- Email: [email protected]
ARILDONE, A POTENT INHIBITOR OF CYTOMEGALOVIRUS REPLICATION
1214
(total dose 2 -8g). On the 15th day profuse painful haematuria with strangury developed. Urine cultures were sterile and pain was alleviated only by narcotic analgesics. Dysuria and haematuria persisted for 2 weeks. Case 3.-A man aged 70 with myeloma received oral cyclophosphamide 100 to 150 mg daily, for 2 years. After a total dose of 72.5 g, haematuria and dysuria developed, and remitted 1 week after discontinuation of the drug. After 5 months of maintenance with melphalan, he again received oral cyclophosphamide, 3-22in 32 days, without incident. 4 months later, he received a single intravenous dose of 500 mg cyclophosphamide and 200 mg of carmustine. 5 weeks later, the carmustine was repeated, together with 30 mg doxorubicin. 3 weeks after this final course of cytotoxic drugs, dysuria and gross haematuria developed with clot retention requiring suprapubic cystotomy. Haematuria persisted, with intermittent improvements and exacerbations, requiring transfusion of 16 units of blood. Active haemorrhagic cystitis was present at his death 7 weeks later from a pulmonary embolus. Since his hospital admission and confinement to bed were due solely to cystitis, it must be considered a contributory cause of his death. Case 4.-A man aged 67 had had macroglobulinaemia for 9 years. Since diagnosis he had been treated intermittently with oral cyclophosphamide 50-150 mg daily. At the onset of cystitis, he had 8 been taking 100 mg daily for 54 weeks (total dose in this period 37 -8 in Haematuria and at first varied from g). began abruptly severity day to day, but after 1 week it became progressively worse and eventually so profuse that continuous manual bladder irrigation was necessary to remove the abundant clots. Inhibition of urokinase activity by oral administration of aminocaproic acid was without’ effect. The bladder volume was reduced to 110 ml and cystoscopy showed intense mucositis with vasodilatation and hundreds of
bleeding points. Intravesical application of dimethylsulphoxide did not reduce the haemorrhage. Instillation of 1% formalin (0’4% formaldehyde) for 10 min produced only transient reduction of haematuria. Fever and E coli bacteraemia developed as a result of repeated instrumentation and responded to antibiotic therapy but his general condition deteriorated. After instillation of 4% formalin (1 -6% formaldehyde) for 30 min, bleeding diminished immediately and resolved completely in 24 h. 1 week later he was discharged from hospital without urinary symptoms. The cystitis had lasted 4 weeks and 25 units of blood had been transfused. Development of a fibrotic, contracted bladder is a potential late complication in this patient. Studies in dogs3and necropsy findings in a child show that cystitis induced by cyclophosphamide is not confined to the mucosa.
Inflammation,
oedema,
vascular
engorgement,
haemorrhage, and fibrosis extend throughout the bladder wall to the serosa. Such extensive damage explains the often intractable nature of severe cases. Most patients who receive long-term low-dose cyclophosphamide remain free of cystitis, and we cannot discern a common risk factor in our four cases. Their ages, underlying of administration, and total drug doses varied. diseases, Potential risk factors (dehydration, oliguria, urinary obstruction, or retention) were not present. In cases 1 and 3., cystitis developed after discontinuation of cyclophosphamide and in case 3 carmustine and doxorubicin may have contributed to the injury ofa bladder already route
damaged by cyclophosphamide. It is uncertain whether regular monitoring for microscopic haematuria during treatment with cyclophosphamide might provide adequate warning of impending cystitis. When haemorrhagic cystitis from this drug is established and severe and conservative
measures
ARILDONE, A POTENT INHIBITOR OF CYTOMEGALOVIRUS REPLICATION
