Bacteremia and Antibiotic therapy 2018, Current Medical diagnosis and treatment, Dr. Omar Ansari, Specialist internal medicine

1. BACTEREMIA & ANTIBIOTIC
THERAPY
DR. Omar Ansari

2. Gram Staining
 The name comes from the
Danish bacteriologist Hans Christian Gram,
who developed the technique.
 Gram staining differentiates bacteria by the
chemical and physical properties of their cell
walls by detecting peptidoglycan, which is
present in the cell wall of Gram-positive bacteria
 Used crystal voilet to dye

3. What is meant by Gram +/- ?

6. GRAM NEGATIVES

7. Diseases caused by Gram -
 Whooping Cough
 Meningococcal meningitis
 Infections due to haemophillus
 Infections due to Moraxella catarahalis
 Typhoid fever
 Shigellosis
 Cholera
 Brucellosis
 Gonococcus infections

8. Gram negative bacteremia
 Most common sites:
1. Lungs
2. GU
3. GI
4. Hepato-biliary tract
 Less common sites:
1. IV lines
2. Surgical wounds
3. Drains
4. Pressure ulcers

9. Symptoms and signs
Fever and chill abruptly started.
15% may be hypothermic <36.4
5% may never develop more than
37.5

10. Symptoms and Signs
 Hyperventilation
 Respiratory alkalosis
 Changes in mental status
 Hypotension and shock occurs in 20-50% with
unfavorable prognostic signs.

11. Lab
 Neutropenia/Neutrophillia
 Thrombocytopenia in 50% of cases.
 Three blood culture from separate sites could
increase the organism detection to 95%.

12. Identifying the source of bacteremia
 By finding the source of infection such as
removing CVC or draining abscess a fatal
disease becomes easily treatable.

13. ABX
 No delay should be made after diagnosis is
suspected esp. if hypotension
develops.
 Gram positive bacteremia cannot be
distinguished from gram positive therefore
broad spectrum ABX should be
used.

14. GRAM POSITIVES

15. Gram positive infections
1. Streptococcal infection
2. Enterococcal infection
3. Pneumococcal infection
4. Staphyloccocal infections
5. Clostridial infection
Aerobic
Anaerobic

16. 1. Streptococcal infections
1. Group A:
a. Pharyngitis
b. Streptococcal skin infections (SSTI): Impteigo
and Erysipelas
TT: Cefazolin 1g TID or Vanco 1g BID
Amoxcillin 875 BID, Cephalexin 500mg
QID

17. Other Group A streptococcal infection
 Arthritis
 Pneumonia
 Endocarditis
 Necrotizing fasciitis
 Streptococcal toxic shock syndrome
Same treatment as Group A

18. 2. Pneumococcal infection
 Pneumococcal pneumonia
 Pneumococcal meningitis

19. 3. Enterococcal infections
2 species
• Enterococcus faecalis
• Enterococcus faecum
Infections:
• Wound infection
• UTI
• Bacteremia
• Endocarditis
Treatment:
Linezolid
Vanco

20. 4. Staphylococcal infections
1. SSTI
2. OM
3. Bacteremia

21. Staphylococcal Bacteremia
 S aureus readily invades the blood stream and
infects distant sites.
 Whenever S aureus is detected in blood culture
the possibility of endocarditis, osteomyelitis or
other metastatic deep infections must be
considered.

22. Empiric treatment of S. Aureus
 Methicillin sensitive SA (MSSA): Cefazolin 2g
TID or Naficillin 2g QID
 Methicillin resistant (MRSA): Vancomycin 15-
20mg/Kg/dose or Daptomycin 6mg /Kg
 Duration of treatment: 4-6 weeks
 In Uncomplicated cases: 14 days is enough

