Electrolytes Imbalance: A Rare Side Effect of Piperacillin ... of the College of Physicians and...
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Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 419-420 419 INTRODUCTION Piperacillin/tazobactam is a combination of semi- synthetic ureidopenicillin and β-lactamase inhibitor, with broad spectrum antimicrobial activity that is useful in treating polymicrobial and gram-negative bacterial infection. 1 It is mainly eliminated by glomerular filtration. There are reported cases which described electrolytes imbalance, 2 and other adverse effects with different antibiotics; 3-7 however, this is an unusual case of a rare but severe hypokalemia induced by piperacillin/ tazobactam in a postoperative patient who was treated for aspiration pneumonia. CASE REPORT A 76-year-old woman was admitted from Accidents and Emergency Department with a fractured neck of right femur and wound to her right ear after a fall. She had no significant past medical history apart from being suffering from anxiety for which she was taking chlorpromazine for the last 6 years. She did not have any drug allergy. She was independently mobile at home. On physical examination the patient was apyrexial (36.9 o C) with 93/minutes pulse, blood pressure of 173/86 mm/Hg, respiratory rate of 18/minutes and oxygen saturations of 97% on air. Her chest was clear on auscultation; abdomen was non distended, soft and non tender with positive bowel sounds. Right leg was shortened and internally rotated with right hip kept in flexed and abducted position. There was no neuro- vascular deficit. X-ray showed subtrochanteric fracture of the right femur. Her haemoglobin was 10.7 g/dL and white cell count was 13.8 x 10 3 with normal liver function test, urea and electrolytes. She was immediately resuscitated with 4 litres of intravenous (IV) normal saline within 48 hours and was taken to theatre for proximal femur nailing on the 3 rd day of her admission. On the 2 nd postoperative day she complained of nausea, vomiting and difficulty in breathing. On physical examination, pulse was 80/minutes, blood pressure of 96/70 mmHg, temperature of 37.7 o C and respiratory rate of 22/minutes with oxygen saturation of 93% on air. Chest examination revealed bilateral lower zone crepitations. Chest X-ray showed left lower lobe shadowing (consolidation). She was started on IV Tazocin 4.5 g (piperacillin 4 g, tazobactam 500 mg), 3 times a day for lower respiratory tract infection. This was done according to the hospital protocol after discussing her case with the micro- biologist. She had full blood count, liver function tests, urea and electrolytes checked every day. On the 1 st postoperative day, before starting piperacillin/ tazobactam, her serum potassium level was 4.2 mmol/l. On the 2 nd postoperative day, she was started on piperacillin/tazobactam therapy for chest infection. Within 24 hours after commencing piperacillin/ tazobactam therapy, her serum potassium level dropped to 3.6 mmol/l. Her progressive hypokalemia was treated with 80 mmol KCL in normal saline over 24 hours. Within 48 hours after commencing piperacillin/tazobactam therapy, her potassium level further dropped to 2.9 mmol/l and sodium level increased to 150 mmol/l with normal renal function. There was no apparent cause for her deteriorating hypokalemia and hypernatremia. At 72 hours of initiation of piperacillin/tazobactam therapy, her general condition deteriorated further and on urgent lab analyser, serum potassium level was 2.4 mmol/l and sodium was 158 mmol/l. Electrolytes changes summarised ABSTRACT Electrolytes imbalance has been reported with the use of several antimicrobials. We report a case of severe hypokalemia secondary to piperacillin/tazobactam in a patient with normal renal function and normal serum potassium level who had presented with a fractured neck of femur. The electrolytes abnormality was corrected once piperacillin/tazobactam was stopped. To our knowledge, this is the first case to describe an early severe hypokalemia induced by piperacillin/ tazobactam therapy in an otherwise healthy individual. Key words: Hypokalemia. Hypernatremia. Piperacillin/tazobactam. Electrolytes imbalance. Department of Trauma and Orthopaedics, The University Hospital Birmingham NHS Foundation Trust, United Kingdom. Correspondence: Dr. Shakir Hussain, 40, Painswick Road, Hallgreen, Birmingham, West Midlands, B28 OHF, United Kingdom. E-mail: [email protected] Received March 18, 2009; accepted February 23, 2010. Electrolytes Imbalance: A Rare Side Effect of Piperacillin/ Tazobactam Therapy Shakir Hussain, Shakir Syed and Khalid Baloch CASE REPORT
Transcript of Electrolytes Imbalance: A Rare Side Effect of Piperacillin ... of the College of Physicians and...
Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 419-420 419
INTRODUCTION
Piperacillin/tazobactam is a combination of semi-synthetic ureidopenicillin and β-lactamase inhibitor, withbroad spectrum antimicrobial activity that is useful intreating polymicrobial and gram-negative bacterialinfection.1 It is mainly eliminated by glomerular filtration.
