
reccurences)
Antimicrobial spectra and indications of 3 rd generation cephalosporins
ANTIMICROBIAL SPECTRA of 3rd
gen. CFS
Enhanced activity vs. AEROBIC GN
BACTERIA:
E. coli, Shigella, Proteus, Salmonella
Inconsistant activity vs.:
Serratia, Pseudomonas, Acinetobacter,
Enterobacter
Modest activity against ANAEROBES
(only for CEFTIZOXIME)
Antipseudomonal activ.:
CEFTAZIDIME
Less active than 1st G.CFS. vs. GP
COCCI
INDICATIONS
SEVERE INFECTIONS :
Sepsis
Broncho-pneum.
Nosocomial infections
Surgery
antibioprophylaxis
4th GENERATION CEPHALOSPORINS
rd
CEFEPIME: 1-2 g q12h, i.v. activity vs. Gram positive cocci  3 Generation
CFS
CEFPIROME: enhanced activity vs. Enterobacteriaceae and P. aeruginosa.
LINCOSAMIDES
Doses of lincosamides
DRUG
DOSE-ADULT
DOSE-CHILD
CLINDAMYCINE
0,6-2,4 g/d, po, im, iv
(every 6-8h)
8-25 mg/kg, po
15-40mg/kg,
parenterally
LINCOMYCINE
0,6-1,8g im., iv po
(8h)
30-60 mg/kg/d, po
10-20 mg/kg/d, im/iv
THE ANTIMICROBIAL SPECTRA is represented by:
Anaerobic bacteria (Gram positive and gram-negative)
 Staphylococcus
 Streptococcus (excepting enterococcus)
THERAPEUTICAL INDICATIONS are:
 Bone and joint infections
 Infections with anaerobes (without meningitis!)
 Prophylaxis of infective endocarditis (if allergy to Penicillin is present).
AMINOGLYCOSIDES
Doses of aminoglycosides
DRUG
DOSE-ADULT
DOSE-CHILD
1. AMIKACINE
2. DIBEKACINE
3. GENTAMYCINE
4. NETILMYCINE
5. SISOMYCINE
6. TOBRAMYCINE
7. KANAMYCINE
8. STREPTOMYCINE
9. ISEPAMYCINE
15 mg/kg/d (12-24h)
3 mg/ kg/d (12-24h)
3 mg/kg/d (8, 12, 24h)
4-7 mg/ kg/d (8, 12, 24h)
3 mg/ kg/d (8, 12, 24h)
3-5 mg/ kg/d (8, 12, 24h)
15 mg/kg/d (12h)
0,5-1 g/d (24h)
15 mg/kg q24h
15 mg/kg/d
2-4 mg/kg/d
6-9 mg/kg/d
3-5 mg/kg/d
3 mg/kg/d
15mg/kg/d
30-50 mg/kg/d
-
3rd GENERATIONS CEPHALOSPORINS
rd
Doses of 3 generation cephalosporins
DRUG
DOSE-ADULT
DOSE-CHILD
CEFOPERAZONE
CEFOTAXIME
CEFTAZIDIME
CEFTRIAXONE
CEFTIZOXIME
LATAMOXEF
Oral
CEFIXIME
CEFPODOXIME
CEFTIBUTEN
CEFDINIR
4 g/d
4-6 g/d
3-6 g/d
2-3 g/d
3-12 g/d
2-6 g/d
30-60 mg/kg/d
50-100 mg/kg/d
50-100 mg/kg/d
50-75 mg/kg/d
30-60 mg/kg q8h
400 mg/d po
200-400 mg/d
400 mg/d
600mg/d
8 mg/kg/d div bid
10mg/kg div bid
4,5 mg/kg bid
Antimicrobial spectra and indications of aminoglycosides
ANTIMICROBIAL SPECTRA of
aminoglycosides
NETIL.,GENTA.,TOBRA.,SISO.,DIBE
KA:
- Staphylococcus
- E.coli
- Listeria monocytogenes
Inconstantly: Proteus, Klebsiella,
Enterobacter, Serratia
AMIKA:
- Staphycoccus
-Aerobes GN bacilli: E.coli,Serratia
Enterobacter, Proteus, Pseudomonas,
Klebsiella
Acinetobacter
STREPTOMYCINE:
My. tuberculosis, Brucella
KANA: M. tuberculosis
INDICATIONS
! IN ASSOCIATION !
