a presentation given during my infectious disease residency

1. ANTIBOITIC GENERAL REVIEW
AND
ANTIBOTIC RESTISTANCE
BY DR ALSALHEEN ALRAIED– 31/DEC/2017

2. DEFINTION
MAJOR CLASSES
MECHANISM
CHARACTERISTIC OF
COMMON TYPES
Antibiotic quick guide
review
PART 1
OBJECTIVES:
BACKGROUND
EPIDEMIOLOGY OF
COMMON REISISTANCE
STRAIN
ANTIMICROBIAL
STEWARDSHIP PROGRAM
MAIN ELEMENT
DE –ESCLATION THERAPY
PART 2

3. definition:
Antibiotics can be naturally produced, semi-synthetic, or synthetic substances
Designed to have as much selective toxicity on the bacteria as possible
treatment of an infection before specific culture information has been reported or
obtained
Empiric therapy
antimicrobial policy consisting of the initial use of wide-spectrum antimicrobials
followed by a reassessment of treatment when culture results are available
De-esclation therapy:
Bactericidal: kill bacteria
Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them
immediately; will eventually lead to bacterial death
Bactericidal vs bactreriostatic
Part 1

4. classification

5. macrolidequinolonesB-lactam and its
deravatives
Aminoglycoside
And
trimethoprime-
suphamethoxazole
classification
Important massage
1- Before choosing treatment consider patient presentation rather than risk factor
2- b-lactam antibiotics have greater efficacy than other classes .
3- bactrriostatic vs bacteriostatic
Cidal: B-lactams, aminoglycosides, quinolones
Static: tetracyclines. Macrolides, lincosamides

6. B-lactam: penicillin and derivatives
Penicillin( G,V, benzathine) cover strep-
viridance,streptococcal pyogenes, oral anaerobs, syphilis,
leptospira
AMPICILLIN, AMOXICILLINE
Cover same oraganism plus HELP
H-influenza- Ecoli- Listeria –Proteus –salmonella.
penicillin
Againist staph aureus except MRSA
Oxacillin , cloxacillinin and nafcillinin
Penicillinase resistant penicilline
Pipracilline- ticarcillin- azlocilline
Mezlocilline- cover gram negative as
well as pseudomonas.
Best initial therapy for:
Cholecystitis
Pyelonephritis
Ventilation associated pneumonia
Neutropenic fever.
Antipseudomona pecillince

7. Include: cefotetan,cefoxitine,cefaclor,cefuroxime
Cefotetan, cefoxitine: best intial therapy ffor PID, BEST FOR
ANAEROBIC INFECTION
Other drugs such as cefuroxime and cefaclor are used for
respiratory infections
Include: ceftriaxone. Cefotaxime, ceftazidime:
Ceftraixone: first line for pneumococcus including (
meningitis- community acquired pneumonia-
gonorrhea- lyme disease)
Cetaxime given in case of sponatnous bacterial
peritonitis because it doesn’t need hepatic
metabolism, ceftazidimen: has antipseudonal
coverage
Include cefepime: hase better staph coverage used in
neutropenic fever and VAP.
B-lactam: cephalosporine.
Methicelline senstive= cephalosporine sensitive
Streptococus except enterococcus
Some gram negative weak effect
Include: cefazolin, cphalexine,cephadrine,cefadroxyle
First generation
second generation
third generation
forth generation
fifth generation:
Ceftarolin
Mainly
G +VE
Mainly
G -VE
Cover
MRSA

8. Other B-lactam and B-lactamase combination.
01
03
Carbebenem: imepenem,
meropenem, ertapene,doripenem
Cover all gram negative except ertapenem(
pseudomonas) and anerobes and grame prositive.
B-lactam and B-lactamase combination.
Clavunate and sulbactam and tazobactam.
Adds coverage against sesteive staph and anerobes
They are first choice in MOUTH AND GI abscess
Aztreonam (monobactam)
Exclusively for gram negative bacilli including
pseudomonas, no cross reaction with penicillin.
02

