CITATION: Theron, F. P. & De Kock, M. A. 1977. Clinical experience with amikacin, a new aminoglycoside antibiotic. South African Medical Journal, 51(21):746-8.The original publication is available at http://www.samj.org.za[No abstract available]Publisher’s versio

De Kock, M. A.

Theron, F. P.

Stellenbosch University SUNScholar Repository

746 SA MEDIESE TYDSKRIFTABLE I. PELVIC RADIOGRAPHS OF 727 WHITES RESULTS21 Mei 1977Male FemaleAge(yrs)0-2021 - 3031 - 4041 - 5051 - 6061+TotalWithoutphleboliths304839272331198Withphleboliths11430303136142Withoutphleboliths456237192021204Withphleboliths3830354859183Tables I and 1I indicate the frequency of phlebolithsaccording to race, age and sex. Blacks have far fewerphleboliths than Whites and the results are meaningful atthe I % level of significance.Fig. 1 shows the differing rates of increase with agein the proportion of people with phleboliths. It is possiblethat the dip in the graph of the Black group is due to anincreasing incidence in younger, westernized people.REFERENCESTABLE 11. PELVIC RADIOGRAPHS OF 823 BLACKSMale FemaleAge Without With Without With(yrs) phleboliths phleboliths phleboliths phleboliths0-20 54 0 54 021 - 30 70 4 85 731 - 40 54 6 81 1641 - 50 87 9 96 2451 - 60 38 11 41 1561+ 18 8 34 11Total 321 38 391 73I. Walker, A. R. P. (197 I): S. Afr. med. J., 45, 377.2. Idem (1973): Postgrad. med. 1., 49, 243.3. Burkitt, D. P. (1975): Canad. J. Surg., 18, 483.4. Idem (1969): Lancet, 2, 1229.5. Idem (1970): Ibid., 2, 1237.6. Idem (1973): Brit. med. J., 1, 274.7. Idem (1976): S. Afr. med. J., 50, 2136.8. Painter. N. S. (1974): Diverticular Disease of {he CO/Oil (Present Stateof Kno\'1ledge No. 1). London: Norgine.9. Cleave, T. L. and Campbell, G. D. (1969): Diabetes, CorollaryThrombosis and rhe Saccharine Disease. Bristol: John Wright & Sons.10. Prior, I. A. M., Rose, B. S. and Davidson, F. (1964): Brit. med. J.,1, 1065.11. Sorokin, M. (1975): S. Afr. med. J., 49, 148 I.12. Daynes, W. G. (1973): Ibid., 47, 318.13. Van Niekerk, J. M. (1977): Personal communication.14. Clark, G. O. (1909): Ann. Surg., 50, 913.15. Culligan, J. M. (1926): J. Uro!. (Baltimore), 15, 175.16. Franz, R. C. (1961): Lancet, I, 195.Clinical Experience with Amikacin, aNew .i\minoglycosideAntibioticF. P. THERON,SUMMARYAmikacin, a new semisynthetic aminoglycoside antibiotic,was administered parenterally to 20 patients sufferingfrom severe Gram-negative bacterial infections. The anti-biotic was found to be highly effective in controlling in-fection. It was well tolerated and no signs of nephro- orDeparhncnt of Medicine, University of Stellenbosch andTygerbcrg Hospital, ParOln'allei, CPF. P. THERON. :\I.B. CH.B .. M. MED..\1. A. DE KOCI\:. :\f.8. CH.B .. :\1. :\1£D.. F.C.P. (S.A.), :\1.D..F.B.C.P.) F.A.C.C.P.Date received: 11 January 1977.Reprint requests to: Professor M. A. de Kock, Department of Medicine.University of Srellenbosch Medical School, PO Box 63. Parowvallei, 7503RSA.M. A. DE KOCKototoxicity were observed. The few side-effects whichwere seen appeared to be dose-related. The recommended12-hourly dosage regimen has also proved useful inmedium- to long-term management of refractory pulmo-nary infections.S. Afr. med. J., 51, 746 (1977).Amikacin (BB - K8) is a semisynthetic aminoglycoside anti-biotic derived from kanamycin. It has pharmacologicalproperties similar to those of the parent substance, kana·mycin. Amikacin has an extremely broad spectrum ofantibacterial activity, and is claimed to be more resistantto aminoglycoside-inactivating enzymes than any amino-glycoside in current clinical use.' In common with relatedaminoglycosides, amikacin might be expected to possess11 May 1977 SA MEDICAL JOCRNAL 410xic properties. particularly in respect of the patient withimpaired renal function. Gentamicin, for example. habeen shown to produce acute nephrotoxicity ami ototoxi-city, and to possess neuromuscular blocking potentiaL""Animal experimentation has uggested that the tendencyto cause toxicity noted in the specific drug under trialwas probably dose-related, occurring consistently in thedosage range of 30 mgjkg/d.'