URINARY INFECTIONS.
INFECTIVE ENDOCARDITIS
SEVERE
INFECTIONS
WITH
STAPH/GN BACILLI
INFECTIONS WITH LISTERIA
INFECTIONS
WITH
MULTIRESISTANT GERMS
BRUCELLOSIS
TUBERCULOSIS
TETRACYCLINES
Doses of tetracyclines
DRUG
1st Generation:
TETRACYCLINE
OXYTETRACYCLINE
ROLITETRACYCLINE
2nd Generation:
LYMECYCLINE
METACYCLINE
3rd Generation:
DOXICYCLINE
MINOCYCLINE
DOSE-ADULT
DOSE-CHILD
25-30 mg/kg (6-8h), 50 mg/kg
po
10-20 mg/kg
250-500 mg (1224h),im
300mg,im
10-15 mg/kg
10-30 mg/kg (12h)
10-30 mg/kg (12h)
200 mg (1st day),then
100 mg
200 mg (1st day),then
100 mg
2-4 mg/kg
2-4 mg/kg
Antimicrobial spectra and indications of tetracyclines
ANTIMICROBIAL SPECTRA
of tetracyclines
N. gonorrhoeae, Yersinia
Brucella
Pasteurella
Legionella pneumophila
Vibrio cholerae
Erlichia canis
Mycoplasma pneumoniae
Rickettsiae
Chlamydia
Treponema
Borrelia
INDICATIONS
BRONCHO-PULMONARY
INFECTIONS,
BRUCELLOSIS,
CHOLERAE,
GENITAL INFECTIONS WITH
CHLAMYDIA.
MACROLI
D
ES
Doses of macrolides
DRUG
“old” macrolides:
ERYTHROMYCINE
SPIRAMYCINE
JOSAMYCINE
“new” macrolides:
CLARITHROMYCINE
DIRITHROMYCINE
ROXITHROMYCINE
Azalides:
AZITHROMYCINE
SINERGISTINES:
PRISTINAMYCINE
VIRGINIAMYCINE
DOSE-ADULT
DOSE-CHILD
2-3 g/d po, iv
2-3 g/d; 4,5-9 mil.UI/d
1-2 g/d
25-50 mg/kg/d
50000 UI/k/d
30-50 mg/k/d
0,5-2 g/d, po
0,5 mg/d, po
300 mg/d
300-600 mg/d
5-8 mg/k/d
500 mg/d, po
10 mg/kg/d
3 g/d, po
3g
50-100 mg/kg
50-100 mg/kg
Antimicrobial spectra and indications of macrolides
ANTIMICROBIAL SPECTRA of Macrolides
Streptococcus A,C,G
Staphilococcus methicillin-Sensitive
Moraxella catarrhalis
Bordetella pertussis
Corynebacterium diphteriae
Erysipelotrix
Campylobacter
Treponema
Legionella
Mycoplasma
Chlamydia
Rickettsia
GN cocci
Toxoplasma gondii ( SPIRAMYCINE,
CLARITHROMYCINE)
Atypical Mycobacteria
Bartonella
ROXITHRO,
INDICATIONS
BRONCHITIS
ATYPICAL PNEUMONIA,
PNEUMONIA WITH LEGIONELLA,
SKIN INFECTIONS,

ENTERAL INFECTIONS
(YERSINIA, CAMPYLOBACTER,
CRYPTOSPORIDIUM),
GENITAL INFECTIONS,
TOXOPLASMOSIS (pregnancy),

BACILLARY ANGIOMATOSIS,
HEPATIC PELIOSIS
INFECTIONS IN STOMATOLOGY
GLYCOPEPTIDES
Doses of glycopeptides
DRUG
ADULT
CHILD
VANCOMYCIN
1,5-2 g iv (12h)
TEICOPLANIN
200-400 mg/d
0-30 days (age): 15 mg/kg/d
> 30 days (age): 10 mg/kg/d
10 mg/kg/d
The spectra includes:
-Methicillin-resistant Stafilococcus aureus (MRSA)
-Penicillin-resistant Streptococcus pneumoniae (PRP)
-Enterococcus
-Clostridium difficile
CHLORAMPHENICOL
The drug is bacteriostatic for the majority of organisms listed in the following table, but it is bactericid for
the germes involved in meningitis: N. meningitidis, S. pneumoniae, H. influenzae.