There are reported cases which described electrolytesimbalance,2 and other adverse effects with differentantibiotics;3-7 however, this is an unusual case of a rarebut severe hypokalemia induced by piperacillin/tazobactam in a postoperative patient who was treatedfor aspiration pneumonia.
CASE REPORT
A 76-year-old woman was admitted from Accidents andEmergency Department with a fractured neck of rightfemur and wound to her right ear after a fall. She had nosignificant past medical history apart from beingsuffering from anxiety for which she was takingchlorpromazine for the last 6 years. She did not have anydrug allergy. She was independently mobile at home.
On physical examination the patient was apyrexial(36.9oC) with 93/minutes pulse, blood pressure of173/86 mm/Hg, respiratory rate of 18/minutes andoxygen saturations of 97% on air. Her chest was clearon auscultation; abdomen was non distended, soft andnon tender with positive bowel sounds. Right leg wasshortened and internally rotated with right hip kept inflexed and abducted position. There was no neuro-
vascular deficit. X-ray showed subtrochanteric fractureof the right femur. Her haemoglobin was 10.7 g/dL andwhite cell count was 13.8 x 103 with normal liver functiontest, urea and electrolytes.
She was immediately resuscitated with 4 litres ofintravenous (IV) normal saline within 48 hours and wastaken to theatre for proximal femur nailing on the 3rd dayof her admission. On the 2nd postoperative day shecomplained of nausea, vomiting and difficulty inbreathing. On physical examination, pulse was80/minutes, blood pressure of 96/70 mmHg, temperatureof 37.7oC and respiratory rate of 22/minutes with oxygensaturation of 93% on air. Chest examination revealedbilateral lower zone crepitations. Chest X-ray showedleft lower lobe shadowing (consolidation). She wasstarted on IV Tazocin 4.5 g (piperacillin 4 g, tazobactam500 mg), 3 times a day for lower respiratory tractinfection. This was done according to the hospitalprotocol after discussing her case with the micro-biologist. She had full blood count, liver function tests,urea and electrolytes checked every day. On the 1st
postoperative day, before starting piperacillin/tazobactam, her serum potassium level was 4.2 mmol/l.On the 2nd postoperative day, she was started onpiperacillin/tazobactam therapy for chest infection.Within 24 hours after commencing piperacillin/tazobactam therapy, her serum potassium level droppedto 3.6 mmol/l. Her progressive hypokalemia was treatedwith 80 mmol KCL in normal saline over 24 hours. Within48 hours after commencing piperacillin/tazobactamtherapy, her potassium level further dropped to 2.9mmol/l and sodium level increased to 150 mmol/l withnormal renal function. There was no apparent cause forher deteriorating hypokalemia and hypernatremia. At 72hours of initiation of piperacillin/tazobactam therapy, hergeneral condition deteriorated further and on urgent labanalyser, serum potassium level was 2.4 mmol/l andsodium was 158 mmol/l. Electrolytes changes summarised
ABSTRACTElectrolytes imbalance has been reported with the use of several antimicrobials. We report a case of severe hypokalemiasecondary to piperacillin/tazobactam in a patient with normal renal function and normal serum potassium level who hadpresented with a fractured neck of femur. The electrolytes abnormality was corrected once piperacillin/tazobactam wasstopped. To our knowledge, this is the first case to describe an early severe hypokalemia induced by piperacillin/tazobactam therapy in an otherwise healthy individual.
Key words: Hypokalemia. Hypernatremia. Piperacillin/tazobactam. Electrolytes imbalance.
Department of Trauma and Orthopaedics, The UniversityHospital Birmingham NHS Foundation Trust, United Kingdom.
Correspondence: Dr. Shakir Hussain, 40, Painswick Road,Hallgreen, Birmingham, West Midlands, B28 OHF, United Kingdom.E-mail: [email protected]
Received March 18, 2009; accepted February 23, 2010.
Electrolytes Imbalance: A Rare Side Effect of Piperacillin/Tazobactam Therapy
Shakir Hussain, Shakir Syed and Khalid Baloch
CASE REPORT
in Table I. The piperacillin/tazobactam therapy wasstopped and intravenous co-amoxiclav (amoxicillin withclavulanic acid) 1.2 g was started 3 times a day, to treather chest infection. Piperacillin/tazobactam was stoppedas it was felt that this was the most likely reason for thepatient’s deranged electrolytes. After 24 hours patient’sserum potassium level raised from 2.4 to 3.1 mmol/l andsodium dropped from 158 mmol/l to 149 mmol/l. On thesubsequent day potassium and sodium levels normalizedto 4.2 mmol/l and 139 mmol/l respectively. Oralpotassium was only given for 3 days after potassiumlevel reached 4.2 mmol/l and then it stayed within thenormal limits thereafter.
