Gentamicin: use of a programmable calculator to determinedosages from pharmacokinetic data for individual patients

LouIS DE REPENTIGNY, MD; Louis DUMONT, B SC; JACQUES LE LORIER, MD; RICHARD MORISSET, MD;PIERRE LAROCHIELLE, MD; YVES COURCHESNE, B SC PHARM

Gentamicin, an antibiotic frequently used in the treatment ofgram-negative infections, has a narrow therapeutic index, sothe correct prediction of its serum concentrations is im-portant. Recent studies have emphasized the dubious ac-curacy of commonly used formulas, and computer programsthat provide pharmacokinetic data for individual patientsfrom multiple blood samples have helped to adjust dosagesbut are expensive.

This study tested the applicability of a method using onlytwo blood samples and a programmable calculator to es-timate pharmacokinetic parameters for individual patientsand adjust dosages to aim at peak and trough serum levelsof 6 and I p.g/ml respectively. In the 48 patients with normalrenal function this method produced peak serum concen-trations of gentamicin within I Vg/ml of the desired level in22 (46%) and therapeutic peak concentrations (between 4and 10 ,ug/ml) in all the patients. In 10 patients with renalfailure it produced peak serum concentrations within 1 mg/mlof the desired value in 4 and therapeutic serum concentra-tions in 7. Two patients had peak concentrations below4 Vg/ml and one had a peak concentration above 10 ug/ml.Two of the three patients whose serum levels were outsidethe therapeutic range had unstable renal insufficiency. Thus,patients with renal insufficiency need continued monitoringof the serum level of gentamicin, particularly when theirrenal function is changing.

La gentamicine, un antibiotique souvent utilise dans le traite-ment des infections a bacteries gram-negatif, possede unindex therapeutique etroit, d'ou l'importance de pouvoirpredire correctement ses concentrations seriques. Desetudes recentes ont mis en evidence la precision douteusedes formules d'usage courant, et les programmes d'ordina-teur capables de donner pour chaque patient les donneespharmacocinetiques a partir de multiples prelevements san-guins ont permis d'ajuster les doses mais ils sont couteux.

La presente etude a teste la possibilite d'application d'unemethode qui, avec seulement deux echantillons de sang etune calculatrice programmable, peut evaluer pour chaquepatient les parametres pharmacocinetiques et ajuster lesdoses pour atteindre une concentration serique maximum de6 pg/ml et une concentration serique minimum de I Lg/ml.Cette methode a permis d'obtenir des concentrations seri-ques maximums de gentamicine a I Vg/ml pres des niveauxdesires chez 22 (46%) des 48 patients ayant une fonctionrenale normale, et tous ont eu une concentration seriquemaximum therapeutique (comprise entre 4 et 10 u,g/ml).Parmi les 10 patients ayant une insuffisance renale 4 ont euun taux serique maximum a I ,ug/ml pres de la concentra-tion desiree et 7 ont obtenu des concentrations seriques the-

From the department of medicine, H6tel-Dieu de Montrealand the department of pharmacology, faculty of medicine,University of Montreal

Reprint requests to: Dr Jacques Le Lorier, Hotel-Dieude Montreal, 3840, rue St-Urbain, MontreaI, PQ H2W 1T8

rapeutiques. Deux patients ont presente des concentrationsmaximums inferieures A 4 sLg/ml et un avait un taux maxi-mum depassant 10 t±g/ml. Deux des trois patients dont lestaux seriques se situaient a l'exterieur de la marge thera-peutique souffraient d'insuffisance renale instable. Enconsequence, les patients souffrant d'insuffisance renalenecessitent une surveillance continue des taux seriques degentamicine, particulierement quand leur fonction renaleest changeante.