SIR,-The severity of disease caused by human cytomegalovirus (CMV) in the newborn and in immunocompromised patients, particularly after bone marrow transplantation, demands an effective antiviral agent. The escalation of cases of the acquired immunodeficiency syndrome (AIDS), in which CMV is an important opportunist pathogen if not directly connected with the aetiology, further reinforces the need for such a drug. No treatment is available, although various compounds have been investigated, including nucleoside analogues and interferons, singly or in combination. Arildone (WIN 38020), an aryl-&bgr;-diketone (4-[6-(2-chloro-4-methoxy) phenoxyl] hexyl-3, 5-heptanedione), has broad-spectrum activity against several important DNA and RNA viral pathogens.l Arildone is well tolerated in cellular and animal and there was no evidence of mutagenicity in experimental models standard tests.22 In our laboratory CMV is grown in human embryonic lung fibroblasts (MRCs cells). These cells were tested for growth in the presence of arildone. Cells were seeded at a rate which provided confluent monolayers after five days’ incubation and which required at least three mitotic cycles. Growth medium was supplemented with varying concentrations of arildone from a 1 mg/ml stock solution prepared in 100% dimethylsulphoxide (DMSO). Treatment with DMSO alone, in the final concentrations used, has no effect on cell growth (table). Monolayer formation rate, cell morphology, and viable cell numbers were unaffected by levels of arildone effective against CMV. At concentrations above 8 pglml there was some reduction in growth rate. The effect of arildone on CMV replication was determined by the yield-reduction method.3Cells were infected at multiples of five plaque-forming units per cell and maintained in medium supplemented with varying concentrations of arildone. Controls contained the equivalent concentration of DMSO alone. Infected monolayers were harvested at intervals after infection and progeny virus titres were determined by infective centre assays. The effects of arildone on the growth of West virus, a laboratory adapted isolate of CMV from a heart transplant recipient, are shown in the figure. The drug partly suppressed virus yield at 2 J.lg/ml but completely blocked virus production at 3 g/ml. Virus growth characteristics in the presence of 0’ 3% DMSO alone were similar to those with 1 pg/ml arildone or in cultures without either substance. When virus growth was completely prevented infected cells remained in the early stage of cell rounding with no signs of cytomegaly or development of typical DNA containing inclusions.We have observed similar effects of arildone on the growth of the prototype virus AD169 and on several low passage clinical isolates. Arildone inhibits poliovirus replication by preventing vinon uncoating,5and this novel mechanism may account for its broad spectrum of activity against viruses. Our preliminary studies (unpublished) indicate a similar early blockage in the CMV .,
1. Kim
KS, Sapienza VJ, Carp RI. Antiviral activity of arildone on deoxyribonucleic and ribonucleic acid viruses. Antimicrob Ag Chemother 1980; 18: 276-80. 2. McSharry JJ, Pancic F. Arildone: &bgr;-diketone. In: Came PE, Caliguiri LA, eds Chemotherapy of viral infections. (Handb Exp Pharmacol 61) Berlin SpringerVerlag, 1982: 419-44. 3. Tyms AS, Scamans EM, Naim HM. The in vitro activity of acyclovir and related compounds against cytomegalovirus infections. J Antimicrob Chemother 1981; 8: 65-72.
4. Tyms AS, Williamson JD. Inhibitors of polyamine biosynthesis block human cytomegalovirus replication Nature 1982; 297: 690-91 5. McSharry JJ, Caliguiri LA, Eggers MJ. Inhibition of uncoating of polivirus by arildone, a new antiviral drug. Virology 1979; 97: 307-15 EFFECT OF ARILDONE AND DMSO ON GROWTH OF
fail, the intravesical instillation of
formaldehyde may be lifesaving. Albany Medical College and VA Medical Center, Albany, NY 12208, USA 3.
ALEXANDER S. D. SPIERS GUNDHABHAKTHA CHIKKAPPA HARRY J. WILBUR
Philips FS, Sternberg SS, Cronin AP, Vidal PM. Cyclophosphamide bladder toxicity. Cancer Res 1961; 21: 1577-89.
MACSCELLS
’——————!———————n—————————————
and urinary
*Mean ±SD obtained from 6 cell
monolayers.