23. Toxic Shock Syndrome
 S. Aureus produces toxin and could cause TSS in adults.
 Characterized by :
1. High fever
2. Vomiting
3. Watery diarrhea
4. Sore throat
5. Myalgia
6. Headache
7. Hypotension with kidney and heart failure is associated with poor outcome
8. A diffuse macular erythematous rash and nonpururlent conjunctivitis
9. Desquamation of palm and soles during recovery
10. Usually after tampon use; nasopharynx, bone, vagina, rectum, abscess, or wound.
 Treatment:
1. Rapid rehydration
2. Antistaphyloccal drugs
3. Management of kidney or heart failure
4. Removal of tampon

24. ANAEROBIC INFECTIONS

25. Anaerobic infections
 ANAEROBIC Non spore formers:
1. Gram-negative rods :Bacteroides ,
Fusobacterium
2. Gram-positive rods : Actinomyces, Eubacterium
Bifidobacterium, Lactobacillus, Propionibacterium
3.Gram-positive cocci :Peptostreptococcus,
Peptococcus
4. Gram-negative cocci : Veillonella,
Acidominococcus
 ANAEROBIC SPORE – FORMERS: Gram-
positive rods Clostridium tetani Clostridium

26. General consideration
Anaerobic bacteria is majority NORMAL FLORA.
• Normal flora of mouth: Anaerobic spirochetes, fusobacteria
• Skin: Anaerobic diphteroids
• Large bowel: Bacteroids
• Female gentalia
These normal produces disease when displaced from their normal sites.
Anaerobic infections are polymicrobial and abscessess are common.
Septic thrombophelebitis and metastic infections are common.
Cultures are negative mostly if not collected under anaerobic conditions.

27. Head & Neck Anaerobic
infections
 Causes: Chronic sinusitis, COM, Peritonsillar
abscess, Mastoditis.
 Treatment:
1. Inj. Ampicillin Sulbactam 1.5-3g QID
2. Amoxicillin/clavulanic acid 875/125 mg BID
3. Clindamycin 300mg QID

28. Chest Anaerobic infection
 Aspiration of saliva ( contains 10,000,000,00 anaerobic organisms per
mL in addition to aerobic)
 Poor oral hygeine
 Periodontal disease
Causes:
1. Necrotizing Pneumonia
2. Lung abscess
3. Empyema
Treatment:
1. Chest tube or surgical drainage of empyema
2. Clindamycin injection 600 mg IV once followed by 300mg TID
3. Ceftriaxone 1g daily
4. Moxifloxacin 400mg IV or oral
5. Duration (4-6 weeks)

29. Intra-abdominal anaerobic infectinos
 In Colon ( 100,000,000,000 anaerobes per gram)
Organism:
1. B Fragilis
2. Clostridia
3. Peptostreptococcus
Causes:
1. Trauma to colon
2. Inflammations (eg Appendicitis)
Is with gram negative rods or enteroccoci.

30. Treatment Intra abdominal
Community onset
1. B Fragilis : Flagyl, Moxifloxacin, Tigecycline,
Etrapenem, Imipenem, Piperacillin tazobactam,
doripenem, ceftolozane/tazobactam
1. Oral: Moxifloxacin 400mg OD
2. Moderate to severe: Ceftriaxone 1g OD or Cipro
400mg BID + Metro 500mg TID OR Etrapenem
1g OD
3. Severe infection: Meropenem 1g TID or
Impenem 500mg TID or QID

31. Health care associated
 Imipenem 500mg TID or QID
 Meropenem 1g TID
 Piperacillin 3.75 Qid
OR
 Cefepime or Ceftazidime 2g TID + Metro 500mg
TID

32. ANTIBIOTIC THERAPY

33. 1. PENCILLIN

34. Mechanism of action
Pencillins
Beta lactam ring
Pencillin binding receptors causes supression
of peptoglycan and autolysis of cell wall.

35. 4 types of Penicillin
1. Natural Pencillin: Pencillin G and V : Gram positive
2. Extended spectrum pencillins or aminopencillin
are Gram + and modest aerobic
Gram - activity
a. Amoxicillin
b. Ampicillin
c. Piperacillin tazobactam or Ticarcillin clavulanate:
Broad spectrum, Psuedomonas, Klebsilla, B Fraglis,
Serratia
Dose: 200-300mg/kg/day

36. 3. Penicillin's Combined with Beta-
Lactamase Inhibitors
 The addition of beta-lactamase inhibitors
(clavulanic acid, sulbactam, tazobactam)
prevents inactivation of the parent penicillin by
some, but not all, bacterial beta-lactamases.
 In general, the beta-lactamase inhibitors
effectively inactivate beta-lactamases produced
by Staphylococcus aureus, H influenzae,
Moraxella catarrhalis, and B fragilis.