Gentamicin, a frequently used aminoglycoside anti-biotic, is effective in the treatment of infections causedby susceptible gram-negative bacteria.1 The effectiveserum concentrations lie in a narrow range, between4 and 10 ,ug/ml.2` The two main types of side effects,ototoxic and nephrotoxic, are usually associated withpeak levels above 12 ,ug/ml"57 or trough levels greaterthan 2 ,4g/ml;5 however, toxic effects have also beenobserved during periods of therapeutic blood levels.It has also been stressed in the literature that serumlevels of gentamicin vary widely from patient to patienteven when the dosages are adjusted to take into ac-count the patient's lean body weight and renal func-tion.4'8-0 This variability is particularly important inthe presence of renal insufficiency, for gentamicin isnot metabolized and is almost totally eliminated by thekidneys.To overcome the problem caused by the wide vari-

ability in serum levels between patients two approacheshave been used. The first has been to improve exist-ing nomograms by calculating dosages on the basis ofthe patient's lean body weight rather than total bodyweight, a reasonable strategy if one considers that gen-tamicin is not liposoluble. It has recently been shownthat this increases the percentage of patients that willhave serum levels within the therapeutic range.11 Thesecond approach consists of estimating pharmacokin-etic parameters in each patient by means of the serumlevels measured after the initial dose of gentamicinhas been administered in a conventional manner. Theseparameters are then used to determine the dosageneeded to achieve a predetermined serum concentra-tion. 12,13

Although the approach involving the lean body weightis a noticeable improvement over previous methods itstill occasionally results in serum levels above or belowthe therapeutic range.'4 The pharmacokinetic approachis very successful in achieving the desired serum levelsbut is burdensome, in that it requires multiple bloodsamples and expensive computer hardware.We assessed the clinical applicability of a simplified

pharmacokinetic method requiring only two bloodsamples and a programmable calculator.

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MethodsPatients

Fifty-eight patients receiving gentamicin intravenous-ly for proved or suspected gram-negative infectionswere studied in the medical, surgical and gynecologicdepartments of H6tel-Dieu de Montreal, a teachinghospital affiliated with the University of Montreal. Ofthe 58 patients 48 had normal renal function and 10had various degrees of renal insufficiency (Table I).The patients were divided into three groups. Group

1 consisted of 24 patients with normal renal functionin whom the initial dosage of gentamicin was 1 mg/kgof body weight three times a day. The serum level ofgentamicin was determined in two blood samples andthe individual pharmacokinetic parameters were cal-culated. The dosages were then adjusted to aim forpeak and trough concentrations of 6 and 1 ,ug/mlrespectively. Blood samples were again drawn to seehow close the obtained levels were to those desired.

Group 2 was composed of another 24 patients withnormal renal function whose initial gentamicin dosageswere determined from the dosing chart of Hull andSarubbi,'1 which specifies a loading dose of 1.75mg/kg. In patients whose total body weight was lessthan the calculated lean body weight the smaller valuewas used to determine the dosage. Again, individualpharmacokinetic parameters were calculated and dos-ages adjusted to aim for peak and trough concentra-tions of 6 and 1 ,g/ml respectively. Blood sampleswere also drawn again in this group to see how closethe obtained levels were to those desired.Group 3, the 10 patients with renal insufficiency,

was studied in the same manner as group 2.

Measurement of serum levels of gentamicin

Gentamicin was infused half an hour at fixed inter-vals in all patients. After three infusions blood sampleswere drawn 5 minutes after a given infusion (usuallythe fourth) to determine the peak serum level of theantibiotic and immediately before the next infusionto determine the trough level. These levels were de-termined in duplicate samples on the same day by aradioimmunoassay (Monitor Science Corporation,Long Beach, California) with a sensitivity of 0.1 ,g/mland a coefficient of variation of 5% at a mean valueof 6.5 ,ug/ml.

Pharnmacokinetic calculations

Pharmacokinetic parameters were calculated foreach patient from the peak and trough serum genta-micin concentrations, assuming a first-order elimina-tion rate constant in a one-compartment, open model.All the calculations were done on a pocket-sized pro-grammable calculator (model HP-67, Hewlett-PackardCompany, Avondale, Pennsylvania).*

The serum concentration-time data were first fittedto a single exponential term by nonlinear regressionanalysis. This fit provided an estimate of the elimina-

tion rate constant (k,1). The volume of distribution(Vd) of gentamicin was then calculated as follows:

Vd ko(l-e kdt ),kei(Cm.-Coe kdt')

where k,, is the rate of infusion of the test dose, t' isthe infusion period (in this case half an hour) and Cois the serum concentration of gentamicin just beforethe next dose is given (the trough level). The totalbody clearance (TBC) of gentamicin was calculatedthus:

TBC = keiVd

The desired maximum (peak) and minimum (trough)serum concentrations of gentamicin were arbitrarilyselected for all patients as 6 and I ,ug/ml respectively.The dosing interval (T) was then calculated as follows:

l-t't= 1 In (Cm"'elC.inax)

The interval was rounded to the nearest even value (inhours), then the infusion rate (ko) required to producethe desired maximum serum concentration was ob-tained thus:

Ko= k,I.Vd C,,.x I-eekdT

Results

The mean serum concentrations of gentamicin be-fore and after individualization of therapy are givenin Table II.Of the 24 patients in group 1, 5 had peak serum

concentrations of gentamicin below the minimum ther-apeutic level of 4 ug/ml when the dosage was based ontotal body weight alone. After individualization oftherapy all 24 patients had therapeutic peak concentra-tions, and in 46% the peak was within 1 ,ug/ml of thatdesired (6 ,ug/ml). In this group the mean change indose was 23 mg (minimum 0, maximum 140 mg) andthe mean change in dosing interval 2.9 hours (minimum0, maximum 12 hours).None of the 24 patients in group 2 had peak serum

-concentrations of gentamicin below the minimum ther-

Table I-Characteristics of the 58 patients

Group;* mean 4 standard deviation (SD)Group 1 Group 2 Group 3

Characteristic (n= 24) (n= 24) (n= 10)Age (yr) 47.5 19.6 50.8 14.8 63.3 ± 15.4Total body weight (kg) 56.0 + 13.2 65.9 + 16.3 73.9 ± 17.1Desirable weight (kg) 52.1 s 10.0 58.4 s 11.5 61.3 ± 11.7Estimated creatinineclearance (ml/min) 85.8 ± 35.4 88.5 27.5 31.4 i 15.7

*See text for definitions.

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*The program and instructions for its use are available uponrequest from Dr. Le Lorier.

apeutic level when the dosage was based on lean bodyweight alone. One patient had a very high peak level(16.0 ,ug/ml), but after modification of her dosage to30 mg every 6 hours the peak serum concentration fellto 4.2 ug/ml, which is within the therapeutic range.

As in group 1 all the patients had therapeutic peakserum concentrations of gentamicin after individualiza-tion of therapy, and in 46% the peak was within 1,ug/ml of that desired. In this group the mean changein dose was 23 mg (minimum 0, maximum 60 mg)and the mean change in dosing interval 2.3 hours(minimum 0, maximum 10 hours).

Of the 10 patients in group 3, only 4 had peak se-rum concentrations of gentamicin within the therapeu-tic range when the dosage was based on lean bodyweight alone, and 1 patient had a peak level of 14.0,ug/ml. This method of calculating dosage tended tooverestimate the dosages these patients with renal in-sufficiency needed, since half of the patients had peakconcentrations above the therapeutic range and onlyone had a peak level below this range. After individual-ization of therapy 7 of the 10 patients had peak levelswithin the therapeutic range. Of the other three pa-tients who had unstable renal insufficiency: one, witha peak concentration of 12.0 ug/ml, had an importantdeterioration of his renal function during the studyperiod, the creatinine clearance dropping from 29 to2 ml/min; in the other patient, with a peak concentra-tion of 3.7 ,g/ml, renal function gradually improvedduring the study period, the creatinine clearance in-creasing from 5 to 22 ml/min. The remaining patienthad stable renal insufficiency (creatinine clearance 41ml/min) but a potentially toxic peak concentration ofgentamicin (14.0 ,ug/ml)- before individualization oftherapy; afterwards, however, the concentration fell tothe safe peak of 3.4 ,ug/ml.

In group 3 the mean change in dose was 30 mg(minimum 10, maximum 80 mg) and the mean changein dosing interval 11.2 hours (minimum 2, maximum46 hours).To rule out drug accumulation and measure the

reproducibility of the peak and trough serum levelsof gentamicin with the use of individual pharmacokin-etic parameters for each patient we monitored the se-rum levels for up to 12 days in four patients withnormal renal function. The levels remained in thetherapeutic range and varied by only 1 ug/ml fromthe original concentration obtained on the basis of theindividual pharmacokinetic parameters.