1215 SEVERE DEFICIENCY OF VITAMIN-K-DEPENDENT CLOTTING FACTORS K WAS STARTED,
(II, VII, IX, X) ON DAY 6, WHEN PARENTERAL VITAMIN
WITH CORRECTION OF DEFICIENCIES BY DAY
Effect of arildone
on
CMV
infectivity in MRCS cells.
replication cycle. We trying out arildone cream in genital herpes simplex infections, and the information that systemic administration has prevented death from poliovirus in an animal model6 suggests that this drug may be useful in treating CMV infection. We thank
Sterling Winthrop for supplying arildone.
Department of Medical Microbiology, St Mary’s Hospital Medical School,
D.J.JEFFRIES
London W2 1PG
A. S. TYMS
SEVERE DEPLETION OF VITAMIN-K-DEPENDENT CLOTTING FACTORS DURING POSTOPERATIVE LATAMOXEF THERAPY
SIR,-Gross depletion of the vitamin-K-dependent clotting shortly after major surgery is unusual, though vitamin K deficiency has been recorded in patients on intensive, and usually prolonged, antibiotic therapy.I,2 Prolonged prothrombin times in patients on latamoxef (moxalactam) have been recorded factors
occasionally but only in malnourished or debilitated patients. 3,4 We have observed gross derangement of haemostasis, first noted 84 h after major surgery and initiation of treatment with this antibiotic in a patient with peritonitis, the features being characteristic of severe depression of all the vitamin-K-dependent clotting factors. A 55-year-old woman with no history of diarrhoea, bleeding, or liver disease and not on medication was admitted to hospital with abdominal pain and shock subsequently diagnosed as due to peritonitis caused by perforation of the sigmoid colon. At operation (colectomy, colostomy, and peritoneal lavage with tetracycline) the liver appeared normal and there was no unusual bleeding. Latamoxef 2 g by intravenous injection was given during the operation and 8-hourly thereafter. 48 h after surgery, respiratory failure developed, and the patient was transferred to intensive care. There were no clinical haemorrhagic features, but prothrombin and partial thromboplastin times were prolonged (table), with gross deficiency of the vitamin-K-dependent factors II, VII, IX, and X, but raised levels of fibrinogen and factor VIII. Latamoxef was discontinued and 10 mg vitamin K was given daily by intravenous injection for 3 days, which totally corrected the
9
coagulation disorders. The patient was also on papaveretum, cloxacillin (started at the time of the first abnormal coagulation screen), cimetidine, dopamine and frusemide. The patient quickly recovered and was discharged. 1 month later she had multiple pulmonary emboli and was readmitted to hospital; her prothrombin time was normal and warfarin anticoagulation was achieved without difficulty. The coagulation disorder most often complicating major surgery, especially in the presence of sepsis and respiratory distress syndrome, is disseminated intravascular coagulation, in which platelet counts and fibrinogen, factor V, and factor VIII levels are low. This did not happen in our patient, who had severe deficiencies in the vitamin-K-dependent clotting factors. Preoperatively there was no history of predisposition to vitamin K deficiency, and major surgery was done without unusual bleeding. Acute liver damage sufficient to cause almost complete depletion of vitamin-Kdependent factors without depression of fibrinogen must be unusual, and liver function tests were normal, apart from a serum alkaline phosphatase of 200 units on admission (falling slowly to normal thereafter) and transient slight increase in y-glutamyltranspeptidase to 60 units on the third postoperative day. In this patient severe depression of vitamin-K-dependent clotting factors developed rapidly after surgery and quickly responded to vitamin K. The Committee on Safety of Medicines has lately drawn attention to the fact that latamoxef may induce prolongation of prothrombin time but notes that no case of haemorrhage has been reported in the short time that this antibiotic has been marketed in the UK.We cannot prove that latamoxef caused the gross disturbance of vitamin K metabolism observed. All we can say is that it happened, and was severe, in a patient taking an antibiotic that may prolong the prothrombin time. Monitoring of the coagulation status of patients on latamoxef after major surgery would seem prudent.
