no descriptions

1. INFECTIOUS
DISEASES
PHARMACOTHERAP
Y
Kassahun Bogale
Assistant Professor of Clinical Pharmacy
1

2. Principles of antimicrobial
regimen selection

3. Introduction
3
 Antimicrobials are among the most widely
used classes of drugs
 Approximately 20% to 40% of hospitalized
patients receive antibiotics.
 The use of antibiotics is the main driver in
creating selective pressure for the emergence
of antimicrobial resistant pathogens;
nevertheless, antibiotic overuse remains
common

4. Common Terms
 AUC (area under the time versus concentration
curve):
 the body's total exposure to a drug, as a function of the
amount of drug that enters the systemic circulation and
clearance.
 MIC (minimum inhibitory concentration):
 an in vitro test which determines the lowest
antimicrobial concentration that prevents visible growth
of an organism after approximately 24 hours of
incubation in a specified growth medium.
 MBC (minimum bactericidal concentration):
 an in vitro test which determines the lowest
4

5. Common Terms
 Bactericidal:
 antibiotics that have a similar MIC and MBC.
 For drugs that are bactericidal, antibacterial
outcome generally is associated with killing as
opposed to inhibition of growth.
 Bacteriostatic:
 antibiotics that have an MIC lower than the MBC.
 The antibacterial effect of these drugs is inhibition
of growth as opposed to killing.
5

6. Common Terms
 Pharmacokinetics:
 describe the absorption, distribution,
metabolism and elimination of a drug.
 E.g. AUC, Cmax (peak blood level), Cmin
(trough blood level), t1/2 (half-life), and Vd
(volume of distribution).
6

7. Common Terms
 Pharmacodynamics:
 the relationship between drug concentration and
its effect.
 MIC is an example of a pharmacodynamic
parameter.
 Post antibiotic effect:
 the persistence of antimicrobial activity after
removal of a drug or after levels drop below
MIC.
7

8. Time-dependent killing
 Bacterial eradication (drug efficacy)
 dependent on the amount of time (percentage of
the dosing interval) that blood levels of antibiotic
exceed the MIC for the pathogen
 referred to as t>MIC, or the amount of time that the
pathogen is exposed to drug.
 Examples of drugs that exhibit time-dependent
killing
 beta-lactams, glycopeptides, and macrolides.
 Usually, t>MIC must be at least 40% to 50%
 Continuous IV infusion (beneficial)
8

9. Concentration-dependent killing
 Bacterial eradication (drug efficacy) is related to
 Cmax/MIC and AUC/MIC ratios, or
 increased effect with increased blood levels of drug.
 Examples:
 Aminoglycosides and fluoroquinolones.
 Preferred AUC/MIC ratio: >100
9

10. Concentration-dependent killing
 Cmax/MIC ratio
 Aminoglycosides: 10 to 12
 Fluoroquinolones: 25 to 35
 Extended-interval dosing is preferable for these
types of drugs (high peaks are good)
 The total amount of drug administered
determines efficacy.
10

11. Rule of Thumb
Drug dose primarily affects the
Cmax/MIC and AUC/MIC ratios.
Dosing interval primarily affects the
AUC/MIC ratio and t>MIC.
Infusion time primarily affects t>MIC.
11

12. Systematic Approach for
Selection of Antimicrobials
 Choosing an antimicrobial agent to treat
an infection is far more complicated than
matching a drug to a known or suspected
pathogen.
 Following a systematic approach to select
an antimicrobial regimen is essential
 Problems arise when this systematic
approach is replaced by prescribing
broad-spectrum therapy to cover as many
organisms as possible.
12

13.  Consequences of not using the systematic
approach include
 the use of more expensive and potentially more
toxic agents, which can, in turn, lead to
widespread resistance and difficult-to-treat
super-infections.
 Another abuse of antimicrobial agents is
administration when they are not needed
such as when they are prescribed for self-
limited clinical conditions that are most
likely viral in origin (i.e., the common cold).
13

14. Systematic Approach for Selection of
Antimicrobials
Empirical (patient's history and P.E and results of Gram stains
from the infected site).
Confirm the presence of infection
• Careful history and physical; Signs and symptoms;
Predisposing factors
Identification of the pathogen
• Collection of infected material; Stains; Serologies; Culture and
sensitivity
Selection of presumptive therapy considering infected
site
• Host factors; Drug factors
Monitor therapeutic response
14