9. Others antibiotics
Include : gentamycin
,tobramycin , amikacine
Gram negative
(bowel,urine)
Synergistic with b-lactam
for enterococcus and staph.
Aminoglycoside
First choice for : cystitis
except in pregnancy
nitrofurantoin is first
choice
PCP as treatment and
prophylaxis
Trimethoprime/sul
phamethoxazole
cirporfoxacine:
most aerobic gram negatives including
Pseudomonas.
penetrates CNS, prostate, lungs
Non-ciprofloxacin : Ofloxacin,
Levofloxacin, Moxifloxacin,Gemifloxacin
great for respiratory pathogens, most
enteric gram negatives
Only levofloxacin covers pseudomonas
Covers some atypical: Mycoplasma,
Chlamydia, Legionella
quinolones
Erythromycin,
Clarithromycin,
Azithromycin
Broad spectrum against
gram positives
Good for atypical oganism
such as Mycoplasma,
Chlamydia, Legionella
Covers N.gonorrhea, H flu,
Legionella
Macrolides
Metronidazole :
No aerobic activity
Does not stand alone for mixed infections
Good coverage of anaerobes
Can be used for C diff, parasites, bacterial vaginosis

10. Antibiotic Coverage Quick Guide
Aminoglycosides
Cephalosporins: Ceftazidine,
Cefepime
Fluoroquinolones: Cipro,
Carbipenems: Imipenem,
Meropenem
Aztreonam
Colistin
1-Gram negative
pseudomonas
Flagyl – PO
Clindamycin – PO
Augmentin – PO
Carbipenem
Moxifloxacin
Tigecycline
2. Anaerobes:
TMX/SMX
Clindamycin
Doxycyclin
Vancomycin
Linezolid
Tigecycline
Daptomycin – cannot use in
lungs!
3- MRSA
Linezolid
Tigecycline
Daptomycin
Ceftaroline
3- VRS

11. Induction of SEIZURES in
overdose or renal
dysfunction
Cilastatin- inhibitor of
renal dehydropeptidase at
the kidneys to avoid
imipenem's metabolism to
a nephrotoxic metabolite
What major side effect
can Imipenem cause on
the CNS?
QT prolongation due to
interference with Ca++
(chelation)
What side effect do
quinolones have on the
heart?
Cefoxitine and cefotetan
deplete prothrombine and
increase risk of bleeding
What's effect of
cephalosporin on
bleeding?
Other important side
Effects to remember.
Linozolise : cause
revesiblen bone marrow
suppression
Daptomycine : increase
CPK level
Chronic metronidazole
use:
Convulsion and peripheral
neuropathy
Important side effects to remember

12. Community acquired
Pneumonia outpatient setting:
Macrolide (or fluoroquinolone
if already treated with
macrolide)
. Community acquired
Pneumonia inpatient setting:
fluoroquinolone (or ceftriaxone +
macrolide)
Community
acquired therapy
UTI:
Tmp-smx or nitrofurantoin
(fluoroquinolone are 2nd
choice)
Urinary tract
infections
Endocarditis:
Gentamicin + Vancomycin
endocarditis
Meningitis in adults:
Gentamycin + Ceftriaxone
meningitis
Empiric therapy

13. Useful books and apps for
prescribing antiboitics

14. • Last line in antibiotic resistance under threat - News update
• Tuesday December 22 2015
• BBC News has reported that "bacteria that resist the most common antibiotic of last resort –
• colistin [see below] – have been discovered in the UK“
• ttps://www.nhs.uk/news/medication/last-line-in-antibiotic-resistance-under-threat-news-update/
• The 70-year-old returned to the US state of Nevada in August 2016 after an
extended trip to India, where she was reportedly been hospitalised multiple
times.
• Although she was admitted to a hospital's acute care ward shortly after her
return, she died in September-2017 after her infection proved resistant to 26
different antibiotics.
• http://www.independent.co.uk/life-style/health-and-families/health-
news/woman-killed-superbug-resistant-every-antibiotic-india-visit-nevada-
hospital-dies-cdc-drugs-a7525531.html
URGENT NEWS
BBC: report
Independent
newspaper