Departments of Anaesthetics, Surgery, Haematology, and Medicine, Aberdeen Royal Infirmary, Aberdeen AB9 2ZB
F. M. MACLENNAN A. K. AH-SEE A. EVAN WONG J. A. ANDERSON B. BENNETT
HYPOPROTHROMBINAEMIC BLEEDING ASSOCIATED WITH CEFTRIAXONE
SiR,-Reports on hypoprothrombinaemic bleeding in association third-generation cephalosporins and latamoxef (moxalactam) (Jan 29, p 250; March 5, p 535) prompt us to report a case attributable to ceftriaxone (’Rocephin’), a third-generation cephalosporin with high antibacterial activity and substantial with
6.
1. 2.
3.
McKinlay MA, Miralles JV, Brisson CJ, Pancic F. Prevention of human poliovirus induced paralysis and death in mice by the novel antiviral agent arildone. Antimicrob Ag Chemother 1982; 22: 1022-25. Hern JM. Hypoprothrombinaemia in patients undergoing prolonged intensive care. Med J Aust 1971; ii: 716. Pineo GF, Gallos AS, Hirsh J Unexpected vitamin K deficiency in hospitalized patients. Can Med Assoc J 1973; 109: 880-83. Bang NU, Tessler SS, Heidenreich RO, Marks CA, Mattler LE. Effects of moxalactam on blood coagulation and platelet function. Rev Infect Dis 1982; 4 (suppl):
elimination in the bile. A 29-year-old woman on chronic haemodialysis underwent cholecystectomy. Her preoperative ’Normotest’ result was 140%. Postoperatively the patient was given an adjusted dose of 1 g
S546-S554. 4. Pakter RL, Russell TR, Mielke
CH, West D. moxalactam. JAMA 1982; 248: 1100.
Coagulopathy associated with the use of
5. Committee
on Safety of Medicine. Bleeding (moxalactam). Curr Problems 1983, no 10.
diatheses with antibiotics—latamoxef
(total dose 2 -8g). On the 15th day profuse painful haematuria with strangury developed. Urine cultures were sterile and pain was alleviated only by narcotic analgesics. Dysuria and haematuria persisted for 2 weeks. Case 3.-A man aged 70 with myeloma received oral cyclophosphamide 100 to 150 mg daily, for 2 years. After a total dose of 72.5 g, haematuria and dysuria developed, and remitted 1 week after discontinuation of the drug. After 5 months of maintenance with melphalan, he again received oral cyclophosphamide, 3-22in 32 days, without incident. 4 months later, he received a single intravenous dose of 500 mg cyclophosphamide and 200 mg of carmustine. 5 weeks later, the carmustine was repeated, together with 30 mg doxorubicin. 3 weeks after this final course of cytotoxic drugs, dysuria and gross haematuria developed with clot retention requiring suprapubic cystotomy. Haematuria persisted, with intermittent improvements and exacerbations, requiring transfusion of 16 units of blood. Active haemorrhagic cystitis was present at his death 7 weeks later from a pulmonary embolus. Since his hospital admission and confinement to bed were due solely to cystitis, it must be considered a contributory cause of his death. Case 4.-A man aged 67 had had macroglobulinaemia for 9 years. Since diagnosis he had been treated intermittently with oral cyclophosphamide 50-150 mg daily. At the onset of cystitis, he had 8 been taking 100 mg daily for 54 weeks (total dose in this period 37 -8 in Haematuria and at first varied from g). began abruptly severity day to day, but after 1 week it became progressively worse and eventually so profuse that continuous manual bladder irrigation was necessary to remove the abundant clots. Inhibition of urokinase activity by oral administration of aminocaproic acid was without’ effect. The bladder volume was reduced to 110 ml and cystoscopy showed intense mucositis with vasodilatation and hundreds of
bleeding points. Intravesical application of dimethylsulphoxide did not reduce the haemorrhage. Instillation of 1% formalin (0’4% formaldehyde) for 10 min produced only transient reduction of haematuria. Fever and E coli bacteraemia developed as a result of repeated instrumentation and responded to antibiotic therapy but his general condition deteriorated. After instillation of 4% formalin (1 -6% formaldehyde) for 30 min, bleeding diminished immediately and resolved completely in 24 h. 1 week later he was discharged from hospital without urinary symptoms. The cystitis had lasted 4 weeks and 25 units of blood had been transfused. Development of a fibrotic, contracted bladder is a potential late complication in this patient. Studies in dogs3and necropsy findings in a child show that cystitis induced by cyclophosphamide is not confined to the mucosa.
