1. judicious use of antibiotics
presenter : Dr ES Wekesa,mmed urology, yr2
Moderator : Dr Loice Achieng, Consultant Physician
2. Outline
• Introduction
• brief history of antibiotics/resistance
• definitions
• ideal antibiotic
• antibiotic classes with mode of action
• pharmacokinetics
• resistance- factors and mechanisms
• prevention of antibiotic resistance
• antibiotics use in surgery
3. introduction
• The misuse of antibiotics is a major driver of some emerging infections e.g.
Clostridium difficile, the selection of resistant pathogens in individual patients,
and for the continued development of antimicrobial resistance (AMR) globally
• The growing emergence of multi-drug resistant organisms has lead to
alarming implications, especially with regards to Gram-negative bacteria
including extended-spectrum beta-lactamase (ESBL)-producing Escherichia
coli and Klebsiella species.
• appropriate use of antimicrobials maximizes the utility and therapeutic
efficacy of treatment, and minimizes the risks associated with emerging
infections and the selection of resistant pathogens.
4. brief history of antibiotics
• The use of antibiotic-producing microbes to prevent disease stretches back ,
with traditional poultices of mouldy bread being used to treat open wounds in
Serbia, China, Greece and Egypt more than 2000 yearsago.
• The Eber’s papyrus from 1550 BC is the oldest preserved medical document
and includes mouldy bread and medicinal soil amongst its list of remedies.
• An Anglo-Saxon recipe from 1000 years ago was also recently shown to kill
MRSA
• The development of anti-infective drugs and the underlying concept of
chemotherapy is widely accredited to Paul Ehrlich, who developed the
synthetic arsenic-based pro-drugs salvarsan
5.
6.
7.
8. definitions
• An antibiotic agent is usually considered to be a chemical substance
made by a microorganism that can inhibit the growth(static) or kill
microorganisms(cidal).
• An antimicrobic or antimicrobial agent is a chemical substance similar
to an antibiotic, but may be synthetic.
• MIC-the lowest concentration of an antimicrobial that will inhibit the
visible growth of a microorganism after overnight incubation,
9. ideal antimicrobial agent
• soluble in body fluids
• selectively toxic - Drugs that specifically target microbial processes,
and not the human hosts
• nonallergenic
• reasonable half life (maintained at a constant therapeutic
concentration)
• unlikely to elicit resistance,
• has a long shelf life,
• reasonably priced.
10.
11. Beta-Lactams
• e.g penicillins, cephalosporins
• interfer with the synthesis of peptidoglycan, an important component
of the bacterial cell wall, and are mostly used against gram-positive
bacteria. Bacteria can, however, develop resistance to beta-lactams
via several routes, including the production of enzymes that break
down the beta-lactam ring
12. Sulfonamides
• e.g. prontosil, sulfanilamide, sulfadiazine
• broad-spectrum antibiotics capable of acting on both Gram-positive
and Gram-negative bacteria. Unlike the beta-lactams, they act by
inhibiting bacterial synthesis of the B vitamin folate, thus preventing
growth and reproduction of the bacteria
13. Aminoglycosides
• e.g. streptomycin, kanamycin
• inhibit the synthesis of proteins in bacteria, eventually leading to cell
death. They are only effective against certain Gram-negative bacteria,
as well as some Gram-positive bacteria
14. Tetracyclines
• broad-spectrum antibiotics, active against both Gram-positive and
Gram-negative bacteria. Like the sulfonamides, they inhibit protein
synthesis, inhibiting growth and reproduction of bacteria. Their use is
decreasing due to increasing instances of bacterial resistance
• They must be taken in isolation, often two hours before or after
eating, as they can easily bind with food, reducing their absorption
• e.g. limecycline, doxycycline
15. Chloramphenicol
• acts by inhibiting protein synthesis, and thus growth and
reproduction of bacteria. However, it is also bactericidal against a
limited number of bacteria.
• Due to the possibility of serious toxic effects, in developed countries it
is generally only used in cases where infections are deemed to be life-
threatening
16. Macrolides
• they are mainly effective against Gram-positive bacteria; however,
they act in a bacteriostatic manner, preventing growth and
reproduction by inhibiting protein synthesis.
• e.g. erythromycin,azithromycin
17. oxazolidinones
• are active against Gram-positive bacteria, and act by inhibiting
protein synthesis, and hence growth and reproduction.