37. 4. Antistaphyloccocal Pencillins
 Oxacillin, cloxacillin, dicloxacillin, and nafcillin
 They have been found to be superior to
vancomycin in methicillin-susceptible S aureus.
 They are less active than natural penicillins
against nonstaphylococcal gram-positive
bacteria;
 however, they are still effective in the treatment of
certain streptococcal infections, including skin
and soft tissue infections due to group A
streptococci.

38. Pencillins adverse effects
 Anaphylaxis
 Seizure
 Diarrhea: Augmentin
 Hypokalemia : Pipracillin
 An increased rate of nephrotoxicity has been
observed with the combination of piperacillin-
tazobactam and vancomycin.
 Dicloxacillin may cause decreases in INR levels
in patients receiving warfarin.

39. CEPHALOSPORINS

40. CEPHALOSPORINS
 The cephalosporins, structurally related to the
penicillins, consist of a beta-lactam ring.
 Mechanism of action is same as PENCILLINS.
5 GENERATIONS
 1st Generation: aerobic gram-positive
organisms (but not enterococcus) and some
community-acquired gram-negative
organisms (P mirabilis, Escherichia coli,
Klebsiella species)

41. 5 Generations
2nd Generation:
 medications have a slightly extended spectrum against aerobic
gram-negative bacteria, and some are active against gram-
negative anaerobes (eg,cefoxitin)
3rd Generation
active against many aerobic gram-negative bacteria
4th Generation
 it is more stable against plasmid-mediated beta-lactamase
 improved coverage against Enterobacter and Citrobacter
species.
 The gram-positive coverage of cefepime approaches that of
cefotaxime.
 None of the currently available agents are active against the
enterococcus.

42.  A fifth-generation cephalosporin, ceftaroline, is
uniquely active against methicillin-resistant S
aureus and has comparable gram-negative
spectrum activity as cetriaxone.

43. Generation 1:
 Oral :Cephalexin, cephradine, and cefadroxil
 IV: Cefazoline
Gram positive Cocci and Gram negatives (E coli,
Klebsiella pneumoniae, and P mirabilis) and Anaerobes
but not B.Fragilis.
 Treatment of urinary tract infections and minor
skin and soft tissue infections (eg, cellulitis, soft
tissue abscess)
 IV Cefazoline : prophylaxis of infection of most clean
surgical procedures
 Limitation: No effect on MRSA

44. Generation 2:
 Heterogeneous group
 Oral: cefaclor, cefuroxime axetil, and cefprozil can be given orally
 More gram negative activity than G1: Proteus and Klebsiella
(including first-generation cephalosporin-resistant strains), Morexalla
Cataralis.
 They are less active than amoxicillin against Streptococcus
pneumoniae.
 Cefuroxime is active against H influenzae. absorption is enhanced
when it is taken with food (as is not the case with many other oral
antibiotics).
 IV Cefoxitin and cefotetan are active against anaerobes, including
many strains of B fragilis. But are resistant.
 Usage: cefprozil and cefuroxime axetil have a role in the treatment of
sinusitis and otitis media in those patients unresponsive to
amoxicillin.

45. Generation 3:
 Cefpodoxime proxetil, cefdinir, cefditoren pivoxil,
cefixime, and ceftibuten. (the only oral agents in this
group) are more active than cefuroxime axetil against
gram-negative pathogens).
 IV: Cefotaxime, Ceftraixone and Ceftazidime
 Ceftriaxone and cefotaxime are the most reliable
antipneumococcal coverage.
 Ceftazidime is unique among all third-generation
agents because it is active against P aeruginosa.
Ceftazidime, however, has notably weak activity
against S aureus and pneumococci.
 All are inactive against Enteroccoci.