Inflammation,
oedema,
vascular
engorgement,
haemorrhage, and fibrosis extend throughout the bladder wall to the serosa. Such extensive damage explains the often intractable nature of severe cases. Most patients who receive long-term low-dose cyclophosphamide remain free of cystitis, and we cannot discern a common risk factor in our four cases. Their ages, underlying of administration, and total drug doses varied. diseases, Potential risk factors (dehydration, oliguria, urinary obstruction, or retention) were not present. In cases 1 and 3., cystitis developed after discontinuation of cyclophosphamide and in case 3 carmustine and doxorubicin may have contributed to the injury ofa bladder already route
damaged by cyclophosphamide. It is uncertain whether regular monitoring for microscopic haematuria during treatment with cyclophosphamide might provide adequate warning of impending cystitis. When haemorrhagic cystitis from this drug is established and severe and conservative
measures
ARILDONE, A POTENT INHIBITOR OF CYTOMEGALOVIRUS REPLICATION
SIR,-The severity of disease caused by human cytomegalovirus (CMV) in the newborn and in immunocompromised patients, particularly after bone marrow transplantation, demands an effective antiviral agent. The escalation of cases of the acquired immunodeficiency syndrome (AIDS), in which CMV is an important opportunist pathogen if not directly connected with the aetiology, further reinforces the need for such a drug. No treatment is available, although various compounds have been investigated, including nucleoside analogues and interferons, singly or in combination. Arildone (WIN 38020), an aryl-&bgr;-diketone (4-[6-(2-chloro-4-methoxy) phenoxyl] hexyl-3, 5-heptanedione), has broad-spectrum activity against several important DNA and RNA viral pathogens.l Arildone is well tolerated in cellular and animal and there was no evidence of mutagenicity in experimental models standard tests.22 In our laboratory CMV is grown in human embryonic lung fibroblasts (MRCs cells). These cells were tested for growth in the presence of arildone. Cells were seeded at a rate which provided confluent monolayers after five days’ incubation and which required at least three mitotic cycles. Growth medium was supplemented with varying concentrations of arildone from a 1 mg/ml stock solution prepared in 100% dimethylsulphoxide (DMSO). Treatment with DMSO alone, in the final concentrations used, has no effect on cell growth (table). Monolayer formation rate, cell morphology, and viable cell numbers were unaffected by levels of arildone effective against CMV. At concentrations above 8 pglml there was some reduction in growth rate. The effect of arildone on CMV replication was determined by the yield-reduction method.3Cells were infected at multiples of five plaque-forming units per cell and maintained in medium supplemented with varying concentrations of arildone. Controls contained the equivalent concentration of DMSO alone. Infected monolayers were harvested at intervals after infection and progeny virus titres were determined by infective centre assays. The effects of arildone on the growth of West virus, a laboratory adapted isolate of CMV from a heart transplant recipient, are shown in the figure. The drug partly suppressed virus yield at 2 J.lg/ml but completely blocked virus production at 3 g/ml. Virus growth characteristics in the presence of 0’ 3% DMSO alone were similar to those with 1 pg/ml arildone or in cultures without either substance. When virus growth was completely prevented infected cells remained in the early stage of cell rounding with no signs of cytomegaly or development of typical DNA containing inclusions.We have observed similar effects of arildone on the growth of the prototype virus AD169 and on several low passage clinical isolates. Arildone inhibits poliovirus replication by preventing vinon uncoating,5and this novel mechanism may account for its broad spectrum of activity against viruses. Our preliminary studies (unpublished) indicate a similar early blockage in the CMV .,
1. Kim
KS, Sapienza VJ, Carp RI. Antiviral activity of arildone on deoxyribonucleic and ribonucleic acid viruses. Antimicrob Ag Chemother 1980; 18: 276-80. 2. McSharry JJ, Pancic F. Arildone: &bgr;-diketone. In: Came PE, Caliguiri LA, eds Chemotherapy of viral infections. (Handb Exp Pharmacol 61) Berlin SpringerVerlag, 1982: 419-44. 3. Tyms AS, Scamans EM, Naim HM. The in vitro activity of acyclovir and related compounds against cytomegalovirus infections. J Antimicrob Chemother 1981; 8: 65-72.
