The document discusses antibiotics-induced nephrotoxicity and its impact on kidney function, emphasizing the vulnerability of the kidneys to drugs, particularly antibiotics. It outlines acute kidney injury (AKI) symptoms, classifications, and causes, alongside chronic kidney disease (CKD) prevalence and its implications. The document also provides insights into the adjustment of antibiotic dosages based on renal function, highlighting the importance of monitoring and managing patients with renal failure.

1. Antibiotics induced
Nephrotoxicity (Renal Failure)
DR MANOJ KR CHOUDHARY
Ex SR Nephrology, IGIMS,PATNA
SR (Medicine) ,VIMS

2.  The kidney are the main organ of the body by which
drugs and their metabolites are eliminated from the
body.
 The kidney is particularly vulnerable to antibiotics and
other agents that cause renal damage.
 The heart pumps approx 25% of cardiac out put into
the kidney.
 Any drugs in blood will eventually rich the highly
vascularised kidney & potentially cause drug induced
renal failure.
INTRODUCTION

3. CONTINUE…
 Antibiotics induced renal injury can present as AKI
,Nephrotic Syndrome, Acute Tubler necrosis or CRF.
 Medication used account for 2% of hospital admission for
AKI & up to 15% ICU admission.

5. Acute Kidney injury
 Characterized by sudden impairment of kidney function
(within 48hrs) resulting in retention of nitrogenous waste
products .
 AKI complicate 5%-7% of acute care hospital admission
and up to 30% of ICU admission.
 Presented with S.creatinine & Blood urea during
biochemical screening.
 C/F- Nausea ,vomiting, anorexia ,confusion,coma etc.
 oliguria,anuria,vasculits rash or multiorgan failure.

6. Causes of AKI
 Pre renal- Hypovolemia &hypotensive shock,Renal A
emboli & Renal A Stenosis
 Renal- Vasculitis(SLE,PAN) ,Glomerlo nephritis,
-ATN, Sepsis.
 Post Renal- Uretric stone,UB tumor,Prostatic
hypertrophy, Urethral stricture

7. CLASSIFICATION OF AKI
 RIFLE CRITERIA-
 Risk- GFR >25% ,Urine out put<0.5ml/kg/hr for6hr
 Injury-GFR>50% ,Urine out put<o.5ml/Kg/hr for24hr
 Failure-GFR>75% ,Urine out put<0.3ml/Kg/hr for24hr
 or anuria for 12hrs
 Loss-peristent loss of kidney funtion>4wks
 ESRD- Dialysis dependent>3 months

8. INVESTIGATION & TREATMENT
 Routine Lab test-( BUN& Creatinine etc)
 USG ABDOMEN
 KIDNEY BIOPSY
 Treatment- Underlying cause
 Correction of fluid & electrolyte balance
 Dialytic support

10. Chronic Kidney Diease
 Global Public Health Problem
 Incidence & Prevalance of CKD is increasing
 CKD affects more than 20 million American or one in
nine adult.
 Most are unware of the condition because they remain
Asymptomatic until the disease is near end stage
condition.

11.  The estimated prevalence of CKD is about 8-16 % in
adult over age of 30 year as per WHO.
 In India estimated Prevalance is alarming .
 The Prevalance of CKD IS 17.2 in Urban population.
 It is estimated that every year approx. 200000 new
cases of ESRD are added to our population.
 It is estimated that there are 55,000 patient on dialysis
in India.

12.  Kidney Damage for ≥ 3 month
 As defined by structural or functional abnormalities of
Kidney.
 GFR less than 60 ml/min/1.73m2 for ≥3 month
 Bilateral small or echogenic Kidney on USG in
advanced stage

13. Stages of Kidney Disease
Stage Description GFR (mL/min/1.73 m2)
1 Kidney damage with
normal GFR
≥90
2 Kidney damage with
mild ↓ in GFR
60-89
3 Moderate ↓ GFR 30-59
4 Severe ↓ GFR 15-29
5 Kidney Failure <15 (or dialysis)
Adapted from the National Kidney Foundation

15. Leading causes of CKD
 Diabetic glomerular disease
 Glomerular Nephritis
 Hypertensive Nephropathy
 ADPKD
 Other cystic and tubulointerstitial Nephropathy

16. INVESTIGATION
 Renal Function test –Scr. , B. Urea, R/E etc.
 Electrolyte Panel –Na+, K+, Ca
 Iron Profile, Lipid Profile, Viral Marker
 Serum & Urine Electrophoresis &Immune fixation
 Antinuclear Antibody
 USG with or without arterial doppler
 Kidney Biopsy
 ABG