Doses:
>28 days old: 12,5-25 mg/kg q6h;
older children and adults: 50 mg/kg/day (in 6 hourly intervals);
older children and adults with meningitis: 100mg/kg/day (in 6 hourly intervals).
Antimicrobial spectra and indications of chloramphenicol
ANTIMICROBIAL SPECTRA
GP cocci:
S. aureus
S. epidermidis
S. pneumoniae
Peptococcus-Peptostreptococcus
GN cocci and coccobacilli:
N. gonorrhoeae
Pasteurella multocida
H. influenzae
Brucella spp
Bordetella pertussis
GP bacilli:
Corynebacterium diphteriae
Listeria monocytogenes
Clostridium spp
Prpionibacterium acnes
Actinomyces israelii
Actinobacillus actinomycetemcomitans
GN bacilli:
E. coli, S. typhy, and Proteus mirabilis
Enterobacteriaceae have varying sensitivities)
Chlamydia, Mycoplasma, rickettsies
INDICATIONS
BRAIN ABSCESS
SUBDURAL EMPIEMA
MENINGITIS
TYPHOID FEVER
RICKETSIAL
INFECTIONS
(the
other
QUINUPRISTIN AND DALFOPRISTIN
Dose: 7,5 mg/kg i.v. (q 8h)
Antimicrobial spectra and indications of quinupristin and dalfopristin
ANTIMICROBIAL SPECTRA of
Quinupristin and dalfopristin
E. faecium
S. aureus (including MRSA)
S.pneumoniae (including PRP)
Lactobacillus spp,
Leukonostoc spp
Bacteroides spp
Moraxella
L. monocytogenes
Prevotella
My. pneumoniae
INDICATIONS
Skin infections
Hospital aquired pneumoniae
Urinary tract infections
Bone and joint infections
Endocarditis
Catheter-related bacteremia
Adverse reactions: local pain, inflammation, phlebitis, gastrointestinal manifestations.
METRONIDAZOLE AND OTHER NITROIMIDAZOLES
Dose depends upon the infection:
Giardiasis: 250 mg bid 5-7 days, or 2g/day 3 days.
Susceptible anaerobic infection:
i.v. - 15 mg/kg then 7,5 mg/kg q6h
p.o. – 1-2 g/d in 2-4 doses .
Antimicrobial activity: Bacteroides fragilis, B. melaninigenicus,
Prevotella, Fusobacterium spp, anaerobes gram-negatives cocci and
gram-positive cocci, Cl. perfringens, Giardia lamblia, Entamoeba
histolytica, Trichomonas vaginalis
Tinidazole is effective as single dose regimen for treatment of
trichomoniasis and giardiasis.
Other nitroimidazole compounds are ornidazole, carnidazole and
secnidazole.
FOSFOMYCINE
Fosfomycine is active against Staphylococcus (even the methicillin-resistant
Staphylococcus) and Gram negative bacilli.
Recommended doses:
- 8-12 g/d, iv (adults)
- 100-200 mg/kg/d (child)
FLUOROQUINOLONES
Classification and antimicrobial spectra of fluoroquinolones
Biologic classification of fluoroquinolones
Microbiologic classification
GroupI: Limited spectrum
Nalidixic acid
Flumequine
Oxolinique acid
Piromedique acid
Pipemidique acid
Cinoxacine
ENTEROBACTERIACEAE
Group II: Large spectrum
Pefloxacin
Enoxacin
Norfloxacin
Ciprofloxacin
Fleroxacin
Lomefloxacin
Ofloxacin
Enterobacteriaceae and:
H. influenzae
Neisseria spp
Coagulase negative staphylococcus
Intracellular pathogens
Mycoplasma spp
P. aeruginosa
Acinetobacter spp
Vibrio holerae
M. tuberculosis
M. leprae
Group III: Extended spectrum
Temafloxacin, Tosufloxacin, MoxifloxacinGrepafloxacin
Clinafloxacin, Gemifloxacin, Trovafloxacin, Levofloxacin
GatifloxacinSitafloxacin
Gpoup II spectra +
S. pneumoniae
Streptococcus spp+/ANAEROBES
Caution for the use of FQ in children
KETOLIDES
The most prominent member of ketolides used in therapy is TELITHROMYCINE.
