- Email: [email protected]
Aminoglycosides: single or multiple daily dosing?
1152
THE LANCET
creatinine clearance, immunoreactive endothelin concentrations in plasma, blood pressure, and heart rate (measured automatically) in 30 patients with stones in the kidney, and in 19 patients with ureteric
improved efficacy or decreased toxicity. It is important to emphasise that most patients were evaluated unblinded (fourteen of sixteen studies were open and two were double-blind) and treated
stones.
with concomitant antibiotics. Crucial to the choice between the two regimens is whether one is prepared to run a risk of 28% of not detecting an increase in nephrotoxicity of 10% if the single-dose regimen is chosen. Although comparison of Prins and colleagues’ results with our meta-analysis shows that the results on efficacy and ototoxicity are much the same, we disagree about the possible beneficial effect on nephrotoxicity of the single-dose treatment.
One day after ESWL, 24 h urinary albumin excretion was increased by 125 (6) mg (p < 0-01 vs before ESWL) in patients with renal sones, and by 72 (3) mg in patients with ureteric stones (p < 0-05 vs before ESWL, p < 0-01 vs patients with renal stones). Although pre-existing impairment of kidney function improved in most patients between two and five weeks after ESWL, creatinine clearance measured on the day after ESWL showed an increase in patients with reduced renal function (creatinine clearance < 80 mL/min) by 12% in those with renal stones, but only by 3% in patients with ureteric stones (p <: 005). Immediately after ESWL, patients with renal stones had higher plasma concentrations of immunoreactive endothelin than those with ureteric stones (4-1 [0.2] vs 3-7 [0’4] pg/mL, p<0-05). This endothelium-derived vasoconstrictor hormone mediates, among other effects, a reduction in glomerular filtration rate. Thereafter, as well as before ESWL, endothelin concentrations were not different. Compared with before ESWL, mean arterial blood pressure in patients with renal stones increased by 8 [3] mm Hg between two and five weeks after ESWL (p < 001), and fell by 4 [2] mm Hg in those with ureteric
(p < 0-05). Although ESWL
stones
is non-invasive, these results suggest that moderate mechanical damage of kidney tissue may lead, at least in some patients, to a temporary impairment of renal function and an increase in mean arterial blood pressure, which is more pronounced if stones are close to, or in, the kidney. THOMAS HAAK Centre of Internal Medicine and Department of Urology,
University Hospital,
ECKART JUNGMANN DIETGER JONAS
6000 Frankfurt 70, Germany
KLAUS HENNING USADEL
S, Fair W, et al. Report of the United States cooperative study of extracorporeal shockwave lithotripsy. J Urol 1986; 135: 1127-33. 2. Karlsen SJ, Smevik B, Hovig T. Acute morphological changes in kidney function following extracorporeal shock wave lithotripsy for renal stones. Br J Urol 1991; 76: 1. Drach GW, Dretler
241-45. 3. Ackaert KSJW, Schroder FH. Effects of extracorporeal shock wave lithotripsy (ESWL) on renal tissue. Urol Res 1989; 17: 3-7. 4. Kaude JV, Williams CM, Millner MR, Scott KN, Finlayson B. Renal morphology and function immediately after extracorporeal shock-wave lithotripsy. Am J Radiol 1985; 145: 305-13.
Aminoglycosides: single or multiple daily dosing? SIR,-Dr Prins and colleagues conclude (Feb 6, p 335) that a once daily dosing regimen of gentamicin is at least as effective as and less nephrotoxic than more frequent dosing. To establish the best aminoglycoside regimen, we extracted data for efficacy, nephrotoxicity, and ototoxicity from sixteeen randomised trials of more than 1000 patients and showed that the cure rate of the single-dose regimen was 82-2% compared with 81-6% for the multiple-dose regimen; the ototoxicity rate was 3-0% compared with 4-1%, and the rate of nephrotoxicity was 8-6% in each group.