·' Such levels exceed by asubstantial margin the recommended daily dose (15 mg kg)of amikacin for clinical use.The purpose of this study was to evaluate the preclinicaltherapeutic claims made for the efficacy of amikacin incombating Pseudomonas organisms and other Gram-nega-tiv~ bacteria frequently implicated in drug-resistant micro-bial infections. particularly of the lungs.PATIENTS AND METHODSPatient SelectionAll the subjects participating in the trial had givenwritten informed consent to the administration of amikacinin the treatment of their disease. It was explained to themthat the wider effects of the drug were unknown, althoughthe limited clinical trials conducted elsewhere to date hadyielded very few untoward effects. and that the latter hadbeen similar to those encountered with other drugs in theaminoglycoside group currently in general use.There were 20 patients with mixed Gram-negative in-fections which had. in 25.... of cases. previously beentreated unsuccessfully with other antibiotic drugs. Theseriousness of the patients' illnesses did not permit theincorporation of double-blind techniques employing alter-native aminoglycoside drugs in the design of the trial,and no control could be exercised other than thorough andobjective clinical and laboratory ob ervation.The age of the patients varied from l-l to 70 year(average 47.5 years) and there were 14 male and 6 femaleubjects. Fourteen of these patient could be classified asseriou Iy ill with life-threatening infections. while the re-mainder had moderately severe infections. The primarydiagnoses are detailed in Table I. and these included avariety of bronchial. parenchymal and pleural pulmonaryinfe tion and a single case of septicaemia proved on bloodculture.MethodsAll patients were individually evaluated by the authorsbefore undergoing a predetermined set of investigationsprior to the institution of amikacin therapy. This docu-mentation included the following:(a) the measurement of height and body mass:(b) the maintenance of fluid balance charts, with regularmicroscopical and biochemical urinalysis:(c) complete blood cell counts;(d) liver function tests;(e) the evaluation of auditory and vestibular function- after consulting our Ear. Nose and Throat De-partment. we considered the following tests ade-quate for our purposes: audiogr-aphy and enquiryafter conversational deafness, vertigo and tinnitusand examination for nystagmus;(f) serum creatinine and blood urea determinations;(g) records of arterial blood pressure, pulse rate andoral temperature. charted 6-hourly;(h) daily bacteriological culture of collected sputum.TABLE I. SUMMARY OF PATIENT DATADuration of Amikacin Duration ofCase illness dosage treatmento. Age Primary diagnosis Causative organism (days) Prior therapy (mg/kg/d) (days) Result64 Bronchopneumonia Klebsiella pneumoniae 10 Ampicillin 12,0 17 FairPenicillin, ampi-2 63 Bronchopneumonia Gram-negative 5 cillin 12,0 13 Excellent3 25 Septicaemia Pseudomonas aeruginosa 2 Nil 19,5 8 ExcellentStreptomycin, INH,4 36 Empyema Proteus mirabilis 30 ethambutol 17,8 21 Excellent5 45 Lobar pneumonia Klebsiella pneumoniae 14 Nil 15,1 9 Excellent6 45 Lung abscess Gram-negative 7 Nil 19,6 44 Good7 55 Bronchopneumonia Klebsiella pneumoniae 10 Nil 14,2 5 Excellent8 