The antibiotic spectrum includes:
Gram – positive cocci , including: Macrolides – resistant -Streptococcus pyogenes, S.
aureus, S. pneumoniae
Gram – negative pathogens: H. influenzae, Moraxella catarralis
Legionella pneumophila
Mycoplasma pneumoniae
Chlamydia pneumoniae
OXAZOLIDINONES
Oxazolidinones belongs to a new family of antimicrobial agents.
The first compound introduced in therapy is LINEZOLID.
The spectrum of activity is mainly represented by
GRAM – POSITIVE BACTERIAL PATHOGENS:
Methicillin – resistant S. aureus (MRSA)
S. epidermidis
Penicillin – resistant pneumococci (PRP)
Vancomycin – resistant enterococci (VRE)
Vanco – intermediate strains (VISA)
Indications:
Community and hospital – acquired pneumonia
Skin infections
Other infections with gram positive – resistant germs.
Dose: 600 mg. x 2 / day, or 25 mg/kg/day
Excretion: Liver 70% + Renal 30%.
SULFONAMIDES AND TRIMETHOPRIM
Antimicrobial spectra of sulfonamides
DRUG
Sulfadiazine
Sulfisoxazole
Sulfametoxazole
Sulfadoxine
ANTIMICROBIAL ACTIVITY
Gram positive organisms
(S. aureus, S. pneumoniae, S.
pyogenes, Enterococcus fecalis,
Corynebacterium diphteriae, Listeria
monocytogenes, Bacillus antracis)
Gram negative organisms (E. coli,
Klebsiella, Salmonella, Serratia,
Shigella, H. influenzae, N.
meningitidis)
Other: Chlamydia trachomatis,
Nocardia asteroides.
TRIMETHOPRIM is a dihydrofolate reductase inhibitor, which is available as a
single agent and in combination with sulfamethoxazole (trimethoprim 80 mg;
sulfamethoxazole 400 mg).
Clinical use:
-urinary tract infections
-respiratory tract infections (acute bronchitis)
-gastrointestinal infections (typhoid fever, diarrhea cased by ETEC)
-gonorrhea, brucellosis, periodontal infections, nocardiosis.
-Pneumocystis carinii infections
ANTIVIRAL DRUGS
ACYCLOVIR
VALACICYCLOVIR
FAMCICLOVIR
FOSCARNET
RIBAVIRIN
LAMIVUDINE
AMANTADINE
RIMANTADINE
INTERFERON ALFA
SYSTEMIC ANTIFUNGAL AGENTS
DRUG
DOSE
Polyenes
-Amphotericin B
1mg/kg (T=2-2,5g)
Flucytosine
150 mg/kg/d (in 4 doses)
Imidazoles
-Ketoconazole
-Itraconazole
-Fluconazole
INDICATIONS
Deep mycosis: Candida spp,
Cryptococcus neoformans, Aspergillus,
hystoplasma, blastomyces
Cryptococcosis, candidiasis (renal, CNS,
eye), chromomycosis
400 mg/d qd(>400mg/d
if meningitis)
Chronic cutaneous candidiasis,
coccidioidomycosis, histoplasmosis,
blastomycosis
Candidiasis vaginitis
Deep mycosis
200 mg/d bid
200mgx3/d the first 3
days
Oropharyngeal candidiasis
50-100 mg once daily
Esophagial candidiasis
100-400 mg
Cryptococcal meningitis
400 mg/d-2 mo (after the
initial therapy with