This document discusses various types of antibiotic prophylaxis. It outlines recommendations for prophylaxis of infective endocarditis, which involves administering antibiotics prior to certain medical procedures for at-risk patients. It also mentions prophylactic preoperative antibiotics, prophylactic treatment for rheumatic fever, prevention of spontaneous bacterial peritonitis, meningitis prophylaxis, and prophylaxis for cellulitis. Common antibiotics used for different types of prophylaxis are listed, along with their dosages and administration routes. Mechanisms of antibiotic resistance in bacteria are summarized, including both intrinsic and acquired resistance.
3. Antibiotics Spectrum
Penicillin G : G+. Some G - as N. g, N.m.
Flucloxacillin: as pen G, but effective against β-
lactamase.
Ampcillin: G +, G –ve against many strains of H
influenzae, E. coli, S faecalis and Salmonella.
Antipseudomonal penicillins: piperacillin and
ticarcillin. G + variable and poor, useful against Gram –
(Pseudomonas) and many anaerobes.
Piperacillin/tazobactam: is empirical therapy in febrile
neutropenia (e.g., after chemotherapy (first line therapy).
4. Cephalosporins
1st : Cefazolin G+ and some G –ve.
2nd: Less G+, improved G - ve. cefuroxime can cross BBB.
3rd: reduced G+, improved G –ve. Only
Cefoperazone+sulb and Ceftazidime+Tazo. Effective
against P. aeuroginosa.
4th : Cefepime(Maxipime) similar to 3rd G; but, covers
pseudomonal infections.
5th : Ceftaroline cover MRSA
Ceftobiprole cover MRSA, Pencillin resistant S.
Pneumococci and enterococci.
5.
6.
7.
8. Monobactams and Carbapenem
Monobactams: against aerobic G -ve (alternative to
an aminoglycoside).
Carbapenem
Imipenem: G +, G – and anaerobes. β-lactamase
stable
Meropenem: is similar to imipenem
Doripenem: very similar to that of meropenem
Ertapenem: G +, G –ve and anaerobes. not MRSA,
ampicillin-resistant enterococci, P aeruginosa, or
Acinetobacter species.
9. Glycopeptides
Vancomycin: against aerobic and anaerobic G +ve
including MRSA
Teicoplanin: has a longer duration of action, but is
otherwise similar to vancomycin.
10. Nucleic Acid Inhibitors
Quinolones: are broad-spectrum antibiotics (effective
for G - bacilli & cocci, mycobacteria, mycoplasmas &
rikettsiae and G +ve bacteria).
Ineffective in most anaerobic infections.
(Unlike the 1st and 2nd ), 3rd generation is active
against streptococci.
4th generation slows development of resistance.
Metronidazole:
a variety of bacteria, amoebae, and protozoa
11.
12. Rifampicin
Mycobacteria (TB, non TB).
G + as (MRSA) in + fusidic acid.
G –ve as, N meningitidis, gonorrhoeae, Listeria, H
influenzae, Borrelia and Legionella p.
Fidaxomicin
G +ve especially clostridia.
13.
14. Tetracyclines: G+, G -, other as Rickettsia,
Chlamydia and Mycoplasma.
not used routinely for staphylococcal or streptococcal.
Tigecycline: G+, G- and anaerobes.
against multi-resistant antibiotics bacteries such as
MRSA and Acinetobacter. Not Pseudomonas spp. and
Proteus spp.
15. Aminoglycosides
Primarily against Gm –ve aerobic bacilli (Proteus,
pseudomonas, E.Coli, enterobacter, Klebsiella,
Shigella)
Only few G +ve cocci (staph aureus, strept-viridans
Not effective against G +ve bacilli, G-ve cocci and
anaerobes
Tuberculosis, Brucellosis, Tularemia, Plague, Malaria.
16. Macrolides
G+ve as Beta-hemolytic streptococci,
pneumococci, staphylococci, and enterococci,
Limited G-ve as Bordetella pertussis,
Haemophilus influenzae, Legionella pneumophila,
mycoplasma, mycobacteria, some rickettsia, and
chlamydia.