15. Empirical Therapy
 Initial selection of antimicrobial therapy is
nearly always empirical, which is prior to
documentation and identification of the
offending organism.
 Infectious diseases generally are acute,
and a delay in antimicrobial therapy can
result in serious morbidity or even
mortality.
15

16.  Empirical antimicrobial therapy selection
should be based on information gathered from
 the patient's history and physical examination
 results of Gram stains or of rapidly performed
tests on specimens from the infected site.
 This information, combined with knowledge of
the most likely offending organism(s) and an
institution's local susceptibility patterns, should
result in a rational selection of antibiotics to
treat the patient.
16

17. Confirming The Presence Of
Infection
 Fever is the hallmark of infectious diseases:
 body temperature > 37°C (98.6°F)
 Body T° is controlled by hypothalamus.
 In addition, the circadian rhythm, a built-in
temperature cycle, is also operational.
 In a healthy person, the internal thermostat is set
between the morning low temperature and the
afternoon peak as controlled by the circadian
rhythm.
 During fever, the hypothalamus is reset at a
higher temperature level.
 Normal body temperature taken orally is:
17

18. Does fever means infection at all
times?
 "false-positives"
 Collagen-vascular (autoimmune) disorders;
malignancies; fever of unknown or undetermined
origin
 Drugs - 5% of drug reactions
 Beta-lactam antibiotics, anticonvulsants, allopurinol,
hydralazine, nitrofurantoin, sulfonamides,
phenothiazines, and methyldopa
 False-negative
 The absence of fever in a patient with signs and
symptoms consistent with an infectious disease.
 Masking fever: aspirin, acetaminophen, non-
steroidal anti-inflammatory agents, and
18

19.  The use of antipyretics should be discouraged
during the treatment of infection unless
absolutely necessary because they can mask
a poor therapeutic response.
 Moreover, elevated body temperature, unless
very high (>40.5°C ), is not harmful and may
be beneficial.
19

20. WBC count
 Most infections cause leukocytosis
 Normal values: 4,000 - 10,000 cells/mm3
 Bacterial infections:
 Granulocyte counts, often with immature forms (band
neutrophils)
 The presence of immature forms (left shift) is an
indication of an increased bone marrow response to
the infection.
 low leukocyte counts after the onset of infection
indicate an abnormal response and generally are
associated with a poor prognosis.
 With infection, peripheral WBC counts can be very
high, but they are rarely higher than 30,000 to
40,000 cells/mm3.
20

21. WBC count
 Lymphocytosis, even with normal or slightly
elevated total WBC counts, may indicate
 Tuberculosis, viral or fungal infections.
 Increases in monocytes may indicate
 Tuberculosis or lymphoma
 Elevation of eosinophils
 Allergic reactions to drugs or infections caused
by metazoa
 Many types of infections can be accompanied
by a completely normal WBC count and
differential.
21

22. Local Signs
 Pain and inflammation can be manifested as
 Swelling, erythema, tenderness, and purulent
drainage. (only visible if the infection is superficial)
 The manifestations of inflammation in deep-
seated infections (e.g., meningitis, pneumonia,
endocarditis, and urinary tract infection) must be
ascertained by examining tissues or fluids.
For example: During bacterial infection of:
 CNS infection: Neutrophils in spinal fluid
 UTI: pyuria
 Pyelonephritis: flank pain and dysuria
 Pulmonary infection: cough and sputum production
22

23. Identification of the Pathogen
 Gram stain might reveal bacteria, or an acid-
fast stain might detect mycobacteria or
actinomycetes.
 Infected body materials must be sampled
before institution of any antimicrobial therapy
 Ideally, blood should be obtained from
peripheral sites as two sets (one set consists
of an aerobic bottle and one set an anaerobic
bottle) from two different sites approximately 1
hour apart.
23