Discussion

The poor predictability of serum concentrations ofgentamicin resulting from regimens calculated solelyon the basis of total body weight, even in absence ofrenal insufficiency, has been stressed in the litera-ture48'10 and is confirmed in the present study. Whenthis method was used approximately one patient infive received an inadequate dosage of the drug. Thetendency for physicians to give inadequate dosages ofgentamicin has been observed by others."

Although the Hull lean body weight nomogram"

predicts the serum concen.tration of gentamicin muchmore accurately, as shown by Russell and colleagues14in patients who had undergone an operation, some

patients' serum levels are still likely to fall outside thetherapeutic range, particularly if renal failure is pres-

ent. Our study confirms that giving gentamicin withoutmeasuring its serum levels is, at best, chancy.

Physicians fortunate enough to practise in a settingin which measurement of serum levels of gentamicinis available are faced with a choice in individual cases:

they can obtain an occasional blood sample and, fromits gentamicin level, "guesstimate" the alteration indosage that would bring the patient's serum concentra-tion closer to the desired level; or, using a computerand multiple serial blood samples taken in the intervalbetween two infusions, they can calculate the appro-

priate dosage for the patient, as has been done withsuccess by Sawchuk and associates."',"The first method has the advantage of being simple

but the disadvantage of depending largely upon ex-

perience. Although the seasoned prescriber of genta-micin would become quite good at this method, theneophyte might have difficulty adjusting the doses anddosing intervals. Although the second method is quiteimpressive and precise, it has the inconvenience ofdepending upon multiple, precisely timed blood samplesand computer hardware, which is not universally avail-able. Thus, in our opinion there was a definite needfor a simple technique that would give the physiciana reasonably accurate estimate of the drug's half-lifeand volume of distribution in each patient, as well as

recommendations on the dosage necessary to obtainthe desired serum level. In this study we used a methodthat requires only two blood samples for determiningthe peak and trough serum gentamicin concentrations.This eliminates the need for nurse attendance and re-

peated blood sampling between gentamicin infusions.

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Table II-Mean peak and trough serum gentamicin concentrations before and after individualization of therapy

Serum gentamicin concentration (Vg/ml);mean + SD (plus minimum & maximum levels)

Group 1 Group 2 Group 3

Level Before After Before After Before After

Peak 5.0 + 1.6 6.7 i 1.4 7.0 ± 2.3 6.3 + 1.2 8.7 i 3.1 6.2 2.6(1.8 & 9.8) (4.0 & 9.4) (4.1 & 16.0) (4.2 & 8.4) (3.9 & 14.0) (3.4 & 12.0)

Trough 0.8 + 0.6 1.3 0.7 0.9 -+i 0.6 1.2 + 0.8 3.1 + 1.5 1.9 1.5(0.1 & 2.5) (0.3 & 3.6) (0 & 2.4) (0.2 & 3.2) (1.1 & -8.0) (0.4 & 4.4)

Furthermore, the pharmacokinetic calculations werecarried out on a pocket-sized programmable calculatorwhose cost is well within the reach of most hospitals'budgets. This simplified method makes pharmacoki-netic studies in individual patients clinically feasible.Two recent papers have described the use of the

programmable hand-held calculator in carrying outpharmacokinetic analysis.16'17 However, the authors of-rered only a theoretical discussion of possible computerprograms and did not describe the results of theirapplied use. Furthermore, they did not design a programthat would allow the adjustment of an aminoglycosidedosage schedule once the patient's pharmacokineticparameters were known.When the patients in our study had their gentamicin

dosage adjusted according to their individual pharma-cokinetic data, all subsequently had serum levels withinthe therapeutic range, and 46% had levels withinI .g/ml of the peak concentration desired. This com-pares favourably with the results of Sawchuk and as-sociates' complex method, with which 60% of thepeak values were within 1 .g/ml of those predicted.13The trough serum concentrations were also reliablypredicted by our method, 88% falling within 1 .g/m1of the levels desired.

