Profilakse van urinere infeksie by vroue Cyclosporin A and organ ...

Suid-Afrikaanse Mediese Tydskrif
South African Medical Journal
27 JUNIE/JUNE 1981 DEELlVOLUME 59 NO. 27
Van die Redaksie/Editorial
Profilakse van urinere infeksie by vroue
Akute sistitis lei menige jong vrou na die dokter se
spreekkamer - in die VSA word besoeke daarvoor
bereken op vyf ma31 per jaar. 1 Profilakse is reeds jare lank
aanbeveel. Oat dit effektief is, is 31 menige kere bewys.2-6
Daaglikse trimetoprim-sulfametoksasool (TS), trimetoprim
aUeen en nitrofurantolen lewer a1mal goeie resultate
in die verband.
Twee faktore is van belang: eerstens, sulke profilakse
mag die ontstaan van weerstandbiedende crganismes
aanhelp; en tweedens, regverdig die koste-effektiwiteit
dit? Dit is gestel dat 6 maande se profilakse met TH tweederdes
van die koste vir die behandeling van een infeksie
beloop.7
Stamm er al. 8 in Washington, VSA, het die kostes
vergelyk van profilakse en plasebo by 117 pasiente wat
akute urinere infeksies van 'n ongekompliseerde aard
gehad het. Hulle het gevind dat die jaarlikse koste van
profliakse (S85) minder was as die van behandeling van
akute episodes ($392) wanneer daar 'n basislyn
infeksiesyfer van drie per pasient per jaar is. By vroue wat
onderhewig was aan drie infeksie-episodes per jaar en by
wie die koste per episode $42 oorskry het, was die
profliaksekoste effektief.
Die waarde van chemoprofliakse vir bakteriele infeksies
is benvisbaar. Dikwels is dit nie etlektief nie,
weerstandbiedende organismes ontsraan en die agens self
mag nadelige effekte he. Hierdie klassieke beginsels word
31mal geskend deur die voorstaanders van chemoprofliakse
vir urinere infeksies by vroue. 9
Die newe-effekte waarna daaropgelet moet word behels
o.m. chroniese interstisiele pneumonitis, akure pulmonere
hipersensitiwiteit, allergiese reaksies, lewerskade,
bloeddiskrasiee en neuropatie. Hierdie effekte is nie altyd
te wyre aan die sterkte van die dosis nie en ook nie aan die
tydperk waaroor dit toegedien is nie.
Effektiewe profilakse bestaan o.m. uit metenamienmandelaat
500 mg saam met askorbiensuur 500 mg, 4
keer per dag; nirrofurantolen 50 mg/d; TS 40 : 200 mg/d,
trimetroprim alleen of sulfametoksasool 500 mg/d. Dit is
selfs bew'ys dat een TS pil 3 keer per week effektief is.
Hoe lam moet daar dan met chemoprofilakse aangehou
word? Volgens Ronald er at. 9 moet hulle eers 6 maande
aanhou. Indien 'n akure episode binne 3 maande geskied,
word dit behandel en dan word profilaktiese behandeling
vir 2 jaar toegedien. Vosti 10 het 14 vroue suksesvol
behandel met chemoterapie na kOltus waar dit geblyk het
dat infeksie op kOltus gevolg het. Topiese antibakteriele
terapie is nog nie deeglik beproef nie. Enkeldosisbehandeling
vir akure infeksies van die onderste dele van
die urinere trakrus is bewys om net so effektief te wees as
7-10 dae se konvensionele behandeling.
Dit mag wel wees dat sommige pasiente persisterende
infeksie binne die ren31e parenchiem het wat net deur
chemoprofilakse onderdruk word, sonder dat dit uirgewis
word. Hierdie risiko moet nog ondersoek word soos vele
ander ook, waarvan nie die minste 'n geskikte regimen vir
pasiente met renale versaking is nie. Dit is ook nodig om te
weet of profI1akse die akute uretr31e sindroom sal
voorkom.
L National Center for Health Statistics (1975): Adv. Data, 12, 1.
2. Harding, G. K. M. ec al. (1974): New Engl. J. M.ed., 291, 597.
3. Stamey, T. A. ec al. (197/ : Ibid., 296, 780.
4. Fairley, K. F. ec al. (1967): Lancet, 2, 427.
5. Holland, N. H. ec al. (1963): Amer. J. Dis. Child., lOS, 560.
6. Stamm, W. E. ec al. (1980): Ann. intern. Med., 92, 770.
7. Kraft, J. K. ec al. (1977): Medicine (Baltimore), 56,55.
8. Stamm, \X'. E. ec al. (1981): Ann. intern. Med., 94, 251.
9. Ronald, A. R. ec al. (198!): Ibid., 94,268.
10. Vosti, K. L. (1975): J. Amer. med. Ass., 231, 934.
Cyclosporin A and organ transplantation
In 1976 Dreyfuss er al. 1 isolated the endecapeptide
cyclosporin A (CyA) from the fungi Cylindrocarpon
lucidum and Tn·choderma polysporum, and soon afterwards
this was shown to have immunosuppressive propenies 2
and to exercise a preferential action on human T
lymphocytes in suppressing allogeneic response. 3 This
powerful immunosuppressive action was confirmed in
vivo by C31ne er al. 4 in patients receiving renal transplants
from cadaver donors. Itnow looks as ifthe use ofCyA may
963
prove a major advance in transplant surgery despite the
drawback of its nephrotoxicity.