Although these differences are small and not significant, the results do not exclude the possibility of missing a real difference in the meta-analysis (type II error). For example, the risk of not detecting that multiple daily dosing results in at least a 10% higher cure rate than a single dose is less than 0 001. Likewise, the risk of not detecting that a single dose results in an increased ototoxicity rate of at least 10% compared with multiple daily doses is less than 0-11, but the risk of not detecting that a single dose results in an increased nephrotoxicity rate of at least 10% compared with multiple daily doses is less than 0.28. Obviously, like Prins and co-workers, we recorded no difference in efficacy and ototoxicity between the two regimens, but by contrast with their findings our meta-analysis did not show any difference in nephrotoxicity. These results for nephrotoxicity are based on a total of 1356 evaluated patients-by contrast with the 85 patients in the study of Prins. The single-dose treatment may be ’1referred because of its convenience, but certainly not because of
Department of Medicine F, Hospital, Copenhagen, Denmark, Department of Medicine F and Y, Gentofte Hospital, and Department of Medicine P, Herlev
Bispebjerg Hospital, Copenhagen
A. M. GALLØE L. B. MADSEN N. GRAUDAL J. P. KAMPMANN
Rifampicin-resistant meningococci causing invasive disease and failure of
chemoprophylaxis SIR,-Rifampicin is recommended for the prevention of secondary cases among contacts of patients with invasive meningococcal disease. Despite the fact that rifampicin has been associated with the emergence of resistance in strains persisting in the throats of carriers,1-3 there are few reports of meningococcal disease due to rifampicin-resistant organisms after prophylaxis.4-6 We describe two small clusters of invasive meningococcal infection due to rifampicin-resistant meningococci, in which failure of chemoprophylaxis resulted in several secondary cases. In the first outbreak, a 6-year-old boy from a town in southern Israel (population about 15 000) was admitted on Jan 31,1993, with meningococcal meningitis. Within 72 h of onset, and before sensitivity results were known, rifampicin had been administered to all his family and other close contacts, including other children at the day-care centre and children attending a first-grade class there. Cultures of the patient’s cerebrospinal fluid (CSF) and blood yielded a serogroup C meningococcus, susceptible to penicillin (minimum inhibitory concentration [MIC] 0-001 mg/L) but resistant to rifampicin (MIC 256 mg/L). On Feb 14, a 7-year-old boy from the neighbouring class developed a clinical picture of meningococcaemia. He had received rifampicin after the initial case. CSF was normal, but blood cultures yielded a rifampicin-resistant (MIC 256 mg/L) group C meningococcus. As a result, chemoprophylaxis was repeated with intramuscular ceftriaxone for children (a single dose of 125 mg) and ciprofloxacin 500 mg in a single dose for adults. Both children recovered with appropriate antibiotic and supportive therapy. In the second outbreak, a 19-year-old man was admitted in February in central Israel with meningococcal meningitis. Close contacts were given rifampicin 600 mg orally twice a day for 2 days. CSF and blood cultures yielded a serogroup C meningococcus susceptible to penicillin (MIC 0 06 mg/L) and rifampicin (MIC 0-06 mg/L). 10 days later, a room-mate, who had taken rifampicin under supervision, was also admitted with meningitis. Again a group C meningococcus was grown from CSF and blood, this time fully resistant to rifampicin (MIC 256 mg/L), although sensitive to penicillin. Another round of chemoprophylaxis started with ceftriaxone 250 mg intramuscularly in a single dose. About 2 weeks later, the father of a third room-mate developed meningitis. The patient had had no contact with the first cases, but had spent some time with his son who had received attention for an undiagnosed febrile illness after receiving rifampicin in association with the first case. Again, a rifampicin-resistant (MIC 256 mg/L) group C strain was isolated. All the patients recovered. This report emphasises that rifampicin-resistant meningococci can cause systemic disease, and that rifampicin chemoprophylaxis may fail to prevent secondary cases. High-level resistance to rifampicin has not previously been observed in Israel and poses an important public health question. Israel is a small land with a small population (about 5 000 000), where the total number of cases of meningococcal disease reported per year rarely exceeds 90. These figures lend
THE LANCET
creatinine clearance, immunoreactive endothelin concentrations in plasma, blood pressure, and heart rate (measured automatically) in 30 patients with stones in the kidney, and in 19 patients with ureteric
improved efficacy or decreased toxicity. It is important to emphasise that most patients were evaluated unblinded (fourteen of sixteen studies were open and two were double-blind) and treated
stones.