17. TREATMENT
 History & Physical Examination
 Slow rate of progression of Renal Damage
 Minimize Cardiovascular risk
 Strict control of Blood Sugar & Blood Pressure
 Management of Anemia & Dyslipidemia
 Identify & Treat complication
 Start planning & education for dialysis
 Start planning & education for Tx if appropriate

19. Objective for antibiotics prescription in Renal Failure
 Explain the necessity of dose adjustment during R I.
 Demonstrate how to calculate GFR using various
means
 Compare various type of dialysis and there dose
adjustment.
 Recognize risk factor for drug related adverse events
in patient with renal failure
 If possible avoid nephrotoxic antibiotics.

20. Calculating GFR
 The amount of blood flow filter by Glomerulus in a
given time (GFR 120-130 ml/min)
 GFR as overall major of renal function
 Exogenous markers like inulin not used widly
 GFR:- Most accurate measurement of Kidney function
 2 current technique used to estimate renal function
- Modification of Diet in Renal Diease (MDRD)
= Estimate GFR
- Cockroft-Gault Formula
= Estimate creatinine clearance

21. Cockroft Gault Formula
CrCl (ml/min)= (140-age)x (BW in kg)(x0.85if female)
72x Scr(mg/dl)
 Measure the rate of creatinine clearance via glomerulus
 Easy to make dose recommendation
 Easy to calculate
 Cockroft Gault is less accurate than MDRD in older &
obese people.

22. Renal Excreation of Antibiotics
 The principal process that determine Urinary excreation
of drugs are :- a) Glomerular filtration
b) Active tubular secretion
c) Passive or acute tubular reabsorption
 Renal disease affect Pharmokinatics process (ie. Drug
absorption, Drug distribution & metabolism)
 Uremia decrease GI absorption of drug
 Gastroparesis, Nausea, Vomating & Anorexia may all
reduce drug reabsorption

23.  Impaired renal function is associated with change in
binding of drugs to plasma protien
 The reduced protein binding accurse when renal
function impaired for the following reason:-
a) Reduction in serum albumin concentration
b)Structural change in binding sites
c) Displacement of drug from albumin binding site by
organic molecule that accumulate in uremia.
 Renal failure alters the metabolic clearance of the
drug.

24. Polar drug= water soluble
Non polar drug = lipid
soluble

25. ANTIMICROBIAL
Antimicrobial Usual dose CrCl mg/min Dose adujustment
Amikacin 7.5mg/kg/day
q12hrly to
(500mg)q 12hrly
>50-90
10-50
<10
No adjustment
7.5mg/kg /day q 24
hrs
7.5mg/kg/day q 48
hrs
Gentamicin Systemic and UTI
3mg/kg/day upto
80mg q8 hrly
Lifethreating
infection
5mg/kg/day then
3mg/kg/day
>70
35-70
24-34
16-23
10-50
5-9
80mgq8hr
80mg q12hrly
80mg q18hrly
80mgq24hrly
80mgq36hrly
80mgq48hrly

26. FLUROQUNILONES
Antibiotics Usual Doses CrCl Dose adujustment
Ciprofloxacin 400 mg(i.v)
Q 8-12 hrly
50-80 ml/
10-50 ml
<10ml
No change
400mg(i.v)q12 hrs
500mg(po)q 12hrs
400mg(i.v)q 24hrs
500mg(po)q 24hrs
Livofloxacin 500-750 mg
i.v/po
Q 24hrs
50-80ml
10-50ml
<10ml
No changes
250 (iv/po)q24 hrs
250(i.v/po)

27. Ofloxacin
Usual dose-400mg I,v/ po q
Cr Cl- 50-80ml/m-400mg i.v/po q24 hrs
Crcl-10-50 mg/ml – 400mg q 24 hrs
CrCl < 10 mg/ml-200mg q 24 hrs
Moxifloxacin
Usual dose
400mg(i.v/po) q 24 hrs
No change

28. Macrolides
 Broad spectrum, orally active
 Most are gram +ve & few gram –ve
 Erythromycin- usual dose 1gm iv q6h,500(po)q
 Crcl-50-80ml=No damage
 Crcl-10-50ml=No damage
 AZITHROMYCIN- usual dose-500mg iv/po
 -50-80ml- no damage
 -10-50ml- no damage