24. Interpreting culture Results
24
 After a positive Gram stain, culture results, or both
are obtained, the clinician must be cautious in
determining whether the organism recovered is a
true pathogen, a contaminant, or a part of the
normal flora.
 The latter consideration is especially problematic
with cultures obtained from the skin, oropharynx,
nose, ears, eyes, throat, and perineum.
 These surfaces are heavily colonized with a wide
variety of bacteria, some of which can be
pathogenic in certain settings. For example,
coagulase-negative staphylococci are found in
cultures of all the aforementioned sites, yet are
seldom regarded as pathogens unless recovered
from blood, venous access catheters, or prosthetic

25. Selection of Presumptive
Therapy
 Drugs of choice are compiled from a variety of
sources and are intended as guidelines rather
than as specific rules for antimicrobial use.
 These choices are influenced by local
antimicrobial susceptibility data rather than
information published by other institutions or
national compilations.
 Hence, each institutions should publish an
annual summary of antibiotic susceptibilities
(antibiogram) for organisms cultured from
patients to guide empirical antibiotic therapy
25

26. 26
 Susceptibility of bacteria can differ
substantially among hospitals within a
community.
 For example, the prevalence of hospital-
acquired methicillin-resistant Staphylococcus
aureus (HAMRSA) in some centers is quite
high, whereas in other centers the problem
might be nonexistent.
 This particular situation will influence the
selection of therapy for possible S. aureus
infection, where the clinician must choose

27. 27
 Empirical therapy is directed at organisms that
are known to cause the infection in question.
 To define the most likely infecting organisms, a
careful history and physical examination must be
performed.
 The place where the infection was acquired
should be determined, for example, the home
(community acquired), nursing home environment,
or hospital acquired (nosocomial).
 Hospitalized and nursing home patients can be
exposed to potentially more resistant organisms
because they are often surrounded by ill patients
who are receiving antibiotics.

28. Host factors
28
Allergy
 Allergy to antimicrobials generally precludes
its use.
 E.g allergic reactions to Penicillin & penicillin-
related compounds
 Use cephalosporins or carbapenems to patients
allergic to penicillin under close supervision in
patients with a history of delayed reactions, such
as a rash but not for patients who have a history
for immediate or accelerated reactions (e.g.,
anaphylaxis, laryngospasm)
 Use Monobactams only for gram negative

29. Host Factors …
Age:
 The patient’s age is an important factor both in trying to
identify the likely etiologic agent and in assessing the
patient’s ability to eliminate the drug(s) to be used.
 The best example of an age determinant of organisms
is in bacterial meningitis, where the pathogens differ
as the patient grows from the neonatal period through
infancy and childhood into adulthood.
 For neonates, hepatic and liver functions are not well
developed. Therefore, bilirubin excretion is decreased
resulting in increased concentration of unconjugated
bilirubin that can cause kernicterus.
 Kernicterus: sulfonamides
 Chloramphenicol (gray baby syndrome in newborn)
 Renal toxicity: aminoglycosides (>65 yrs)
29

30. 30
Pregnancy:
 During pregnancy, not only is the fetus at risk for
drug teratogenicity, but also the pharmacokinetic
disposition of certain drugs can be altered.
 E.g. Penicillins, cephalosporins, and aminoglycosides
(up to 50%) are cleared from the peripheral circulation
more rapidly during late pregnancy
 This is probably a result of marked increases
in intravascular volume, glomerular filtration
rate, and hepatic and metabolic activities.

31. Host Factors…
Genetic variation:
 E.g. slow acetylators of isoniazid are at
greater risk for peripheral neuropathy.
 Patients with severe deficiency of glucose-6-
phosphate dehydrogenase can develop
significant hemolysis when exposed to such
drugs as sulfonamides, nitrofurantoin, nalidixic
acid, antimalarials, dapsone, and
chloramphenicol.
 HIV Patients with a human leukocyte antigen
allele HLA-B*5701positive are associated with
a severe hypersensitivity reaction to Abacavir
31

32. Host Factors…
Organ Dysfunction
 Patients with diminished renal or hepatic function
or both will accumulate certain drugs unless the
dosage is adjusted.
 Recommendations for dosing antibiotics in patients
with liver dysfunction are not as formalized as
guidelines for patients with renal dysfunction.
Any concomitant therapy:
 E.g. Co-administration of isoniazid and
phenytoin can result in phenytoin toxicity
secondary to inhibition of phenytoin metabolism by
isoniazid.
32