with concomitant antibiotics. Crucial to the choice between the two regimens is whether one is prepared to run a risk of 28% of not detecting an increase in nephrotoxicity of 10% if the single-dose regimen is chosen. Although comparison of Prins and colleagues’ results with our meta-analysis shows that the results on efficacy and ototoxicity are much the same, we disagree about the possible beneficial effect on nephrotoxicity of the single-dose treatment.
One day after ESWL, 24 h urinary albumin excretion was increased by 125 (6) mg (p < 0-01 vs before ESWL) in patients with renal sones, and by 72 (3) mg in patients with ureteric stones (p < 0-05 vs before ESWL, p < 0-01 vs patients with renal stones). Although pre-existing impairment of kidney function improved in most patients between two and five weeks after ESWL, creatinine clearance measured on the day after ESWL showed an increase in patients with reduced renal function (creatinine clearance < 80 mL/min) by 12% in those with renal stones, but only by 3% in patients with ureteric stones (p <: 005). Immediately after ESWL, patients with renal stones had higher plasma concentrations of immunoreactive endothelin than those with ureteric stones (4-1 [0.2] vs 3-7 [0’4] pg/mL, p<0-05). This endothelium-derived vasoconstrictor hormone mediates, among other effects, a reduction in glomerular filtration rate. Thereafter, as well as before ESWL, endothelin concentrations were not different. Compared with before ESWL, mean arterial blood pressure in patients with renal stones increased by 8 [3] mm Hg between two and five weeks after ESWL (p < 001), and fell by 4 [2] mm Hg in those with ureteric
(p < 0-05). Although ESWL
stones
is non-invasive, these results suggest that moderate mechanical damage of kidney tissue may lead, at least in some patients, to a temporary impairment of renal function and an increase in mean arterial blood pressure, which is more pronounced if stones are close to, or in, the kidney. THOMAS HAAK Centre of Internal Medicine and Department of Urology,
University Hospital,
ECKART JUNGMANN DIETGER JONAS
6000 Frankfurt 70, Germany
KLAUS HENNING USADEL
S, Fair W, et al. Report of the United States cooperative study of extracorporeal shockwave lithotripsy. J Urol 1986; 135: 1127-33. 2. Karlsen SJ, Smevik B, Hovig T. Acute morphological changes in kidney function following extracorporeal shock wave lithotripsy for renal stones. Br J Urol 1991; 76: 1. Drach GW, Dretler
241-45. 3. Ackaert KSJW, Schroder FH. Effects of extracorporeal shock wave lithotripsy (ESWL) on renal tissue. Urol Res 1989; 17: 3-7. 4. Kaude JV, Williams CM, Millner MR, Scott KN, Finlayson B. Renal morphology and function immediately after extracorporeal shock-wave lithotripsy. Am J Radiol 1985; 145: 305-13.
Aminoglycosides: single or multiple daily dosing? SIR,-Dr Prins and colleagues conclude (Feb 6, p 335) that a once daily dosing regimen of gentamicin is at least as effective as and less nephrotoxic than more frequent dosing. To establish the best aminoglycoside regimen, we extracted data for efficacy, nephrotoxicity, and ototoxicity from sixteeen randomised trials of more than 1000 patients and showed that the cure rate of the single-dose regimen was 82-2% compared with 81-6% for the multiple-dose regimen; the ototoxicity rate was 3-0% compared with 4-1%, and the rate of nephrotoxicity was 8-6% in each group.
