Aust. ~-~ N.Z. J Med (1979), 9, pp. 69-70 _ _ -~ ~
CASE REPORT
Abdominal Pain Following Intravenous Benzyl Penicillin Administration P. C. Robinson*, T. W. Steelet. P. T. Jolleyi and D. 6.Frewin""
From the Royal Adelaide Hospital and the Institute of Medical and Veterinary Science, Adelaide
Summary: Abdominal pain following intravenous benzyl penicillin administration. P. C. Robinson, T W. Steele, P T Jolley and D B. Frewin, Aust. N.Z. J. Med.. 1979, 9, pp. 64-70.
The occurrence of abdominal pain (in three patients) a n d lower chest pain (in one patient) either during or immediately after the intravenous administration of high doses of benzyl penicillin is reported. All four patients were diagnosed as having bacterial endocarditis and had been receiving between 8 and 18 mega units of the drug per day for 2-3 weeks, w h e n the symptoms were first noticed A skin rash also appeared in each case, at this time. B o t h the rash and abdominal pain disappeared w h e n an alternative antibiotic was substituted for the penicillin.
Abdominal pain' is an unusual adverse reaction to benzyl penicillin administered intravenously. There has been a limited number of reports of this problem in the literature.', Therefore, we were interested to note, over a three-month period, that four patients receiving bolus intravenous injections of benzyl penicillin developed abdominal or chest pain while the drug was being administered. The present paper describes these four cascs which were reported to the Adverse Drug Reactions Monitoring Programme of the Royal Adelaide Hospital. Case Records
(1) A 19-year-old male presented with a 10-day history of rigors, headache and general malaise. His past history included repair of a coarctation of the aorta when aged live years. aortic valvotomy at age six and aortic valve replacement aged 18. On this admission a clinical diagnosis of .
~
"Resident Medical Officer, Royal Adelaide Hospital tSenior Director, Division of Clinical Microbiology, I MVS :Adverse Drug Reactions Officer, Royal Adelaide Hospital *'Senior Visiting Pharmacologist, Royal Adelaide Hospital. Correspondence Dr D 6. Frewin. Department of H u m a n Physiology a n d
Pharmacology, University of Adelaide. SA 5000 Accepted for publication. 24 July, 1978
bacterial endocarditis was confirmed by positive hlood cultures of Sr[cph!.loc.oc.c.u.r~ i u v ~ wsensitive s to peiiicillin. The patient was treated with intravenous benzyl penicillin 2 x 10" units six-hourly for 24 hours and then 3 x 10' units fourhourly for three weeks with probenecid 500 mg qid. Some 17 days aftcr beginning treatment with penicillin. he developed severe epigastric discomfort during administration of each dose. This ceased mhcn the ben7yl penicillin mas replaced by intravenous ccph:izolin 2 g eight-hourly. The patient also developed a fine. itchy. macular rash three days after the abdominal pain commenced and while still on the bewyl penicillin. The rash continued to spread during cephazolin therapy. Cephazolin was discontinued after two days and oral erythromycin 250 mg siu-hourly was substituted. The rash resolved Lvhilc the patient was on this antibiotic. (2) A 61-year-old man with a cardiac prosthesis developed symptoms of headache. f e w , chills and anorexia. A blood culture performed at thc time showed growth of Strc>ptococ.cus viriduns and the patient was treated with intravenous bcnzyl penicillin 3 x 10' units six-hourly for threeweeks. He responded after one week oftherapy and wab afebrilc and fell well Tor two weeks. when fever recurred. The onset of fever coincided with thrombophlebitis and cellulitis in the area of a rccent intravellous cannula. At this time he was admitted to the Royal Adelaide Hospital and bcnzyl penicillin was continued as a bolus intravenous injection. Severe upper abdominal pain of short duration ( I 3 mins) and facial itching were noted either during or immediately after each injection. The following day cloxiacillin was substituted for penicillin due to suspected .StuIJIf?,I"c"(.'.[~.s uuveur infection. Ahdominal pain did not occur with cloxacillin but the facial itching persisted. An urticaria1 rash appeared after four days. Ccphazolin was then substituted for cloxacillin. and the rash subsided.
(3) A 42-year-old man with a past history of rhcutnatic fever presented with a 4- 6-week story of generalised aches and pains. headaches and episodes of profuse sweating. A clinical diagnosis of bacterial endocarditis was confirmed by blood culture growth of Streptocorcus riridms. The patient was treated with intravenous benlyl penicillin 2 x 10" units qid for weeks with concurrent probcnccid'S00 mg qid, at which time abdominal pain (during penicillin administration) and a rash developed. The penicillin was replaced by intravenous vancomycin 500 mg six-hourly. Abdominal pain did not occur and the rash resolved.