33. Drug Factors
 Aminoglycosides
 concentration-dependent effect
 high-dose, once-daily aminoglycosides
 Postantibiotic
 Aminoglycosides, clindamycin, macrolides,and
tetracyclines
 Concentration-dependent killing
 Fluoroquinolones
33

34. Drug Factors…
 Beta-Lactams:
 time-dependent bactericidal effects (T > MIC)
 Effective dosing regimens require serum drug
concentrations to exceed the MIC for at least
40% to 50% of the dosing interval
 Frequent small doses or a continuous infusion
34

35. DRUG TOXICITY
 CNS Toxicities
 Penicillins, Cephalosporins, Quinolones, and
Imipenem cause CNS toxicity if dose adjustment
is not done during renal impairment
 Hematologic Toxicities: (with prolonged use)
 Nafcillin (Neutropenia)
 Piperacillin (Platelet Dysfunction)
 Cefotetan (Hypoprothrombinemia)
 Chloramphenicol (Bone Marrow Suppression)
 Both Idiosyncratic and Dose-related Toxicity)
 Trimethoprim (Megaloblastic Anemia)
35

36. DRUG TOXICITY
 Reversible nephrotoxicity:
 Aminoglycosides and vancomycin.
 Reversible ototoxicity:
 Aminoglycosides or erythromycin.
 Photosensitivity:
 Azithromycin, quinolones, tetracyclines,
pyrazinamide, sulfamethoxazole, and trimethoprim.
 Clostridium difficile associated diarrhea and
colitis from all antibiotics
 Isoniazid prophylactically in older persons
 >45 years of age (increased hepatotoxicity with
age)
36

37. Cost
 Storage, preparation, distribution, and
administration, monitoring
 Many oral antimicrobials have been approved,
including cephalosporins, linezolid, and
fluoroquinolones, which can be used in place of
more expensive parenteral therapy
 Convenient once-a-day expensive agents
versus multiple-dose inexpensive agents arises.
37

38. Combination Antimicrobial
Therapy
Broadening the Spectrum of Coverage
 Intra-abdominal and female pelvic infections/mixed
infections of aerobic gram –ve and anerobic bacteria/
 Aminoglycoside + metronidazole or clindamycin
Synergism:
 Aminoglycosides + beta-lactams (P. aeruginosa and
Enterococcus)
 Penicillin + streptomycin/gentamicin
 Enterococcal Endocarditis
Preventing Resistance:
 The use of combinations to prevent the emergence of
resistance is applied widely but not often realized.
 The only circumstance where this has been clearly
effective is in the treatment of tuberculosis.
38

39. Monitoring Therapeutic
Response
 Change therapy according to Culture and
sensitivity reports
 Use of agents with the narrowest spectrum of
activity against identified pathogens is
recommended.
 WBC count and temperature should normalize
 Physical complaints: such as pain, shortness of
breath, cough, or sputum production should
diminish
 Appetite should be improved
 Radiologic improvement may lag behind clinical
improvement
 Antimicrobials serum concentration monitoring
39

40. Monitoring Therapeutic
Response….
 Switching the route of administration: Criteria
1. overall clinical improvement,
2. lack of fever for 8 to 24 hours,
3. decreased WBC count, and
4. a functioning gastrointestinal tract
 Drugs that exhibit excellent oral bioavailability
when compared with IV formulations include
ciprofloxacin, clindamycin, doxycycline,
levofloxacin, metronidazole, moxifloxacin, and
cotrimoxazole.
40

41. Failure of Antimicrobial Therapy
 Lack of response over 2 to 3 days
 nonbacterial in origin, undetected pathogen
 the host, or the pathogen.
Failure caused by Drug factors
 Drug interaction
 E.g. complexation of fluoroquinolones with
multivalent cations
 Laboratory error
 Failure due to drug selection:
 Malabsorption (short-bowel syndrome)
41

42.  Accelerated drug clearance during Cystic
fibrosis or during pregnancy
 E.g. aminoglycosides
 Poor Penetration of antibiotics in to site of
action
 CNS, eye, and prostate gland
Failure caused by host factors:
 Immunosuppressed (e.g., neutropenia from
chemotherapy or AIDS) respond poorly to
therapy
 Need of surgical drainage of abscesses or
removal of foreign bodies, necrotic tissue
42