29.  Clarithromycin- 500mg(po)q12
 Crcl - 10-80-no damage
 <10- 250(po)q12h
 POLYMYXIN –
 COLISTIN- more active against P.aeroginosa
 cell membrane altering antibiotics
 Usual dose- 1.7mg/kg(iv)q 8hrly
 Crcl-40-60-2.5mg/kg iv q12
 Crcl-10-40-2.5mg/kgq24
 Crcl-<10ml/min-1.5mg(iv)q36

30. Antibiotics
 COLISTIN- usual dose-1.7mg/kg(iv)q8hrly
 Crcl-40-60-2.5mg/kg ivq12
 Crcl-10-40-2.5mg/kgq 24
 Crcl-<10mg/ml- 1.5mg(iv)q36
 VANCOMYCIN-
 Usual dose-(1gm) iv q12h
 Crcl-50-80ml-500mg ivq12h
 Crcl-10-50-500ivq 24h
 Crcl-<10-1gm(iv)q weekly

31.  TEICOPLANIN- new glycopeptide,active against gm+
bacteria only. Usual dose=400mg 1st day than
200mgdaily.
 Crcl-40-60- half of normal dose q24hly
 <40- the third of normal dose.
 LINEZOLID- t/t of resistent of gram+ve coccal&bacillary
infection
 Usual dose-600mgq12h
 No dose adjustment required
 TIGEICYCLINE-active against gram +ve, gram-
ve,anaerobes

32.  TIGEICYCLINE-active against gram +ve, gram-
ve,anaerobes
 Usual dose 100mg iv 1st dose than 50mg ivq12h.
 No dose adjustment required
 CLINDAMYCIN- usual dose=600mg-900mg(iv) q8h
150-300mg(po) q6h
 No dose adjustment required

33.  AZTERONAM- usual dose -1-2gm ivq 8h
 Crcl- 50-80ml/min-2gm(iv)q 8hr
 -10- 50 ivq8h-1 gm(iv)q 8 hr
< 10 -500q 8 hr
 MEROPENEM-usual dose-500-1gm iv q 8h
 Crcl-25-50ml/mint- 1gm iv q12h
 Crcl- 10-25ml/min- 500 mg iv q12h
 Crcl-<100ml/mint-500 mg iv q24
 ERTAPENEM- usual dose -1gm iv/imq 24h
 Crcl-30-80ml- no change
 Crcl< 30ml/mint- 500mg ivq24h

34.  IMIPENEM/CILASTATIN- usual dose-500mg-1gmq 6hr
 Crcl-50-80ml/m- 500 iv q 6hr
 Crcl -10-50ml/m- 500 iv q 8hr
 Crcl- <10ml/m-< 250 mg q 12h
 DORIPENEM-usual dose-500mg- 1gm iv q8h
 Crcl-25-50ml/m- 1gm iv 12hr
 Crcl-10-25 ml/m-500 mg iv 12 hr
 Amoxycillin/clavulanic acid- usal dose-1.2gm 6-8 hr
 Crcl-50-80ml/m- 500/125(po)q12 hr
 Crcl-10-50ml-500/125(po) q 24 hr

35.  Piperacillin/Tazobactum- usual dose-3.375 gm iv q 6 hr
 Crcl->40ml/m- no change
 Crcl-20-40ml/m- 2.25 gm iv q 6hr
 Crcl-<20ml/m-2.25 gm iv q 8hr
 Ceftriaxone-usual dose-1-2 gm iv
 No dose adjustment
 Ceftazidime- usual dose-2 gm iv q 8hr
 Crcl-50-80 ml (1gm)q 24 hr
 Crcl-< 10mg/ml- 500 iv q 24hr

36.  CEFOPERZONE- Normal dose 2gm iv 12 hr
 No dose adjustment
 CEFIXIME-usual dose- 400mg(po) q 12h
or200mg(po)q12
 Crcl-10-50ml-300mg(po) 24h
 Crcl- ‹ 10 ml/m-200 mg (po) 24 hr
 CEFOTAXIME- usual dose-2gm iv q 6hr
 Crcl-50-80ml/m- no change
 Crcl-10-50ml(1gm) iv q 6hr
 Crcl-<10-1gm iv q 12hr

37.  CEFUROXIME- usual dose-1.5gm(iv) q 8hr
 -500(po) q 12 hr
 Crcl-50-80-750mg iv12hr
 500mg(po)q12 hr
 Crcl-10-50-750(iv) q 24hr
-250 mg(po) 2 hr

38. TAKE HOME MESSAGE
 Keep Cr limitation in your sight.
 Take care of question your size and its limitation.
 Use appropriate body wt. and serum cretanine.
 Check different resources.
 Clinical consequences follow up.