Chloramphenicol
• Meningitis, MRSA, topical use.
• Historic: typhus, cholera. Gram-negative, Gram-positive,
anaerobes.
19. New Classes of Antibiotics
Four new classes of antibiotics have been
brought into clinical use in the late 2000s and
early 2010s:
Cyclic lipopeptides (such as daptomycin),
Glycylcyclines (such as tigecycline),
Oxazolidinones (such as linezolid),
Lipiarmycins (such as fidaxomicin)
20.
21. Daptomycin
Binds to the membrane and cause rapid
depolarization, resulting in a loss of membrane
potential leading to inhibition of protein, DNA and
RNA synthesis.
G +ve , but it is inhibited by pulmonary surfactant so
less effective against pneumonias
30. Intrinsic Resistance
1. Lack target :
• No cell wall; innately resistant to penicillin
E.g Mycoplasma.
2. Innate efflux pumps:
• Drug blocked from entering cell or ↑ export of
drug (does not achieve adequate internal
concentration). Eg. E. coli, P. aeruginosa
3. Drug inactivation:
• Cephalosporinase in Klebsiella
It occurs naturally.
31. Acquired Resistance
Mutations
• It refers to the change in DNA structure of the gene.
• Occurs at a frequency of one per ten million cells.
• Eg. Mycobacterium.tuberculosis, Mycobacterium lepra
, MRSA.
• Often mutants have reduced susceptibility
32. Plasmids
• Extra chromosomal genetic elements can replicate
independently and freely in cytoplasm.
• Plasmids which carry genes resistant ( r-genes) are
called R-plasmids.
• These r-genes can be readily transferred from one
R-plasmid to another plasmid or to chromosome.
• Much of the drug resistance encountered in clinical
practice is plasmid mediated
33.
34. Mechanisms Of Drug Resistance
Can be broadly divided into:
1. Inactivation of the antimicrobial agent either by disruption of its
chemical structure (e.g. Penicillinase)
2. By addition of a modifying group that inactivates the drug (e.g.
Chloramphenicol, inactivated by acetylation).
3. Restriction of entry of the drug into the bacterium by altered
permeability or efflux pump (e.g. Sulphonamides, tetracycline).
4. Modification of the bacterial target – this may take the form of an
enzyme with reduced affinity for an inhibitor, or an altered
organelle with reduced drug-binding properties (e.g.
Erythromycin and bacterial ribosomes).
35. Decreased permeability: Porin Loss
Interior of organism
Cell wall
Porin channel
into organism
Antibiotic
Antibiotics normally enter bacterial cells via porin channels
in the cell wall
36. Decreased permeability: Porin Loss
Interior of organism
Cell wall
New porin channel
into organism
Antibiotic
New porin channels in the bacterial cell wall do not allow
antibiotics to enter the cells
42. Penicillin resistant Streptococcus
pneumoniae (PRSP)
Risk factors
◦ Age > 65 years
◦ Beta-lactam therapy in past 3 months
◦ Alcoholism
◦ Multiple medical comorbidities (e.g.
immunosuppressive illness or
medications)
◦ Exposure to a child in a day care centre.
43. Penicillin Resistant Streptococcus
Pneumoniae (PRSP)
Penicillin resistant (MIC > 2.0 mcg/ml)
◦ Vancomycin rifampin.
◦ High dose cefotaxime tried in meningitis.
◦ Non-meningeal infection: cefotaxime / ceftriaxone, high dose
ampicillin, carbapenems, or fluoroquinolone (levofloxacin,
moxifloxacin).
Multidrug resistant (MDRSP, resistant to any 2 of the following:
penicillins, erythromycin, tetracycline, macrolides, cotrimoxazole)
◦ Vancomycin rifampin
◦ Clindamycin, levofloxacin, moxifloxacin could be tried
45. ESKAPE pathogen
ESKAPE pathogen
(Enterococcus faecium, Staphylococcus aureus,
Klebsiella pneumoniae, Acinetobacter baumannii,
Pseudomonas aeruginosa, and Enterobacter species),
A group of pathogens with a high rate of antibiotic
resistance that are responsible for the majority of
nosocomial infections.