43. 43
Failures Caused by Microorganisms
 There are two types of resistance, intrinsic and
acquired resistance.
 Intrinsic resistance is when the antimicrobial
agent never had activity against the bacterial
species. For example, gram-negative bacteria are
naturally resistant to vancomycin because the
drug cannot penetrate the outer membrane of
gram-negative bacteria.
 Acquired resistance is when the antimicrobial
agent was originally active against the bacterial
species but the genetic makeup of the bacteria
has changed so the drug can no longer be

44.  Primary resistance
 enterococci, pneumococci, and Mycobacterium
tuberculosis.
 Enterococci have been isolated with multiple resistance
patterns.
 Beta-lactams
 by virtue of beta-lactamase production, altered
penicillin-binding proteins [PBPs], or both
 Vancomycin
 via alterations in peptidoglycan synthesis
 High levels of aminoglycosides
44

45.  Pneumococci resistant to penicillins, certain
cephalosporins, and macrolides are common
 Causes:
 overgrow; Overuse; immunosuppressed patients; long-term
suppressive antimicrobials
 P. aeruginosa:
 Resistance developed during antimicrobial therapy
(20% to 30%)
 Beta-lactamase producing organisms:
 Enteric gram-negative bacilli (P. aeruginosa,
Enterobacter aerogenes, Enterobacter cloacae,
Citrobacter freundii, Serratia marcescens, and a few
others)
45

46. Classification
Gram-positive Cocci
 Enterococcus faecalis:
 generally not as resistant to antibiotics as
Enterococcus faecium
 E. faecium:
 generally more resistant to antibiotics than E.
faecalis
 Staphylococcus aureus/Staphylococcus
epidermidis
 Methicillin (oxacillin)-sensitive or Methicillin
(oxacillin)–resistant
46

47. Gram-positive Cocci…
 Streptococcus:
 groups A, B, C, G, and Streptococcus bovis
 Streptococcus pneumonia:
 Penicillin-sensitive ; Penicillin intermediate or
Penicillin resistant
 Streptococcus viridans group
47

48.  GRAM-NEGATIVE COCCI
 Moraxella (Branhamella) catarrhalis
 Neisseria gonorrhoeae (also give concomitant
treatment for Chlamydia trachomatis
 Neisseria meningitides
 GRAM-POSITIVE BACILLI
 Clostridium perfringens
 Clostridium difficile
48

49. Gram-Negative Bacilli
 Acinetobacter spp.
 Enterobacter spp.
 Escherichia coli
 Haemophilus
influenzae
 Klebsiella
pneumoniae
 Legionella spp.
 Pasteurella multocida
 Proteus mirabilis
 Proteus (indole-positive)
(including Providencia
rettgeri, Morganella
morganii, and Proteus
vulgaris )
 Providencia stuartii
 Pseudomonas aeruginosa
 Salmonella typhi
 Serratia marcescens
49

50.  Miscellaneous Microorganisms
 Chlamydia pneumoniae
 C. trachomatis
 Mycoplasma pneumoniae
 SPIROCHETES
 Treponema pallidum
 Borrelia burgdorferi
50

51. Antimicrobial Use Management
Gram-Positive Cocci
Enterococcus faecalis
 Serious infection (endocarditis, meningitis,
pyelonephritis with bacteremia)
 Ampicillin (or penicillin G) + (gentamicin or
streptomycin)
 Vancomycin + ( gentamicin or streptomycin )
 linezolid, daptomycin, tigecycline
 Urinary tract infection (UTI)
 Ampicillin, amoxicillin
 Fosfomycin or nitrofurantoin
51

52. Antimicrobial Use Management
Gram-Positive
 E. faecium
 MORE resistant to antibiotics than E. faecalis
 Linezolid, quinupristin/dalfopristin, daptomycin,
tigecycline
 Staphylococcus Aureus/Staphylococcus
Epidermidis
 Methicillin (oxacillin)-sensitive
 Nafcillin or oxacillin
 FGC, trimethoprim-sulfamethoxazole, clindamycin,
BL/BLI
52

53. Antimicrobial Use Management
Gram-Positive cocci
Methicillin (oxacillin) resistant
Vancomycin ± (gentamicin or rifampin)
Linezolid, quinupristin-dalfopristin,
daptomycin, or tigecycline
Trimethoprim-sulfamethoxazole
53