The predictive value of the lean body weight nomo-gram in our patients with normal renal function wasgood, except in one patient, who had a toxic peakserum concentration of gentamicin (16.0 .g/ml). Allthe other patients had therapeutic peak concentrations.Thus, the use of this nomogram was superior to meth-ods of calculating dosage that are based solely on totalbody weight. These results agree with those of Russelland colleagues,14 who demonstrated the applicabilityof the Hull nomogram. However, only the use of in-dividual pharmacokinetic data resulted in therapeuticpeak concentrations in all our patients with normalrenal function, and only this method eliminated theoccurrence of possibly toxic blood levels.

Pharmacokinetic studies in individual patients areeven more desirable in those with renal insufficiency.Of our 10 patients with renal insufficiency 6 had peakserum levels of gentamicin that were outside the thera-peutic range when the Hull nomogram was used; thelevels were considerably improved by the use of indi-vidual pharmacokinetic data. Worsening renal insuf-ficiency explained the peak concentrations that re-mained above the therapeutic range, and improvingrenal function explained those that remained belowthe therapeutic range. These results underscore theneed for individual pharmacokinetic studies in all pa-tients with renal insufficiency, and for dose-to-dosemonitoring in those with unstable insufficiency. Weagree with Hull and Sarubbi11 that management of suchpatients should include repetitive determination of theserum level of gentamicin.

It is important to obtain therapeutic serum levels ofgentamicin in patients with burns. In one hospital,after the introduction of individualized aminoglycosidetherapy the overall mortality in these patients droppedfrom 15.8% to 8.2%, and the mortality in those withseptic burns from 62% to 33% *18

Although the professional pharmacokineticist mightbe somewhat disturbed by the use of a one-compart-ment model for a drug that is actually distributed inat least two compartments, it has to be understoodthat the object of our study was not to redefine thepharmacokinetics of gentamicin but rather to validatea technique that would help clinicians adjust genta-micin dosage schedules. The fact that the gentamicinhalf-life and volume of distribution in patients withnormal renal function estimated with our techniquecorrespond to those that have been reported in theliterature should provide some reassurance. Further-more, Chow and coworkers19 have successfully pre-dicted serum levels of gentamicin using a one-compart-ment open linear pharmacokinetic model with a pro-grammable hand-held calculator and thus confirmedthis model's validity. However, those authors predictedthe gentamicin levels from an assumed volume of dis-tribution and half-life, not from pharmacokinetic datafor individual patients.

In conclusion, the simplified method involving in-dividual pharmacokinetic data that we have describedresults in excellent predictability of serum concentra-tions of gentamcin. In patients with normal renal func-tion increasing predictability is obtained with dosageestimations based on total body weight, the lean bodyweight nomogram and pharmacokinetic data for theindividual patient, but only the last method results intherapeutic serum concentrations of the drug in allpatients. In patients with renal insufficiency the nomo-gram is inadequate but predictability is good whenindividual pharmacokinetic studies are done; dose-to-dose monitoring must be done in those with unstablerenal insufficiency. Individual pharmacokinetic studiesshould now be more feasible and more widespread,and thus we should see improving therapeutic efficacyand decreasing morbidity and mortality in thesepatients.We thank Claudette Lamoureux. Monique Pharand andDoris Roy for carrying out the gentamicin radioimmuno-assays. and the staff physicians, residents and nurses ofH6tel-Dieu de Montr6al for their patience and under-standing, without which this work would not have beenpossible.

This study was supported in part by a grant from theCanadian Society for the Progress of Clinical Pharma-cology and Therapeutics. and by the MacDonald-StewartFoundation.

References1. APPEL GB, NEU HC: Gentamicin in 1978. Ann internMed 1978; 89: 528-538

2. JACKSON GG, RIFF U: Pseudomonas bacteremia: pharma-cologic and other bases for failure of treatment withgentamicin. J infect Dis 1971; 124 (suppl): 5185-S191

3. HEwrrr WL: Reflections on the clinical pharmacology ofgentamicin. Acta Pathol Micro biol Scand [B] 1973; 81(suppl 241): 151-156

4. NOONE P, PARSONS TMC, PATTISON JR, SLACK RCB,GARFIELD-DAVIES D, HUGHES K: Experience in monitoringgentamicin therapy during treatment of serious gram-negative sepsis. Br Med J 1974; 1: 477-481

5. DAHLGREN JG, ANDERSON ET, HEwIrT WL: Gentamicinblood levels: a guide to nephrotoxicity. A nti,nicrob AgentsChernother 1975; 8: 58-62