46. Pseudomonas Aeruginosa Antibiotics
1. Aminoglycosides: (gentamicin, amikacin,
tobramycin, but not kanamycin)
2. Quinolones (ciprofloxacin, levofloxacin, but not
moxifloxacin)
3. Cephalosporin (ceftazidime, cefepime,
cefoperazone, cefpirome, ceftobiprole, but not
cefuroxime, cefotaxime, or ceftriaxone)
47. 4. Antipseudomonal penicillins: carboxypenicillins
(carbenicillin and ticarcillin), and ureidopenicillins
(mezlocillin, azlocillin, and piperacillin). P.
aeruginosa is intrinsically resistant to all other
penicillins.
5. Carbapenems (meropenem, imipenem, doripenem,
but not ertapenem)
6. Monobactams (aztreonam)
7. Polymyxins (polymyxin B and colistin)
Pseudomonas Aeruginosa Antibiotics
49. Extensive Drug Resistant TB
MDR-TB (Multidrug Resistant TB)
◦ Resistant to isoniazid and rifampin
XDR-TB (Extensive Drug Resistant TB)
◦ In addition to resistance vs. isoniazid and
rifampin,
◦ Resistant to any fluoroquinolones, and
◦ At least one of three injectable second-line drugs
(capreomycin, kanamycin and amikacin).
50. Some resistant pathogens
Pseudomonas aeruginosa:
◦ One of the worrisome characteristic: low antibiotic
susceptibility
◦ Multidrug resistance common: due to mutation or
horizontal transfer of resitant genes
Acinetobacter baumanii
Multidrug resistance
Some isolates resistant to all drugs
Salmonella, Esherichia coli
Mycobacterium tuberculosis
53. Prophylaxis Of Infective Endocarditis
Indications:
Patients who previously had endocarditis, cardiac
valve replacement surgery (or surgically constructed
systemic or pulmonary shunts .
In the following procedures:
All dental procedures
certain genito-urinary, gastrointestinal, respiratory
or obstetric/gynaecological procedures.
54. Intravenous antibiotics are no longer recommended
unless the patient cannot take oral antibiotics.
For dental procedures, in addition to prophylactic
antibiotics, the use of chlorhexidine 0.2% mouthwash
five minutes before the procedure may be a useful
supplementary measure.
55. Antimicrobials for Infective Endocarditis
Prophylaxis
(AHA 2007)
Invasive Procedures for Prophylaxis in High-Risk Patients
Situation Agent Regimen (30-60 minutes before
procedure)
Oral Amoxicillin 2 g
Penicillin-allergic Cephalexin1 or 2 g
Clindamycin or 600 mg
Azithromycin 500 mg
Unable to take oral Ampicillin or 2 g IM/IV
Cefazolin or ceftriaxone 1 g IM/IV
Penicillin-allergic Cefazolin or ceftriaxone 1 g IM/IV
Clindamycin 600 IM/IV
56. GENERAL PRINCIPLES
1. Prophylaxis should be restricted to cases where
the procedure commonly leads to infection, or
where infection, although rare, would have
devastating results.
2. The antimicrobial agent should preferably be
bactericidal and directed against the likely
pathogen.
57. 3. The aim is to provide high plasma and tissue
concentrations of an appropriate drug at the time
of bacterial contamination. Intramuscular
injections can usually be given with the
premedication or intravenous injections at the
time of induction. Drug administration should
seldom exceed 48 hours.
4. If continued administration is necessary, change
to oral therapy post-operatively wherever
possible.
58. Meningitis Prophylaxis
For contacts of patients with H influenzae
meningitis
Rifampicin (10 mg/kg twice a day) (maximum, 1200
mg/d) for 4 days.
For contacts of patients with N meningitidis
meningitis
Rifampicin is also used, but the duration of therapy is
only 2 days.
An alternative to rifampin for adult contacts of patients with
meningococcal meningitis is a single 500-mg dose of
60. Prophylactic Rheumatic Fever
Primary prophylaxis
(treatment of streptococcal pharyngitis) dramatically
reduces the risk of ARF.