54. Antimicrobial Use Management
Gram-Positive cocci
 Streptococcus
(groups A, B, C, G, and Streptococcus bovis)
 Penicillin G or V or ampicillin
 FGC
 Erythromycin, azithromycin, clarithromycin
54

55. Antimicrobial Use Management
Gram-Positive cocci
Streptococcus pneumoniae
 Penicillin-sensitive (MIC <0.1 mcg/mL)
 Penicillin G or V or ampicillin
 FGC, Erythromycin, azithromycin, clarithromycin
 Penicillin intermediate (MIC 0.1–1.0 mcg/mL)
 High-dose penicillin (12 million units/day for
adults) or ceftriaxone or cefotaxime
 Levofloxacin, moxifloxacin, gemifloxacin, or
vancomycin
55

56. Antimicrobial Use Management
Gram-Positive cocci
 Penicillin-resistant (MIC >1.0 mcg/mL)
 Vancomycin ± rifampin
Per sensitivities:
 TGC, levofloxacin, moxifloxacin, or gemifloxacin
56

57. Antimicrobial Use Management
Gram-Positive cocci
 Streptococcus, viridans group
 Penicillin G ± gentamicin
 TGC
 erythromycin, azithromycin, clarithromycin, or
 vancomycin ± gentamicin
57

58. Gram-Negative Cocci
 Moraxella (Branhamella) catarrhalis
 Amoxicillin-clavulanate, ampicillin-sulbactam
 Trimethoprim-sulfamethoxazole,
 erythromycin, azithromycin, clarithromycin,
 doxycycline
58

59. Gram-Negative Cocci
Neisseria Gonorrhoeae
 Also give concomitant treatment for Chlamydia
trachomatis
 Disseminated gonococcal infection
 Ceftriaxone or cefotaxime
 Oral follow-up:
 Cefpodoxime, ciprofloxacin, or levofloxacin
 Uncomplicated infection
 Ceftriaxone or cefotaxime, or cefpodoxime
 Ciprofloxacin or levofloxacin
Neisseria meningitides
 Penicillin G or TGC
59

60. Gram-Positive Bacilli
 Clostridium perfringens
 Penicillin G ± clindamycin
 Metronidazole, clindamycin,
 Doxycycline,
 Cefazolin
 Imipenem, meropenem, or ertapenem
 Clostridium difficile
 Oral metronidazole
 Oral vancomycin
60

61. Gram-Negative Bacilli
 Acinetobacter spp.
 Imipenem or meropenem ± aminoglycoside
(amikacin usually most effective)
 Ampicillin-sulbactam,
 Colistin or tigecycline
 Bacteroides fragilis (and others)
 Metronidazole, clindamycin,
 BLIC, cephamycins, or carbapenem
61

62. Gram-Negative Bacilli
 Enterobacter spp.
 Imipenem, meropenem, ertapenem, or
cefepime ± aminoglycoside
 Ciprofloxacin, levofloxacin, piperacillin-
tazobactam, ticarcillin-clavulanate, or
62

63. Escherichia Coli
 Meningitis
 TGC or meropenem
 Systemic infection
 TGC, Ampicillin-sulbactam
 fluoroquinolone,
 imipenem, meropenem
 Urinary tract infection
 Ampicillin, amoxicillin-clavulanate, doxycyline, or
cephalexin
 Aminoglycoside, FGC, nitrofurantoin,
fluoroquinolone
63

64. Gram Negative Organisms
Haemophilus influenzae
 Meningitis
 Cefotaxime or ceftriaxone
 Meropenem
 Other infections
 BLIC
 if beta-lactamase-negative - ampicillin or
amoxicillin
 Trimethoprim-sulfamethoxazole, cefuroxime,
 azithromycin, clarithromycin, or fluoroquinolone
64

65. Gram Negative Organisms
 Klebsiella pneumoniae
 TGC (if UTI only: aminoglycoside)
 Cefuroxime, fluoroquinolone, BLIC, imipenem,
meropenem,
 Legionella spp.
 Erythromycin ± rifampin or fluoroquinolone
 Trimethoprim-sulfamethoxazole,
clarithromycin, azithromycin, or doxycycline
65