15. Part 2

17. case
On admission she was hypotensive with BP 60/40
mm Hg, T-101oF , Pulse 140, RR 24, weight 60 kg
HEENT normal
Lungs CTA, no murmur
Left sided CVA tenderness, BS+
Neuro intact
Laboratory
WBC 21,000/µL, 40B, platelets 274,000/µL,
HB 8.5 g/dL
PT/PTT 24.6/51.7
Creatinine 6.2 mg/dL (was 1.2mg/dL 6
months ago), HCO3 16mmol/L, pH 7.2
u/a pyuria and bacteriuria, nitrite negative,
negative ketones
ALT 28 U/L, alb 2 g/dL, lactate 4 mg/dL,
glucose 48 mg/dL
Imaging
CXR clear
Case continued
Case presentation
64 y/o female admitted for weakness, fever,
incontinence, and syncope. 10 days patient
was seen by local MD for
flank pain and dysuria.
She was diagnosed with probable
pyelonephritis and started on PO
ciprofloxacin.
Over the week she became weaker,
had decreased appetite, and developed
fever.
PMH of recurrent UTIs-last hospitalized 6
months earlier with pyelonephritis. She has
DM, HTN, and hyperlipidemia (HLD)
Question is :
What antimicrobial would you
prescribe?
a. Aminoglycoside.
b. Broad-spectrum
cephalosporin.
c. Carbapenem.
d. Fluoroquinolone.
e. None of the above.

18. This patient was resistant to
flouroquinolone due to
inappropriate use of
antibiotic
Continue the case
First 8 hours:
Given 2 liters in first hour-still
hypotensive and norepinephrine was
started
Blood cultures drawn Urine culture sent
Ciprofloxacin given
Repeat glucose 127 mg/dL, plat
↓83,000, WBC ↓ 9900
Lactate 4 →7.6 →15.9 mg/dL
Platelet 83,000→45,000→13,000/µL
ALT 57 →2518 U/L
Blood and urine E. coli R-amp, amp/sulb,
fluoroquinolones (FQ) at 48 hours
Case:
And now the rest
of the story
Risk Factors for FQ Resistance
Hospitalization in previous 12
months OR
FQ use in previous 12 months OR
Prior documented FQ-resistant
organism
Johnson L et al. Am J Med. 2008;
121: 876-84.
Massage

19. background
In 2000, Nobel Laureate Dr. Joshua Lederberg wrote in the
journal Science that “the future of humanity and microbes
will likely evolve as episodes…of our wits versus their
genes”

20. background

21. Epidemiology: main
pathogens
ANTIMICROBIAL RESISTANCE
Global Report on Surveillance 2014(WHO)
Streptococcus pneumoniae/
- non-susceptible or resistant
To penicillin
Pneumonia –meningitis and otitis
Nontyphoidal Salmonella/
- vs fluoroquinolones
Shigella species/
- vs fluoroquinolones
Food born diarrhea
Escherichia coli/
- vs 3rd gen. cephalosporins
- vs fluoroquinolones
UTI-blood stream infection
Klebsiella pneumoniae/
- vs 3rd gen. cephalosporins
- vs 3rd carbapenems
Pneumonia and blood stream
infections
ESKAPE
mnemonic: Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas,
and ESBL (Enterobacter and E. coli)

22. Mechanism of resistance
Enzymatic inactivation
For example: b-lactamase
activity, and aminoglycoside –
modifying enzyme
Altered target site
Changes in : penciline target
site, ribosomes, DNA gyrases,
topoisomerase
Decrease permeability
Efflux pump up-
regulations