65 Bronchopneumonia Enterobacter 14 Nil 27,0 10 Poor9 51 Lobar pneumonia Klebsiella pneumoniae 2 Nil 16,6 22 Good10 18 Bronchopneumonia Klebsiella pneumoniae 7 Nil 24,3 8 Excellent11 70 Bronchopneumonia Unknown 7 Nil 15,3 8 Excellent12 14 Bronch'ectasis Pseudomonas aeruginosa 14 Nil 27,3 12 Good13 60 Lobar pneumonia Klebsiella pneumoniae 2 Nil 19,2 10 Good14 61 Bronchiectasis Pseudomonas 4 Amoxycillin 20,8 7 Excellent15 53 Bronchopneumonia Klebsiella pneumoniae 3 Ampicillin 19,2 10 Excellent16 45 Lobar pneumonia Klebsiella pneumoniae 14 Nil 17,5 10 Excellent17 48 Bronchiectas is Klebsiella pneumoniae 21 Nil 15,0 7 Excellent18 25 Bronchopneumonia Klebsiella pneumoniae 10 Nil 22,6 10 Excellent19 67 Lung abscess Klebsiella pneumoniae 14 Nil 15,1 19 Excellent20 40 Lobar pneumonia Klebsiella pneumoniae 5 Nil 15,3 9 Excellent12=748 SA EDIESE TYDSKRIF 21 Mei 1977These investigations were repeated at regular intervalsor continued throughout the period of drug trial therapy,and were maintained for some days after the cessation oftreatment, subject to the emergence of side-effects ascribedto the drug. The results of therapy were assessed in termsof the clinical response, being adjudged excellent, good,fair or poor, according to such criteria as improvement intoxic-febrile state. diminished cardiac and respiratory rates,favourable leucocyte and sedimentation rate response, and.most important, the persistent absence of the offendingpathogen from the patient's sputum, signifying eradicationof the Gram-negative infection.RESULTSA summary of the patient data is provided in Table 1.The findings in 6 patients deserve further discussion inview of the opportunistic nature of the infection in acompromised host situation, presumably unrelated super-vening clinical events, the emergence of side-effects of thedrug, or failure of antibiotic therapy to prevent irreparableloss of function.The clinical and bacteriological response to amikacin inpatient 7 was excellent. He made rapid progress towardscomplete recovery, only to succumb unexpectedly to acuteanterolateral myocardial infarction on the fifth day oftherapy.Patient 12, a 14-year-old girl with mucoviscidosis andproven secondary amyloidosis and a long history of re-current pulmonary infection in relation to bronchiectasis,developed acute bronchitis with marked central cyanosis.Pseudomonas aeruginosa was cultured from the sputumand amikacin was commenced as primary antibiotic therapy.In view of the severity of the infection, and the criticalgeneral condition of the patient, she received a very highdosage, 27,3 mg/kg/d. The clinical response to the drugwas good and the pathogen was eradicated from the sputumwithin 14 days, but the blood platelet count had decreasedfrom the control value of 340000/,Lt1 to 62000/,Lt1 at thisstage and the drug was discontinued. The thrombocytecount gradually returned to normal levels within 2 weeksand the patient's further clinical progress was satisfactory.The only other untoward effect of the drug noted inthis series occurred in patient 6. He was a 45-year-oldman who received amikacin as initial antibiotic treatmentfor a lung abscess. The dosage of the drug was high (19,6mg/kg/d), and was of necessity prolonged in view of thenature of the pathology and the difficulty experienced ineradicating a variety of Gram-negative pathogens. On the44th day of therapy the patient developed a non-bullousform of erythema multi forme, which regressed promptlyafter withdrawal of the drug and the administration ofa short course of steroids. The overall clinical responsewas good and the patient's progress to recovery continuedon alternative antibiotic therapy.Patient I, a 64-year-old