4. Tyms AS, Williamson JD. Inhibitors of polyamine biosynthesis block human cytomegalovirus replication Nature 1982; 297: 690-91 5. McSharry JJ, Caliguiri LA, Eggers MJ. Inhibition of uncoating of polivirus by arildone, a new antiviral drug. Virology 1979; 97: 307-15 EFFECT OF ARILDONE AND DMSO ON GROWTH OF
fail, the intravesical instillation of
formaldehyde may be lifesaving. Albany Medical College and VA Medical Center, Albany, NY 12208, USA 3.
ALEXANDER S. D. SPIERS GUNDHABHAKTHA CHIKKAPPA HARRY J. WILBUR
Philips FS, Sternberg SS, Cronin AP, Vidal PM. Cyclophosphamide bladder toxicity. Cancer Res 1961; 21: 1577-89.
MACSCELLS
’——————!———————n—————————————
and urinary
*Mean ±SD obtained from 6 cell
monolayers.
1215 SEVERE DEFICIENCY OF VITAMIN-K-DEPENDENT CLOTTING FACTORS K WAS STARTED,
(II, VII, IX, X) ON DAY 6, WHEN PARENTERAL VITAMIN
WITH CORRECTION OF DEFICIENCIES BY DAY
Effect of arildone
on
CMV
infectivity in MRCS cells.
replication cycle. We trying out arildone cream in genital herpes simplex infections, and the information that systemic administration has prevented death from poliovirus in an animal model6 suggests that this drug may be useful in treating CMV infection. We thank
Sterling Winthrop for supplying arildone.
Department of Medical Microbiology, St Mary’s Hospital Medical School,
D.J.JEFFRIES
London W2 1PG
A. S. TYMS
SEVERE DEPLETION OF VITAMIN-K-DEPENDENT CLOTTING FACTORS DURING POSTOPERATIVE LATAMOXEF THERAPY
SIR,-Gross depletion of the vitamin-K-dependent clotting shortly after major surgery is unusual, though vitamin K deficiency has been recorded in patients on intensive, and usually prolonged, antibiotic therapy.I,2 Prolonged prothrombin times in patients on latamoxef (moxalactam) have been recorded factors
occasionally but only in malnourished or debilitated patients. 3,4 We have observed gross derangement of haemostasis, first noted 84 h after major surgery and initiation of treatment with this antibiotic in a patient with peritonitis, the features being characteristic of severe depression of all the vitamin-K-dependent clotting factors. A 55-year-old woman with no history of diarrhoea, bleeding, or liver disease and not on medication was admitted to hospital with abdominal pain and shock subsequently diagnosed as due to peritonitis caused by perforation of the sigmoid colon. At operation (colectomy, colostomy, and peritoneal lavage with tetracycline) the liver appeared normal and there was no unusual bleeding. Latamoxef 2 g by intravenous injection was given during the operation and 8-hourly thereafter. 48 h after surgery, respiratory failure developed, and the patient was transferred to intensive care. There were no clinical haemorrhagic features, but prothrombin and partial thromboplastin times were prolonged (table), with gross deficiency of the vitamin-K-dependent factors II, VII, IX, and X, but raised levels of fibrinogen and factor VIII. Latamoxef was discontinued and 10 mg vitamin K was given daily by intravenous injection for 3 days, which totally corrected the
9