In 1979 Calne er al. 5 used CyA as the sole
immunosuppressant in 34 recipients of organ transplants
(kidney 32, liver, pancreas) bur encountered 11 cases of
nephrotoxicity with oliguria or anuria. In the mistaken
belief that this response represented a rejection reaction
they added corricosteroids and a cyclophosphamide
analogue bur the resulting excessive immunosuppression

J with
964 SA MEDICAL JOURNJl:L 27 JUNE 1981
led to a high incidence of bacterial, viral and fungal
infection and to the development of 3 lymphomas. When
the dose of CyA was reduced severe graft rejection
developed, bur this was rapidly controlled by substituting
azathioprine and prednisolone for CyA. They also
believed that the use of CyA was made safer by forced
diuresis.
Klintmalm er al. 6 of Colorado have recently reported
the use of CyA in liver and kidney transplantation bur
believe that early kidney failure in these cases is more
likely to be due to graft rejection than to drug toxicity.
However, they noted nephrotoxicity after 13 - 22 days in 6
out of 12 patients with orthotopic liver transplants treated
with CyA in doses of 11 - 20 mg/kg daily. In 4 renal
transplant cases there was also evidence ofnephrotoxicity,
sharp rises in serum creatinine and blood urea
nitrogen on doses as low as 5,2 mg/kg daily. However,
they found that this toxicity was easy to combat by
lowering the dose of CyA and/or a switch to azathioprine
as immunosuppressant.
Since there is clearly a need to establish a dose range
that will produce adequate immunosuppression withour
nephrotoxicity, Keown er al. i of the University of
Western Ontario have monitored serum levels ofCyA and
measured these against the immune response in kidney
recipients to donor antigens after a transplant. The drug
was given intramuscularly during the first 48 hours and
then orally as a dose of 17,5 mg/kg/d.
The graft functioned at once in 5 our of 6 cases and the
authors suggest that the drug is best given orally twice a
day for adequate immunosuppression. They think that it
has a biological half-life of4 - 6 hours and in the dose given
maintains a continuous serum level in excess of0,1 pg/ml
for 12 hours. They are, however, unhappy about a slowly
progressive deterioration in renal function in 4 patients,
beginning after abour 3 months.
Calne er al. 8 have J;ecently reviewed their results with
the use of CyA in renal, hepatic and pancreatic grafts and
seem very satisfied with its use so far. They describe
results with three groups of patients: (z) 39 patients with
kidney grafts given CyA as the initial sole
immunosuppressive agent; (iz) 14 patients with liver or
kidney grafts converted to CyA treatment; (iiz) 9 patients
with segmental pancreatic allografts for insulindependent
diabetes.
Their results with CyA in patients given cadaveric
renal allografts were very much better than had been
obtained before. The predicted graft survival at 1 year
was 86%, bur the group included 5 patients in whom CyA
did not control rejection and who were changed to
azathioprine and corticosteroids with satisfactory results.
They disagree with Starzl er al.,9 who suggest that CyA
should be combined with corticosteroids, because of the
British experience of a high incidence of infections and
lymphoma with this combination.
With liver allografts they start CyA only when ·the
patient's condition is stable, and find that hepatic and
renal function can be satisfactorily maintained with this
drug alone, but the follow-up term is short. CyA has also
controlled rejection in some cases of pancreas
transplantation without the need for corticosteroids; their
problem is more the prevention of exocrine secretion by
blocking of the pancreatic ducts.
The ease with which patients may be changed to and
from CyA provides a valuable alternative immunosuppressive
tool, and a randomized multicentre trial is
now being planned to compare CyA with the conventional
azathioprine-eorticosteroid regimen in recipients of
cadaver renal allografts.
1. Dreyfuss, M., Haerri, E., Hoffman, H. ec al. (1976): Eur. J. appl. Microbial., 3,
125.
2. Bore!, J. F. (1976): Immunol.ogy, 31, 631.
3. Gordon, M. Y. and Singer, J. W. (1979): Nature, 279, 433.
4. Calne, R. Y., White, D. J. G., Thiru, S. et al. (1978): Lancer, 2,1323.
5. Calne, R. Y., Rolles, K., Whire, D. J. G. et al. (1979): Ibid., 2, 1033.
6. Klinrmalm, G. B. G., Iwarsuki, S. and 5rarzl, T. E. (1981): Ibid. L 1,470.
7. Keown, P. A., Sriller, C. R., Ulan, R. A. er al. (1981): Ibid., 1,686.
8. Calne, R. Y., Whire, D. J. G., Evans, D. B. (1981): Bri!. med. J., 282, 934.
9. Srarzl, T. E., Weil, R., Iwarsuki, S; et al. (1981): Surg. Gynec. Obsre!., 151,17.