66. Gram Negative Organisms
 Proteus mirabilis
 Ampicillin
 Trimethoprim-sulfamethoxazole, most antibiotics
except PRP
 Proteus (indole-positive) (including
Providencia rettgeri, Morganella morganii, and
Proteus vulgaris )
 TGC or fluoroquinolone
 BLIC, aztreonam, imipenem, or TGC PO
 Providencia stuartii
 TGC or fluoroquinolone
 Trimethoprim-sulfamethoxazole, aztreonam,
66

67. Gram Negative Organisms
 Pseudomonas aeruginosa
 cefepime, ceftazidime,
 piperacillin-tazobactam, or ticarcillin-clavulanate
plus aminoglycoside
 ciprofloxacin, levofloxacin, aztreonam,
 imipenem, meropenem
 UTI only:
 aminoglycoside
 Ciprofloxacin, levofloxacin
67

68. Gram Negative Organisms
 Salmonella typhi
 Ciprofloxacin, levofloxacin, ceftriaxone, or
cefotaxime
 Trimethoprim-sulfamethoxazole
 Serratia marcescens
 Piperacillin-tazobactam, ticarcillin-clavulanate, or
TGC ± gentamicin
 Trimethoprim-sulfamethoxazole,
ciprofloxacin levofloxacin, aztreonam, imipenem,
meropenem, or ertapenem
68

69. Miscellaneous Microorganisms
 Chlamydia pneumoniae
 Doxycycline
 Erythromycin, azithromycin, clarithromycin, or
fluoroquinolone
 Chlamydia trachomatis
 Doxycycline or azithromycin
 Levofloxacin or erythromycin
 Mycoplasma pneumoniae
 Erythromycin, azithromycin, clarithromycin or
fluoroquinolone
 Doxycycline
69

70. Spirochetes
Treponema pallidum
 Neurosyphilis
 Penicillin G
 Ceftriaxone
 Primary or secondary
 Benzathine penicillin G
 Doxycycline or ceftriaxone
70

71. Prevalence and antibiotic susceptibility
pattern of bacterial isolates from blood culture
in Tikur Anbassa Hospital, Addis Ababa,
Ethiopia.
Asrat D, Amanuel YW. Department of Medical Microbiology and
Parasitology, Faculty of Medicine, Addis Ababa University, P.O. Box 9086,
Addis Ababa.
 Between Mid-1996 and Mid-1998, 238 bacteria strains
isolated from blood culture of adult patients of Tikur
Anbassa Hospital, Addis Ababa, Ethiopia, were
retrospectively analyzed for their frequency of isolation
and antibiotic susceptibility pattern.
 Coagulase negative Staphylococcus aureus (CNS) were
isolated with the highest frequency 103 (43.3%), followed
by Staphylococcus aureus 34(14.3%)
 Klebsiella spp. 23(9.7%),
 E. Coli 19(8.1%),
 Pseudomonas spp. 16(6.7%),
 Acinetobacter spp. 12(5%),
71

72. Prevalence and antibiotic susceptibility pattern of
bacterial isolates from blood culture in Tikur Anbassa
Hospital, Addis Ababa, Ethiopia.
 The gram positive bacteria constituted 149(62.6%)
 Rates of susceptibility for
 gram positive range from 12% to 76%,
 gram negatives range from 8% to 46%.
 Among the gram positives, more than half of the isolates were sensitive to
 amoxicillin + clavulanic acid, ampicillin, carbenicillin,
 cephalothin, chloramphenicol,
 erythromycin and methicillin.
 Gram negative bacteria showed a high rate of resistance to many of the commonly
prescribed antimicrobial drugs:
 amoxicillin + clavulanic acid (65%), ampicillin (87.5%), amoxicillin (91.7%), carbenicillin
(75%),
 cephalothin (73.6%), chloramphenicol (65%),
 gentamicin (55.6%), kanamycin (54%),
 trimethoprim-sulphamethoxazole (64%) and tetracycline (61%).
 If generally considered, only gentamicin and kanamycin were relatively effective
against gram negatives.
 Over 85% Salmonella spp were sensitive to chloramphenicol and trimethoprim-
sulphamethoxazole.
72

73. The End!
73