3
(4) A 47-year-old woman with a mitral valve prosthesis presented with a three-month history of lethargy, anorexia, meight loss, nausea, night sweats and chills. Finger clubbing was noted as well as one splinter hacmorrhage, several peripheral skin lesions and splenomegaly. Several hlood cultures grew diphtheroids. Treatment with intravenous beniyl penicillin 2 x lo6 units four-hourly and inlravenous gentamicin 80 mg eight-hourly was begun. Three weeks later,
I0
ROBINSON E.T AL.
after a good clinical response. the onset or lower anterior chest pain was noted during intravenous penicillin injection. The pain lasted from one to three minutes and was minimal when the drug was given slowly. A somewhat atypical drug rash appeared four days later and was associated with mild fever and leueopenia. All these findings subsided when the penicillin was discontinued. Discussion
A common factor in the four cases presented in this report and in the case described previously by Davies ct ul.' was the clinical diagnosis of bacterial endocarditis. High doses of benzyl penicillin were administered to our patients and ranged from 8~ 18 mega-units per day for 2-3 weeks. All patients experienced the abdominal pain (Cases 1 , 2 and 3) or chest pain (Case 4) during or immediately after the intravenous administration of the penicillin. Giving the drug slowly, e.g. over 5- 10 mins, delayed the onset of pain in Case 3 and virtually eliminated it in Case 4. The rash which developed in the first three patients appeared to be a typical allergic type of rash, but that observed in Case 4 was somewhat less typical. The aetiology of the pain associated with intravenous penicillin administration is unclear.
VOI.. 9,
NO.
1
Davies et al.' suggest that it may be a doserelated phenomenon and our observations would support this view. However, the reason why abdominal or chest pain only occurred two or three weeks after the start of treatment remains unexplained, since the penicillin was given as an intravenous bolus injection every time. Additionally, the majority of patients developed a rash within four days of the onset of pain. Intestinal iIeus2 was not specifically excluded in these patients. In three cases, substitution of penicillin by an alternative antibiotic resulted in the disappearance of symptoms. Acknowledgements
We are grateful to the Medical Superintendent of the Royal Adelaide Hospital for allowing us to publish the respective case histories and to Mrs. K. James for expert secretarial assistance. Thc Adverse Drug Reactions Monitoring Programme at the Royal Adelaide Hospital is supported by a grant from the Commissioners of Charitable Funds. References Kr.( l n b . A. and BE\SI:II , h McK. ( 1 9 1 5 ~ :Thc u x of anritnotics, Heincmann. p. 21 2 DAVIPS.G. K.. T ~ JR \I XP, and SPI.UCLK. R T 119741: Abdominal pain dftcr I
in:ravcnous henzy! penicillin. /.mice1 2. 167. 3 RLPOKT [IF SUSPI-~IIII ADVI'RSL Unr (i R~-A?TI(IM Yo. 4 (197X): Aust. G0i.L. Puhlishing Service. Canberra.
CASE REPORT
Abdominal Pain Following Intravenous Benzyl Penicillin Administration P. C. Robinson*, T. W. Steelet. P. T. Jolleyi and D. 6.Frewin""
From the Royal Adelaide Hospital and the Institute of Medical and Veterinary Science, Adelaide
Summary: Abdominal pain following intravenous benzyl penicillin administration. P. C. Robinson, T W. Steele, P T Jolley and D B. Frewin, Aust. N.Z. J. Med.. 1979, 9, pp. 64-70.
The occurrence of abdominal pain (in three patients) a n d lower chest pain (in one patient) either during or immediately after the intravenous administration of high doses of benzyl penicillin is reported. All four patients were diagnosed as having bacterial endocarditis and had been receiving between 8 and 18 mega units of the drug per day for 2-3 weeks, w h e n the symptoms were first noticed A skin rash also appeared in each case, at this time. B o t h the rash and abdominal pain disappeared w h e n an alternative antibiotic was substituted for the penicillin.
Abdominal pain' is an unusual adverse reaction to benzyl penicillin administered intravenously. There has been a limited number of reports of this problem in the literature.', Therefore, we were interested to note, over a three-month period, that four patients receiving bolus intravenous injections of benzyl penicillin developed abdominal or chest pain while the drug was being administered. The present paper describes these four cascs which were reported to the Adverse Drug Reactions Monitoring Programme of the Royal Adelaide Hospital. Case Records
(1) A 19-year-old male presented with a 10-day history of rigors, headache and general malaise. His past history included repair of a coarctation of the aorta when aged live years. aortic valvotomy at age six and aortic valve replacement aged 18. On this admission a clinical diagnosis of .