Although these differences are small and not significant, the results do not exclude the possibility of missing a real difference in the meta-analysis (type II error). For example, the risk of not detecting that multiple daily dosing results in at least a 10% higher cure rate than a single dose is less than 0 001. Likewise, the risk of not detecting that a single dose results in an increased ototoxicity rate of at least 10% compared with multiple daily doses is less than 0-11, but the risk of not detecting that a single dose results in an increased nephrotoxicity rate of at least 10% compared with multiple daily doses is less than 0.28. Obviously, like Prins and co-workers, we recorded no difference in efficacy and ototoxicity between the two regimens, but by contrast with their findings our meta-analysis did not show any difference in nephrotoxicity. These results for nephrotoxicity are based on a total of 1356 evaluated patients-by contrast with the 85 patients in the study of Prins. The single-dose treatment may be ’1referred because of its convenience, but certainly not because of
Department of Medicine F, Hospital, Copenhagen, Denmark, Department of Medicine F and Y, Gentofte Hospital, and Department of Medicine P, Herlev
Bispebjerg Hospital, Copenhagen
A. M. GALLØE L. B. MADSEN N. GRAUDAL J. P. KAMPMANN
Rifampicin-resistant meningococci causing invasive disease and failure of
chemoprophylaxis SIR,-Rifampicin is recommended for the prevention of secondary cases among contacts of patients with invasive meningococcal disease. Despite the fact that rifampicin has been associated with the emergence of resistance in strains persisting in the throats of carriers,1-3 there are few reports of meningococcal disease due to rifampicin-resistant organisms after prophylaxis.4-6 We describe two small clusters of invasive meningococcal infection due to rifampicin-resistant meningococci, in which failure of chemoprophylaxis resulted in several secondary cases. In the first outbreak, a 6-year-old boy from a town in southern Israel (population about 15 000) was admitted on Jan 31,1993, with meningococcal meningitis. Within 72 h of onset, and before sensitivity results were known, rifampicin had been administered to all his family and other close contacts, including other children at the day-care centre and children attending a first-grade class there. Cultures of the patient’s cerebrospinal fluid (CSF) and blood yielded a serogroup C meningococcus, susceptible to penicillin (minimum inhibitory concentration [MIC] 0-001 mg/L) but resistant to rifampicin (MIC 256 mg/L). On Feb 14, a 7-year-old boy from the neighbouring class developed a clinical picture of meningococcaemia. He had received rifampicin after the initial case. CSF was normal, but blood cultures yielded a rifampicin-resistant (MIC 256 mg/L) group C meningococcus. As a result, chemoprophylaxis was repeated with intramuscular ceftriaxone for children (a single dose of 125 mg) and ciprofloxacin 500 mg in a single dose for adults. Both children recovered with appropriate antibiotic and supportive therapy. In the second outbreak, a 19-year-old man was admitted in February in central Israel with meningococcal meningitis. Close contacts were given rifampicin 600 mg orally twice a day for 2 days. CSF and blood cultures yielded a serogroup C meningococcus susceptible to penicillin (MIC 0 06 mg/L) and rifampicin (MIC 0-06 mg/L). 10 days later, a room-mate, who had taken rifampicin under supervision, was also admitted with meningitis. Again a group C meningococcus was grown from CSF and blood, this time fully resistant to rifampicin (MIC 256 mg/L), although sensitive to penicillin. Another round of chemoprophylaxis started with ceftriaxone 250 mg intramuscularly in a single dose. About 2 weeks later, the father of a third room-mate developed meningitis. The patient had had no contact with the first cases, but had spent some time with his son who had received attention for an undiagnosed febrile illness after receiving rifampicin in association with the first case. Again, a rifampicin-resistant (MIC 256 mg/L) group C strain was isolated. All the patients recovered. This report emphasises that rifampicin-resistant meningococci can cause systemic disease, and that rifampicin chemoprophylaxis may fail to prevent secondary cases. High-level resistance to rifampicin has not previously been observed in Israel and poses an important public health question. Israel is a small land with a small population (about 5 000 000), where the total number of cases of meningococcal disease reported per year rarely exceeds 90. These figures lend