Secondary prophylaxis
Patients with a history of rheumatic fever are at a high
risk of recurrent ARF, which may further the cardiac
damage.
61. WHO guidelines
Rheumatic fever with carditis and clinically significant residual
heart disease :
requires antibiotic treatment for a minimum of 10 years after the latest
episode; prophylaxis is required until the patient is aged at least 40-45
years and is often continued for life.
Rheumatic fever with carditis and no residual heart disease
aside from mild mitral regurgitation :
requires antibiotic treatment for 10 years or until age 25 years
(whichever is longer).
Rheumatic fever without carditis:
requires antibiotic treatment for 5 years or until the patient is aged 18-
21 years (whichever is longer).
Children given penicillin G benzathine at a dose of 1.2 million U IM
q4wk
62. Recommendations For Prevention Of infection
In Asplenia (Or Hyposplenia)
1.Phenoxymethylpenicillin 250-500mg PO q12h OR
Amoxycillin 500mg PO q12h
2. Penicillin allergy - EES 400mg PO q12h OR
Azithromycin 250mg PO q24h
Duration:
Minimum 2 years post splenectomy is encouraged in
adults.
Up to 16 years of age in children.
Life long is not recommended
(McMullin 1993)
63. Emergency supply of antibiotic:
a) Amoxycillin 3g PO should be kept at home if
fever occurs OR
b) Cefuroxime 1g PO OR
c) Amoxycillin/Clavulanate 625mg PO OR
d) If taking EES, increase dose to 800mg PO
q12h OR
e) If taking Azithromycin, increase dose to
500mg PO q24h OR
f) Clindamycin 600mg PO OR
g) Trimethoprim/Sulphamethoxazole 960mg PO
67. Sepsis with no clear source
CULTURES
Pip/tazo (or Meropenem)
Or Cefepime ± Vancomycin (risk of MRSA)
± Gentamicin (Quinolones)
Severe PCN allegy
Azteronam or ciprofloxacin
+ Gentamicin
+ Vancomycin then ?????
68. CELLULITIS
Portal of entry of infection is seen
on the lateral thigh with necrosis
of skin; infection has extended
mainly proximally from this site.
69. Skin, Soft tissue and bone infections
Always Elevate
Cellulitis
Non suppurative
Microbiology ????
treatment
Amp/sulb
Or cefazolin
Or clindamycin
71. Biliary tract infection
Micro???
Community acquired
Ceftriaxone
Or Etrapenem
Or cipro
Hospital acquired
Pip/tazo
Or cefepime+ Metronidazole
Or Aztreonam+ metronidazole±Vancomycin
72. Pancreatitis
Micro
Not
Indication
Treatment
Pip/tazo
Or cefepime+ Metronidazole
Or cipro + Metronidazole
73. Peritonitis
Primary (SBP)
Secondary
Mild to moderate ???
Severe
Pip/tazo
Or cefepime+ Metronidazole
Or Vancomycin+ cipro + Metronidazole
Antifungal???
Tertiary
75. Piperacillin/tazobactam 3.375 g IV
q6h
Clinically stable
Cefepime 2 g IV q8h
Aztreonam 2 g IV q6h2 + vancomycin
+ gentamicin
Pencillin allergy with history of:
• Rash
• Anaphylaxis
Add vancomycin to regimen
• Severe mucositis or
• Suspected catheter-related infection
or
• Suspected skin or skin structure
infection or
• Gram-positive oganism in blood
cultures
Add gentamicin and vancomycin to
regimen
• Clinically unstable (based on BP,
HR, RR, and mental status)
Consider adding voriconazole• Fever 72 hours on broad-spectrum
antimicrobials.
Guidelines for Treatment of Febrile
Neutropenia
76. Pneumonia
HAP: Hospital-acquired pneumonia
◦ ≥ 48 h from admission
VAP: Ventilator-associated pneumonia
◦ ≥ 48 h from endotracheal intubation
HCAP: Healthcare-associated pneumonia
◦ Long-term care facility (NH), hemodialysis,
outpatient chemo, wound care, etc.