46. Generation 4
 cefepime—the only fourthgeneration
 is more active against Enterobacter and
Citrobacter, has activity comparable to that of
ceftazidime against P aeruginosa, and has gram-
positive activity similar to that of ceftriaxone.
 treatment of multidrug-resistant P aeruginosa

47. 5th Generation
 activity against methicillin-resistant S aureus
 methicillin-resistant S aureus , The only CS
 Ceftazidime or cefepime is frequently
administered empirically in the febrile neutropenic
patient.
 two cephalosporin-beta-lactamase inhibitor
combinations are available, ceftazidime-
avibactam and ceftrolozane-tazobactam

48. Adverse effect
 The frequency of IgE cross-allergy between
cephalosporins and penicillins approximates 5–
10%.
 Cefriaxone has been associated with a dose-
dependent biliary sludging syndrome and
cholelithiasis due to precipitation of medication
when its solubility in bile is exceeded. Long-term
administration of 2 g/day or more is a risk factor
for this complication.
 Cefepime may be associated with an increased
rate of neurotoxicity, particularly with large doses
and concomitant kidney disease.

49. AMINOGLYCOSIDES

50. Medications
 streptomycin,neomycin, kanamycin, amikacin, ge
ntamicin, tobramycin, sisomicin,
netilmicin,paromomycin, and spectinomycin.
 All these agents inhibit protein synthesis in
bacteria
 They are most commonly used in combination
with other agents to treat resistant gram-
negative organisms.
 Although aminoglycosides demonstrate in vitro
activity against many gram-positive bacteria, they
should never be used alone to treat infections
caused by these organisms.

51. Adverse effect
 All aminoglycosides can
cause ototoxicity and nephrotoxicity.
 Ototoxicity is more likely to be irreversible,
presenting as hearing loss (cochlear damage), noted
first with high-frequency tones, or as vestibular
damage, manifested by vertigo.
 Amikacinis likely more cochlear-toxic.
 Nephrotoxicity is usually reversible.
 In very high doses, usually associated with irrigation
of an inflamed peritoneum, aminoglycosides can
be neurotoxic, producing a curare-like effect with
reversible neuromuscular blockade that results in

52. Metronidazole/Tinidazole

53. METRONIDZOLE
 Metronidazole is an antiprotozoal medication also active against
most anaerobic gram-negative bacilli (ie, Bacteroides,
Prevotella, Fusobacterium) as well as Clostridium species but
has minimal activity against many anaerobic gram-positive and
microaerophilic organisms.
 The medication is metabolized in the liver, and dosage reduction
is required in severe hepatic insufficiency or biliary dysfunction.
 In contrast to clindamycin or cefoxitin and
cefotetan, metronidazole is active against virtually all B
fragilis isolates.
 Metronidazole is less expensive and equally as efficacious as
oral vancomycin for the therapy of mild C difficile colitis.
 Adverse effects include stomatitis, nausea, and diarrhea
 With prolonged use at high doses, reversible peripheral
neuropathy can develop
 Metronidazole can decrease the metabolism of warfarin,
necessitating dosage adjustment of warfarin.

54. VANCOMYCIN

55. VANCOMYCIN
 Vancomycin is bactericidal for most gram-positive
organisms, particularly staphylococci and
streptococci; it is, however, bacteriostatic for most
enterococci.
 Vancomycin kills more slowly when compared with
nafcillin or cefazolin, and these agents are preferred
in the treatment of serious infection associated with
methicillin-resistant S aureus.
 vancomycin-resistant strains of enterococci
(particularly E faecium) are common.
 S aureus both intermediately sensitive and highly
vancomycin-resistant has been observed in patients
receiving long-term vancomycin therapy

56. Indication
 (1) Severe staphylococcal infections in patients
with type 1 allergy to penicillin. (2) Methicillin-
resistant S aureus and methicillin-resistant S
epidermidis infections. (3) Serious infections
(pneumonia, meningitis) due to resistant S
pneumoniae. (4) Severe enterococcal infections.
(5) Other gram-positive infections in penicillin-
allergic patients, eg, viridans streptococcal
endocarditis. (6) Surgical prophylaxis in penicillin-
allergic patients in clean surgical procedures. (7) For
gram-positive infections due to organisms that are
multidrug-resistant, ie, Corynebacterium jeikeium. (8)
Endocarditis prophylaxis in the penicillin-allergic
patient.