man in a pre-terminal stateassociated with advanced lymphocytic lymphoma, wastreated with amikacin when a bronchopneumonic infectioncould not be controlled with ampicillin. The clinical im-provement observed with trial drug therapy was initiallyencouraging, but Klebsiella pneumoniae was persistentlycultured from the sputum, necessitating a change to alter-native aminoglycoside therapy with gentamicin and, sub-sequently, tobramycin. The bacteriological response to thelatter drugs was, however, indifferent and at the time of thepatient's death 6 months later, sputum culture was stillpositive for K lebsie/la.The clinical response to the drug achieved in patient 8was coded as poor. This elderly woman had severe chronicobstructive airways disease complicated by bronchopneu-monia. Enterobacter was implicated and amikacin therapywas commenced. The patient's temperature chart showeda swinging pyrexia which subsided after several days,and sputum culture became negative. Antibiotic and othersupportive therapy failed to halt the progressive parenchy-mal destruction, however, and the worsening respiratoryfailure resulted in death from irreversible hypoxaemia.Patient 4 is worthy of comment. This patient was treatedfor empyema but was also receiving antituberculosis thera-py. including streptomycin. We were reluctant to use twoaminoglycosides simultaneously. but this was thought justi-fied in view of the patient's life-threatening Gram-negativeinfection amikacin in a dosage of 17,8 mg/ kg/ d wasgiven.CO CLUSIO SOur experience. although limited, suggests that amikacin isa valuable adjunct to current antibiotic therapy, particu-larly in respect of Gram-negative pathogenic organismswhich are likely to prove resistant to all but aminoglycosidetreatment.In view of the severity and refractoriness of the in-fection in a number of cases, the dosage employed fre-quently exceeded the manufacturer's recommendation of15 mg/ kg/ d. Patients 8, 10, 12 and 18 in particular werethought to deserve high dosages by virtue of their life-threatening condition. However, the daily dose administeredfell short of the 30 mg/kg/d level which has been quotedin the literature as consistently producing toxicity in ani-mals treated with gentamicin and other aminoglycosidedrugs.'"Side-effects ascribable to the use of the drug in thepresent study were limited to two instances where excep-tionally high dosages were used and were 'nonspecific'in nature, suggestive of a hypersensitivity response. Bothwere reversible, and unrelated to the nephrotoxic, ototoxicand neuromuscular blocking effects previously documentedin respect of drugs in this group. It is concluded that ami-kacin is an effective antibiotic which may be employed withconfidence in patients with life-threatening aerobic Gram-negative infections, provided that there is reasonable renalfunction and that the dosage does not exceed 20 mg/kg/d.We should like to thank the BM Group (Pty) Ltd for thesupply of amikacin.REFERE, CES1. Price. K. E .. Cbisholm, D. R. and Misiek, M. (1972): J. AntibioL(Tokyo), 25, 709.2. Arcieri, D. M. et at. (1975): Med. J. Aust., I, June suppl.3. Hewitt, W. L. (1974): Postgrad. med. J., 50, November suppl., p. 55.4. Brummet, R. E., Himes, D. and Saine, B. (1972): Arch. Otolaryng.,96, 505.5. Welles, J. S., Gib.on, W. R., Emmerson, J. L. et al. (1973): Toxieol.appl. Pharmacol., 25, 398.

Clinical experience with amikacin, a new aminoglycoside antibiotic

http://scholar.sun.ac.za/bitstream/10019.1/7711/1/theron_clinical_1977.pdf

Clinical experience with amikacin, a new aminoglycoside antibiotic

Abstract

Similar works

Full text

Available Versions

Stellenbosch University SUNScholar Repository