DISCUSSIONPiperacillin/tazobactam is used widely in patients of allage groups to treat various infections. Potassium andmagnesium losses are reported in patients withpiperacillin therapy8 on intensive care units with multipleco-morbidities including renal impairment. The adverseeffects reported with piperacillin/tazobactam therapyare; type-I hypersensitivity, acute delirium,3 neutropenia,4rash,5 delayed type hypersensitivity reaction andparesthesia.6,7 The authors could not find any reportedcases of hypokalemia occurring in patients treated withpiperacillin/tazobactam in other wise healthy patient withno renal impairment. Use of the Naranjo probabilityscale and the Drug Interaction Probability Scale (DIPS)indicated a probable relationship between hypokalemiaand the administration of piperacillin/tazobactam.9,10
Most of the adverse effects of piperacillin/tazobactamare associated with long-term therapy such as, delayedtype hypersensitivity, neutropenia or parasthesiae.Prolonged therapy with piperacillin/tazobactam rarelyresults in electrolytes imbalance in healthy individuals.However, patients with pre-existing renal impairment aremore prone to develop hypokalemia with piperacillin/tazobactam therapy.
In this patient, apart from treating with piperacillin/tazobactam, there was no obvious cause for the electrolyteimbalance. Following cessation of piperacillin/ tazo-bactam therapy the patient’s electrolytes returned tonormal and therefore, one could presume that thepiperacillin/tazobactam therapy was responsible for theelectrolyte imbalance. A secondary effect of piperacillin/tazobactam therapy is hypernatremia as was noted inthis patient. To conclude, hypokalemia is a known but uncommonadverse effect of piperacillin/tazobactam therapy. Thisreport describes the first case of severe hypokalemiainduced by piperacillin/tazobactam therapy in a patientwith normal renal function and normal potassium level.Serum sodium level should also be monitored in allpatients receiving piperacillin/tazobactam therapy. It issuggested to closely monitor electrolytes in patientstreated with piperacillin/tazobactam.
REFERENCES1. Perry CM, Markham A. Piperacillin/tazobactam: an updated
review of its use in the treatment of bacterial infections. Drugs1999; 57:805-43.
2. Zietse R, Zoutendijk R, Hoorn EJ. Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol2009; 5:193-202.
3. Tong MK, Siu YP, Yung CY, Kwan TH. Piperacillin/tazobactam-induced acute delirium in a peritoneal dialysis patient. NephrolDial Transplant 2004; 19:1341.
4. Peralta FG, Sanchez MB, Roiz MP, Pena MA, Tejero MA, ArjonaR. Incidence of neutropenia during treatment of bone-relatedinfections with piperacillin-tazobactam. Clin Infect Dis 2003;37:1568-72. Epub 2003 Oct 20.
5. LeClaire AC, Martin CA, Hoven AD. Rash associated withpiperacillin/tazobactam administration in infectious mononucleosis.Ann Pharmacother 2004; 38:996-8. Epub 2004 Apr 27.
6. Behbahani R, Kostman JR. Hypersensitivity reaction duringprolonged use of piperacillin/tazobactam in treatment ofosteomyelitis. Ann Pharmacother 1995; 29:936-7.
7. Lambourne J, Kitchen J, Hughes C, Merry C. Piperacillin/tazobactam-induced paresthesiae. Ann Pharmacother 2006;40:977-9. Epub 2006 18.
8. Polderman KH, Girbes AR. Piperacillin-induced magnesium and
potassium loss in intensive care unit patients. Intensive Care Med2002; 28:520-2. Epub 2002 Mar 15.
9. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA,et al. A method for estimating the probability of adverse drugreactions. Clin Pharmacol Ther 1981; 30:239-45.
10. Horn JR, Hansten PD, Chan LN. Proposal for a new tool toevaluate drug interaction cases. Ann Pharmacother 2007; 41:674-80. Epub 2007 Mar 27.
420 Journal of the College of Physicians and Surgeons Pakistan 2010, Vol. 20 (6): 419-420
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Table I: Laboratory test results.Parameters Admission 72 hours post- 3 days after Reference
antibiotic therapy cessation range Sodium (mmol/l) 140 158 139 135-145 Potassium (mmol/l) 4.8 2.4 4.2 3.5-5.0Urea (mmol/l) 6.7 3.7 3.6 2.5-6.7Creatinine 74 80 53 70-150LFT’s Normal Normal Normal ---Haemoglobin (g/dl) 10.4 8.8 9.5 13.5-18WBC count (x103) 15.9 13.5 2.4 4.0 – 11ESR (mm/h) 68 88 88 1-22CRP (mg/l) 244 86 105 0-10LFT’s = Liver function tests; WBC = White blood cell; ESR = Erythrocyte sedimentation rate;CRP = C-reactive protein.
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