CAP: Community-acquired pneumonia
◦ Outside of hospital or extended-care facility
82. Healthcare-associated pneumonia, HCAP
Pneumonia that occurs in a patient with extensive
healthcare contact, one or more of the following:
◦ IV therapy, wound care, or IV chemotherapy within the
prior 30 days.
◦ Residence in a nursing home or long-term care facility
◦ Hospitalization in an acute care hospital for two or more
days within the prior 90 days
◦ Attendance at a dialysis clinic within the prior 30 days
84. Clinical Case
68-yo female with insulin-dependent diabetes
presents with 2-day history of fever, cough, and
pleuritic chest pain. She had knee replacement
surgery 60 days ago and spent 2 weeks at a
rehabilitation facility.
On exam, temp 101.8 F, HR 124, BP 110/76, RR 24
with O2 sat 92% on RA. She is alert and oriented
with NAD. Auscultation reveals RLL crackles. White
count 18,000 with L shift, BUN 32. CXR shows focal
consolidation in RLL.
What antimicrobial treatment should be initiated?
85. Treatment
Empiric treatment guidelines depend on whether
HAP is early or late onset (>4 days) and risk
factors for MDR pathogens present.
Risk Factors for Multi-Drug Resistant pathogens
• Antimicrobial therapy in preceding 90 days
• Onset of pneumonia after 5 days of
hospitalization
• High frequency of antibiotic resistance in the
community or hospital unit
• Duration of ICU stay and mechanical
ventilation
• Immunocompromised state
86. Treatment
For early onset with no MDR risk factors:
• Pathogens include S. pneumo, H. influenzae,
MSSA, E. coli, Enterobacter, Proteus.
• Recommended antibiotics:
Ceftriaxone
or Levofloxacin
or Unasyn
or Ertapenem.
87. Treatment
For late onset or MDR risk factors present:
• Pathogens include Pseudomonas, Klebsiella ESBL,
Acinetobactor, MRSA, Legionella.
• Recommended antibiotics:
Cefepime or imipenem or Zosyn
PLUS levofloxacin or gentamicin
PLUS vancomycin or linezolid
89. Clinical Case
68-yo female with insulin-dependent diabetes
presents with 2-day history of fever, cough, and
pleuritic chest pain. She had knee replacement
surgery 60 days ago and spent 2 weeks at a
rehabilitation facility.
On exam, temp 101.8 F, HR 124, BP 110/76, RR 24
with O2 sat 92% on RA. She is alert and oriented
with NAD. Auscultation reveals RLL crackles. White
count 18,000 with L shift, BUN 32. CXR shows focal
consolidation in RLL.
What antimicrobial treatment should be initiated?
90. Clinical Case
Patient was started on Cefepime, Levofloxacin, and
Vancomycin for HCAP with MDR risk factors. She is
at risk for MDR pathogens due to her history of
diabetes and recent knee surgery with subsequent
rehab.
On hospital day 3, sputum culture grew MRSA.
Cefepime and Levofloxacin stopped. After a 10-day
course of Vancomycin, patient improved and was
sent home.