~
"Resident Medical Officer, Royal Adelaide Hospital tSenior Director, Division of Clinical Microbiology, I MVS :Adverse Drug Reactions Officer, Royal Adelaide Hospital *'Senior Visiting Pharmacologist, Royal Adelaide Hospital. Correspondence Dr D 6. Frewin. Department of H u m a n Physiology a n d
Pharmacology, University of Adelaide. SA 5000 Accepted for publication. 24 July, 1978
bacterial endocarditis was confirmed by positive hlood cultures of Sr[cph!.loc.oc.c.u.r~ i u v ~ wsensitive s to peiiicillin. The patient was treated with intravenous benzyl penicillin 2 x 10" units six-hourly for 24 hours and then 3 x 10' units fourhourly for three weeks with probenecid 500 mg qid. Some 17 days aftcr beginning treatment with penicillin. he developed severe epigastric discomfort during administration of each dose. This ceased mhcn the ben7yl penicillin mas replaced by intravenous ccph:izolin 2 g eight-hourly. The patient also developed a fine. itchy. macular rash three days after the abdominal pain commenced and while still on the bewyl penicillin. The rash continued to spread during cephazolin therapy. Cephazolin was discontinued after two days and oral erythromycin 250 mg siu-hourly was substituted. The rash resolved Lvhilc the patient was on this antibiotic. (2) A 61-year-old man with a cardiac prosthesis developed symptoms of headache. f e w , chills and anorexia. A blood culture performed at thc time showed growth of Strc>ptococ.cus viriduns and the patient was treated with intravenous bcnzyl penicillin 3 x 10' units six-hourly for threeweeks. He responded after one week oftherapy and wab afebrilc and fell well Tor two weeks. when fever recurred. The onset of fever coincided with thrombophlebitis and cellulitis in the area of a rccent intravellous cannula. At this time he was admitted to the Royal Adelaide Hospital and bcnzyl penicillin was continued as a bolus intravenous injection. Severe upper abdominal pain of short duration ( I 3 mins) and facial itching were noted either during or immediately after each injection. The following day cloxiacillin was substituted for penicillin due to suspected .StuIJIf?,I"c"(.'.[~.s uuveur infection. Ahdominal pain did not occur with cloxacillin but the facial itching persisted. An urticaria1 rash appeared after four days. Ccphazolin was then substituted for cloxacillin. and the rash subsided.
(3) A 42-year-old man with a past history of rhcutnatic fever presented with a 4- 6-week story of generalised aches and pains. headaches and episodes of profuse sweating. A clinical diagnosis of bacterial endocarditis was confirmed by blood culture growth of Streptocorcus riridms. The patient was treated with intravenous benlyl penicillin 2 x 10" units qid for weeks with concurrent probcnccid'S00 mg qid, at which time abdominal pain (during penicillin administration) and a rash developed. The penicillin was replaced by intravenous vancomycin 500 mg six-hourly. Abdominal pain did not occur and the rash resolved.
3
(4) A 47-year-old woman with a mitral valve prosthesis presented with a three-month history of lethargy, anorexia, meight loss, nausea, night sweats and chills. Finger clubbing was noted as well as one splinter hacmorrhage, several peripheral skin lesions and splenomegaly. Several hlood cultures grew diphtheroids. Treatment with intravenous beniyl penicillin 2 x lo6 units four-hourly and inlravenous gentamicin 80 mg eight-hourly was begun. Three weeks later,
I0
ROBINSON E.T AL.
after a good clinical response. the onset or lower anterior chest pain was noted during intravenous penicillin injection. The pain lasted from one to three minutes and was minimal when the drug was given slowly. A somewhat atypical drug rash appeared four days later and was associated with mild fever and leueopenia. All these findings subsided when the penicillin was discontinued. Discussion
A common factor in the four cases presented in this report and in the case described previously by Davies ct ul.' was the clinical diagnosis of bacterial endocarditis. High doses of benzyl penicillin were administered to our patients and ranged from 8~ 18 mega-units per day for 2-3 weeks. All patients experienced the abdominal pain (Cases 1 , 2 and 3) or chest pain (Case 4) during or immediately after the intravenous administration of the penicillin. Giving the drug slowly, e.g. over 5- 10 mins, delayed the onset of pain in Case 3 and virtually eliminated it in Case 4. The rash which developed in the first three patients appeared to be a typical allergic type of rash, but that observed in Case 4 was somewhat less typical. The aetiology of the pain associated with intravenous penicillin administration is unclear.
VOI.. 9,
NO.
1
Davies et al.' suggest that it may be a doserelated phenomenon and our observations would support this view. However, the reason why abdominal or chest pain only occurred two or three weeks after the start of treatment remains unexplained, since the penicillin was given as an intravenous bolus injection every time. Additionally, the majority of patients developed a rash within four days of the onset of pain. Intestinal iIeus2 was not specifically excluded in these patients. In three cases, substitution of penicillin by an alternative antibiotic resulted in the disappearance of symptoms. Acknowledgements
We are grateful to the Medical Superintendent of the Royal Adelaide Hospital for allowing us to publish the respective case histories and to Mrs. K. James for expert secretarial assistance. Thc Adverse Drug Reactions Monitoring Programme at the Royal Adelaide Hospital is supported by a grant from the Commissioners of Charitable Funds. References Kr.( l n b . A. and BE\SI:II , h McK. ( 1 9 1 5 ~ :Thc u x of anritnotics, Heincmann. p. 21 2 DAVIPS.G. K.. T ~ JR \I XP, and SPI.UCLK. R T 119741: Abdominal pain dftcr I
in:ravcnous henzy! penicillin. /.mice1 2. 167. 3 RLPOKT [IF SUSPI-~IIII ADVI'RSL Unr (i R~-A?TI(IM Yo. 4 (197X): Aust. G0i.L. Puhlishing Service. Canberra.