23. 1
2
3
4
IDSA
recommendations
New Regulatory Approaches to Facilitate
Antimicrobial Development and Approval
Strengthening Activities to Prevent and
Control Antimicrobial Resistance
Significant Investments in Antimicrobial-
Focused Research
Enhancement of Antimicrobial Resistance
Surveillance Systems
Greater Investment in Rapid Diagnostics R&D and
Integration into Clinical Practice
Combating Antimicrobial Resistance: Policy Recommendations to Save Lives
Infectious Diseases Society of America (IDSA)
Clinical Infectious Diseases, Volume 52, Issue suppl_5, 1 May 2011, Pages S397–S428,

24. Core Elements for Antibiotic Stewardship Programs
http://www.cdc.gov/getsmart/healthcare/implementation/core-
elements.html
ANTIMICROBIAL STWARDSHIP PROGRAM
Evidence-based guidelines for implementation
and measurement of antibiotic stewardship
interventions repared by a multidisciplinary
expert panel of the Infectious Diseases Society
of America and the Society for Healthcare
Epidemiology of America
TO Insure to get antibiotic when needed with
right drug , dose and duration
SPECIFIC PROGRAM TO MININMIZE RESISTANCE
A multidisciplinary ASP team should include an
ID physician and pharmacist as determined by the
institution
Two core strategies were recommended
Prospective audit with intervention and
feedback
Formulary restriction and preauthorization
https://academic.oup.com/cid/article/62/10/e51/246
2846

26. Antimicrobial Stewardship
Goals
Improve patient outcomes
Optimize selection, dose and
duration of Rx
Reduce adverse drug events
including secondary infection (e.g.,
C. difficile infection)
Reduce length of stay
Reduce health care expenditures
21 3 4
Reduce morbidity and mortality
Limit emergence of
antimicrobial resistance

27. ASP framework

28. Re-assement
Trigger tool to stop and
reassess antibiotic therapy
Guided assessment at 72 hr
Design of a `day 3 bundle` to improve the
reassessment of inpatient empirical
prescriptions

29. Advantages
Allows initial use of broad-
spectrum therapy
Narrows therapy when
appropriate
May influence future
prescribing behavior
Decreases inappropriate
use of antimicrobials
Reduces adverse events
May save money overall
Disadvantages
Prescribers may be
reluctant to change
therapy if the patient is
doing well
If not done correctly, may
narrow therapy
“inappropriately”
The most common
reasons for not de-
escalating:
•Lack of conclusive
microbiology results
–Continued use of
broad-spectrum
antimicrobial therapy
•Diagnostic uncertainty
–Treatment of fever,
colonization and/or
contamination
•Insecurity
–Treatment of
noninfectious
syndrome associated
with fever
•Duration longer than
necessary
De-escalation therapy

30. Make sure you try
to collect cultures
before starting
antibiotics
Many antibiotics
require renal
dosing, such as
vancomycin. If
you’re unsure the
dose call the
pharmacist.
ID approval is
required for many
antibiotics such as
vancomycin,
levofloxacin,
ciprofloxacin. Call
the ID fellow for
approval when
required.
Use your Sanford
Guide and
hospital
antibiograms to
help guide you.
Sanford Guide
now has an app
for i-phones –
very useful on the
wards!
Try to de-escalate
the antibiotic
after availibilty of
the culture
USEFUL TIPS

31. Thanks for your attention
https://www.youtube.com/watch?v=9Qu21F0hDJo
https://academic.oup.com/cid/article/62/10/e51/2462846#89046245
https://academic.oup.com/cid/article/52/suppl_5/S397/318402
http://www.idsociety.org/Guidelines/Patient_Care/IDSA_Practice_Guidelines/An
timicrobial_Agent_Use/Implementing_an_Antibiotic_Stewardship_Program/
Combating Antimicrobial Resistance: Policy Recommendations to Save Lives
Infectious Diseases Society of America (IDSA)
Clinical Infectious Diseases, Volume 52, Issue suppl_5, 1 May 2011, Pages S397–
S428,
http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html
https://academic.oup.com/cid/article/62/10/e51/2462846