91. Guidelines for Treatment of Pneumonia in Adults
durationDirected therapyPathogensSevere
Penicillin
Allergy
Empiric
Therapy
7-14 dPenicillin G
Azithromycin
Doxycycline
Cefuroxime
Doxycycline
Cefuroxime
Pneumococcus
Legionella
Mycoplasma
Haemophilus
influenzae
Chlamydia
pneumoniae
Moraxella catarrhalis
LevofloxacinCeftriaxone+
azithromycin
CAP
14 dAmp/Sulb or
Clindamycin
Mouth floraClindamycinAmp/SulbCAP
aspirati
on
8 dPip/Tazo+gentamicin
Pip/Tazo±gentamicin
Pip/Tazo
Pip/Tazo
Meropenem
Oxacillin
Pseudomonas A
Enterobacter sp
Serratia marcescens
Klebsiella sp
Acinetobacter sp
Staphylococcus A
Ciprofloxaci
n +
vancomycin
Pip/Tazo ±
vancomycin
±
gentamicin
HAP
VAP
92. Guidelines for Treatment of Infective
Endocarditis in Adults
Directed therapyPathogensSevere
Penicillin
Allergy
Empiric
Therapy
Penicillin G2 or ceftriaxone
Penicillin G2 or ceftriaxone
Ampicillin4 + gentamicin5
Ceftriaxone
Oxacillin ± gentamicin
Viridans
streptococci
Streptococcus
bovis
Enterococcus
HACEK group
Staphylococcus
aureus
VancomycinPenicillin
G
+gentamici
n
OR
ceftriaxone
Native
valve
Oxacillin+gentamicin
+gentamicin + rifampin5,6
Penicillin G7 or
ceftriaxone3± gentamicin5
Ampicillin4 + gentamicin5
Staphylococcus
aureus
Viridans
streptococci
SameVancomyci
n
+gentamici
n
+rifampin
PVE
93. Guidelines for Treatment of Bone
and Joint Infections in Adults
durationDirected therapyPathogensEmpiric Therapy
4-6 wk
4-6 wk
Oxacillin or
cefazolin
Ampicillin/sulbactam
Staphylococcus
aureus
Usually
polymicrobial
Vancomycin
Piperacillin/tazobac
tam+ vancomycin
Ampicillin/
sulbactam
Osteomyelitis:
Healthy
adult
Posttraumati
c
Diabetic foot
4 wk
2 wk
Oxacillin or cefazolin
Ceftriaxone
Staphylococcus aureus
Gonococcus
VancomycinSeptic arthritis
4 wkOxacillin or cefazolin
Vancomycin5
Penicillin G or
ampicillin
Staphylococcus aureus
Staphylococcus
epidermidis
Streptococcus
VancomycinTotal joint
replacement
99. Antibiotics in Pregnancy
DCB
Streptomycin D
Tetracycline D
Tigecycline D
Tobramycin D
Doxycycline D
Trimethoprim C
TMP/SMX2 C
Vancomycin C
Norfloxacin C
Pyrazinamide C
Pyrimethamine C
Rifampin C
Sulfisoxazole2 C
Gentamicin C
Levofloxacin C
Linezolid C
Clofazimine C
Daptomycin C
Chloramphenicol C
Ciprofloxacin C
Clarithromycin C
Meropenem B
Oxacillin B
Penicillin G B
Piperacillin/tazobactam B
Dicloxacillin B
Ampicillin/sulbactam B
Aztreonam B
Cefazolin B
Cefdinir B
Cefepime B
Cefixime B
Cefpodoxime B
Cefprozil B
Ceftriaxone B
Cefuroxime B
Cephalexin B
Clavulanate B
Clindamycin B
Quinupristin/dalfopristin B
Rifabutin B
Sulfadiazine2 B
Azithromycin B
Metronidazole1 B
101. Antimicrobials Contraindicated in Lactation
Chloramphenicol
Potential for idiosyncratic bone marrow suppression
Ciprofloxacin, norfloxacin
Ciprofloxacin is not currently approved for children.
Cartilage lesions and (quinolones) arthropathies were
seen in immature animals.
Metronidazole
Risk of mutagenicity and carcinogenicity. American
Academy of Pediatrics recommends discontinuing breast
feeding for 12 to 24 hours to allow drug excretion.
102. Liver and Antibiotics
Isoniazid
Nitrofurantoin
Augmentin
Other antibiotics have been reported to cause liver
disease. Some examples include minocycline, and
Cotrimoxazole.
104. The combination of imipenem and cilastatin has the potential to
cause seizures.
Aminoglycoside-induced ototoxicity, neuromuscular blockade and
respiratory depression, and further renal compromise.
Erythromycin, been associated with reversible hearing loss.
Vancomycin induce ototoxicity.
Ofloxacin and Lomefloxacin had risk of developing CNS
reactions.
penicillins, most cephalosporins, aztreonam, clarithromycin,
and trimethoprim and sulfamethoxazole require dose reduction.
Doxycycline, azithromycin, sparfloxacin, trovafloxacin, and
grepafloxacin require no alteration of dosage.
Renal Insufficiency