57. Oral Vancomycin
 Severe C. difficle 0.125g four times daily
effective than Metro.

58. Adverse effects
 Thrombophelibitis – Site of infection
 Some studies suggest vancomycin doses (equal
or greater than 4 g daily) and elevated trough
levels are associated with an increased incidence
of mild nephrotoxicity.
 Rapid infusion or high doses (1 g or more) may
induce diffuse hyperemia (“red man syndrome”)
and can be avoided by extending infusions over
1–2 hours, by reducing the dose, or by
pretreating with a histamine antagonist such as
hydroxyzine.

59. QUINOLONES

60. Mode of action
 The mode of action of all quinolones involves inhibition of bacterial DNA
synthesis.
 excellent activity against Enterobacteriaceae but are also active
against other gram-negative bacteria such as Haemophilus, Neisseria,
Moraxella, Brucella, Legionella, Salmonella, Shigella, Campylobacter,
Yersinia, Vibrio, and Aeromonas organisms.
 In general, the fluoroquinolones are less potent against gram-positive
than against gram-negative organisms. The exception is delafloxacin,
which shows enhanced activity against gram-positive organisms.
 BUT Gemifloxacin, levofloxacin, and moxifloxacin also have excellent
gram-positive activity, including against streptococci, pneumococci
and S aureus and S epidermidis,
 Moxifloxacin and delafloxacin demonstrate modest activity against many
of the significant anaerobic pathogens, including B fragilis and
mouth anaerobes, but only moxifloxacin is approved for the treatment
of intra-abdominal infection. Moxifloxacin also provides the most reliable
coverage of M tuberculosis.

61. Quinolones
 Fluoroquinolones bind some heavy metals; thus,
absorption is inhibited when administered concomitantly
with iron, calcium. Optimal oral bioavailability is achieved if
fluoroquinolones are taken 1 hour before or 2 hours after
meals.
 Indications:
1. Uncomplicated UTI
2. CAP (Respiratory FQ,
gemifloxacin, levofloxacin, moxifloxacin)
3. Because quinolones have excellent penetration into
prostatic secretions, they are effective in treating both
acute and chronic bacterial prostatitis associated with
susceptible pathogens.
4. SSTI
5. OM
6. OE

62. Adverse effect
 Prominent: nausea, vomiting, and diarrhea
 headache, dizziness, seizures, insomnia, impaired
liver function, and skin rashes
 hypoglycemia (especially with gatifloxacin, which has
been removed from the US market, and moxifloxacin)
 Except for delafloxacin, fluoroquinolones prolong the
QT interval
 Quinolones should be used cautiously in patients
receiving antiarrhythmics such as amiodarone or in
persons with a history of prolonged QT
 Prolongation of the prothrombin time and the
international normalized ratio

63. Tendinitis and tendon rupture
 Tendinitis and tendon rupture have been reported with
quinolone agents.
 The proposed mechanisms for this adverse event are not
completely understood. It is known that fluoroquinolones
decrease type I collagen, elastin, fibronectin, and beta-1-
integrin and inhibit cell proliferation and synthesis of matrix
ground substance (fibroblast metabolism). However, the
true mechanism for this complication is unclear.
 Nonetheless, risk factors are well known and include
concomitant corticosteroid use and age older than 60
years.
 Patients experiencing musculoskeletal symptoms while
receiving fluoroquinolones should discontinue therapy
 the FDA has issued warnings regarding peripheral
neuropathy. Its onset can be within a few days of initiation
of therapy and can be permanent in some patients. Lastly,
while rare, fluoroquinolones are associated with an
increased rate of aortic aneurysm and dissection.