• e.g. linezolide and cycloserine
18. newer antibiotics
• plazomicin, eravacycline, temocillin, cefiderocol,
ceftazidime/avibactam, ceftolozane/tazobactam,
meropenem/vaborbactam, and imipenem/relebactam - most are
effective against active against ESBL, and almost all of them are
active against CPE
22. factors leading to drug resistance
• Overuse or unnecessary use of antibiotics eg asymptomatic catheterized
• Use of newer antibiotics for simple common infections
• Lack of recognition of risk of resistance to organisms colonizing patient but not direct
targeted indication
• Reluctance to narrow spectrum of antibiotics after culture and sensitivity results
reported; ignoring susceptibility data
• Over-the-counter availability of antibiotics
• Inadequate dosing leads to inadequate response, which leads to longer exposure
• Inadequate dosing leads to subMIC, which leads to resistance(gene expression, efflux,
permeability mechanisms)
23. Mechanisms of Resistance
• Alteration of Targets – usually affects ribosomes eg penicillin binding
proteins
• Alteration of Membrane Permeability- Change in the receptor that
binds the drug
• Development of Enzymes – β-lactamase
• Efflux pumps – Membrane proteins many Gram negatives that pump
out drug
• Alteration of Metabolic Pathway – Development of alternate pathway
26. Diagnosis
• Antimicrobial use should be confined to appropriate clinical
indications.
• Inappropriate uses such as uncomplicated viral infections should be
avoided. Remember, for example,pyrexia and leukocytosis are not
specific for bacterial infections.
• If antibiotics are not resolving the clinical signs, consider that you
may have the wrong diagnosis or look for an underlying/predisposing
disease.
27. Drug
• Use as narrow-spectrum of antimicrobial as possible.
• Use culture and antimicrobial susceptibility results to aid in the
selection of antimicrobials.
• Consider the distribution and penetration of the drug and which
bacteria are likely to be involved (e.g. anaerobic/aerobic, gram
+/gram when selecting an antibiotic
• Consider topical creams/shampoos rather than oral antimicrobials
whenever possible.
28. Dose
• right dosage, intervals
• use of auc/mic and peak/mic ratio in concentation dependent and
longer infusion time in time dependent
29. Duration
• To minimize selective pressure, therapeutic exposure to
antimicrobials should be minimized by treating only for as long as
needed for the desired clinical response.
• Treat long enough and at a sufficient dose – i.e.avoid under dosing.
30. Limiting Resistance
• Constant exposure to high levels of antibiotic
• Use of multiple antibiotics
• Restricted use of antibiotics
32. Classification of Operative Wounds and Risk of
Infection
• Clean- elective, not emergency, nontraumatic, primarily closed; no acute inflammation; no break
in technique; and respiratory, gastrointestinal, biliary and genitourinary tracts not entered. e.g.
breast biopsy,hernia repair, risk< 2%
• Clean-contaminated- urgent or emergency case that is otherwise clean; elective opening of
respiratory, gastrointestinal, biliary or genitourinary tract with minimal spillage (e.g.,
appendectomy) not encountering infected urine or bile; minor technique break.e.g
cholecystectomy, risk< 10%
• Contaminated - nonpurulent inflammation; gross spillage from gastrointestinal tract; entry into
biliary or genitourinary tract in the presence of infected bile or urine; major break in technique;
penetrating trauma < 4 hours old; chronic open wounds to be grafted or covered. risk~ 20%
• Dirty-purulent inflammation (e.g., abscess); preoperative perforation of respiratory,
gastrointestinal, biliary or genitourinary tract; penetrating trauma > 4 hours old. risk~ 40%
33. Questions to Ask Before
Prescribing Antimicrobials
• Does the condition necessitate antimicrobial treatment?
• Are there other options besides antimicrobial treatment (such as
incision drainage)?
• Will the potential risk of inducing resistance outweigh the benefit of
treatment?
• Is the proposed treatment likely to work against the pathogen
involved?
• Are there any risks to public health from antimicrobial treatment?
34. Surgical Indications
• Antimicrobials are not a substitute for poor surgical asepsis.
appropriate criteria for perioperative antibacterial use include:
• Prolonged surgical procedures (>1.5 hours)
• Introduction of an implant into the body
• Procedures where introduction of infection would be catastrophic (e.g. central nervous
system surgery)
• Cases with an obvious identified break in asepsis
• Bowel surgery with a risk of leakage
• Dentistry with associated periodontal disease
• Contaminated wounds
35. antibiotic prophylaxis
• antibiotic alone not able to prevent surgical site infections- other
strategies to be employed- source control
• only administered for operative procedures that have high rate of
postoperative wound infection, or when foreign materials are
implanted
• drugs used should be effective against the pathogens most likely to
contaminate the surgical site
• broad spectrum antibiotics should be avoided, with a single dose
sufficient given 30-60 minutes prior,additional antibiotics given
intraoperatively for prolonged procedures
36.
37. antibiotic therapy
• only used after a treatable surgical infection has been recognized or if there is
high degree of suspicion of an infection
• source of infection should be investigated and controlled as soon as possible
• empiric antimicrobial therapy should be started in those with surgical
infection- awaiting culture and sentivity
• targeted antibiotic therapy regimens should be used when antimicrobial
susceptibility test results available
• diagnostic investigations in patients with clinical features of sepsis
• use narrow spectra for community acquired and broad spectra for hospital
acquired
• infection control measures and antimicrobial stewardship programs should be
implemented and regularly enforced