coagulation disorders. The patient was also on papaveretum, cloxacillin (started at the time of the first abnormal coagulation screen), cimetidine, dopamine and frusemide. The patient quickly recovered and was discharged. 1 month later she had multiple pulmonary emboli and was readmitted to hospital; her prothrombin time was normal and warfarin anticoagulation was achieved without difficulty. The coagulation disorder most often complicating major surgery, especially in the presence of sepsis and respiratory distress syndrome, is disseminated intravascular coagulation, in which platelet counts and fibrinogen, factor V, and factor VIII levels are low. This did not happen in our patient, who had severe deficiencies in the vitamin-K-dependent clotting factors. Preoperatively there was no history of predisposition to vitamin K deficiency, and major surgery was done without unusual bleeding. Acute liver damage sufficient to cause almost complete depletion of vitamin-Kdependent factors without depression of fibrinogen must be unusual, and liver function tests were normal, apart from a serum alkaline phosphatase of 200 units on admission (falling slowly to normal thereafter) and transient slight increase in y-glutamyltranspeptidase to 60 units on the third postoperative day. In this patient severe depression of vitamin-K-dependent clotting factors developed rapidly after surgery and quickly responded to vitamin K. The Committee on Safety of Medicines has lately drawn attention to the fact that latamoxef may induce prolongation of prothrombin time but notes that no case of haemorrhage has been reported in the short time that this antibiotic has been marketed in the UK.We cannot prove that latamoxef caused the gross disturbance of vitamin K metabolism observed. All we can say is that it happened, and was severe, in a patient taking an antibiotic that may prolong the prothrombin time. Monitoring of the coagulation status of patients on latamoxef after major surgery would seem prudent.
Departments of Anaesthetics, Surgery, Haematology, and Medicine, Aberdeen Royal Infirmary, Aberdeen AB9 2ZB
F. M. MACLENNAN A. K. AH-SEE A. EVAN WONG J. A. ANDERSON B. BENNETT
HYPOPROTHROMBINAEMIC BLEEDING ASSOCIATED WITH CEFTRIAXONE
SiR,-Reports on hypoprothrombinaemic bleeding in association third-generation cephalosporins and latamoxef (moxalactam) (Jan 29, p 250; March 5, p 535) prompt us to report a case attributable to ceftriaxone (’Rocephin’), a third-generation cephalosporin with high antibacterial activity and substantial with
6.
1. 2.
3.
McKinlay MA, Miralles JV, Brisson CJ, Pancic F. Prevention of human poliovirus induced paralysis and death in mice by the novel antiviral agent arildone. Antimicrob Ag Chemother 1982; 22: 1022-25. Hern JM. Hypoprothrombinaemia in patients undergoing prolonged intensive care. Med J Aust 1971; ii: 716. Pineo GF, Gallos AS, Hirsh J Unexpected vitamin K deficiency in hospitalized patients. Can Med Assoc J 1973; 109: 880-83. Bang NU, Tessler SS, Heidenreich RO, Marks CA, Mattler LE. Effects of moxalactam on blood coagulation and platelet function. Rev Infect Dis 1982; 4 (suppl):
elimination in the bile. A 29-year-old woman on chronic haemodialysis underwent cholecystectomy. Her preoperative ’Normotest’ result was 140%. Postoperatively the patient was given an adjusted dose of 1 g
S546-S554. 4. Pakter RL, Russell TR, Mielke
CH, West D. moxalactam. JAMA 1982; 248: 1100.
Coagulopathy associated with the use of
5. Committee
on Safety of Medicine. Bleeding (moxalactam). Curr Problems 1983, no 10.
diatheses with antibiotics—latamoxef