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6. JACKSON GG, ARCIERI G: Ototoxicity of gentamicin inman: a survey and controlled analysis of clinical experi-ence in the United States. J Inject Dis 1971; 124 (suppl):5130-5137

7. SCHULTZE RG, WINTERS RE, KAUFFMAN H: Possiblenephrotoxicity of gentamicin. Ibid: 5145-5147

8. KAYE D, LEVISON ME, LABOVITZ ED: The unpredictabil-ity of serum concentrations of gentamicin: pharmacoki-netics of gentamicin in patients with normal and abnormalrenal function. J Infect Dis 1974; 130: 150-154

9. MCHENRY MC, GAVAN TL, GIFFORD RW JR, GEURKINKNA, VAN OMMEN RA, TOWN MA, WAGNER JG: Genta-micin dosages for renal insufficiency. Adjustments basedon endogenous creatinine clearance and serum creatinineconcentration. Ann Intern Med 1971; 74: 192-197

10. BARZA M, BROWN RB, SHEN D, GIBALDI M, WEINSTEINL: Predictability of blood levels of gentamicin in man.J Infect Dis 1975; 132: 165-174

11. HULL JH, SARUBBI FA JR: Gentarnicin serum concentra-tions: pharmacokinetic predictions. Ann interll Med 1976;85: 183-189

12. SAWCHUK RJ, ZASKE DE: Pharmacokinetics of dosingregimens which utilize multiple intravenous infusions:gentamicin in burn patients. J Pharmacokinet Biopharm1976; 4: 183-195

13. SAWCHUK RJ, ZASKE DE, CIPOLLE RJ, WARGIN WA,STRATE RG: Kinetic model for gentamicin dosing with

the use of individual patient parameters. Clin PharmacolTher 1977; 21: 362-369

14. RUSSELL WL, MCNEELY DJ, YOST RL, O'LE.Y JP: Con-firmation of a computer-derived nomogram to predictgentamicin serum concentrations in postsurgical patients.Am J Hosp Pharm 1978; 35: 570-574

15. ZASKE DE, STRATE RG, SOLEM LD, CIPOLLE RJ, KING-STON RL: Individualized aminoglycoside therapy based onpharmacokinetic analysis. Scientific exhibit presented atSixty-Third Annual Clinical Congress of the AmericanCollege of Surgeons, Dallas, Oct 17-21, 1977

16. FOSTER TS, BOURNE DWA: Use of a programmable hand-held calculator for clinical pharmacokinetics. Am J HospPharm 1977; 34: 70-75

17. Buicn RG: The programmable hand-held calculator. Apowerful tool in clinical pharmacokinetics. Drug intellClin Pharm 1979; 13: 328-333

18. ZASKE DE, STRATE RG, SOLEM LD, CIPOLLE RJ, KING-STON RL: Increased patient survival and decreased toxicitywith individualized aminoglycoside therapy. Scientific ex-hibit presented at Sixty-Third Annual Clinical Congressof the American College of Surgeons, Dallas, Oct 17-21,1977

19. CHOW M, DEGLIN J, HARRALSON A, BARTLETT R, QUIN-TILIANI R: Prediction of gentamicin serum levels usinga one-compartment open linear pharmacokinetic model.Am J Hosp Pharm 1978; 35: 1078-1081

Lobar pneumonia caused by Mycoplasma pneumoniaeDONALD W. COCKCROFT, MD, FRC P[C]; GREGORY A. STILWELL,* MD, FRCP[C]

Seven patients with Mycoplasma pneumoniae pneumoniapresented with moderate to dense consolidation in one (infive patients) or more lobes. The diagnosis was suspectedin five patients after failure to respond to I to 6 (average2.6) antibiotics administered for 2 to 12 (average 7) days,and in one patient upon the development of hemolytic ane-mia. Clues to the diagnosis of nonbacterial pneumonia in-cluded a nonrespiratory viral-like prodromal period (in five),a nonproductive cough (in five), lack of rigors (in seven),recent .'pneumonia" in family members (in three), normaltotal leukocyte and neutrophil counts (in six) and the ab-sence of bacterial pathogens in smears and cultures ofsputum (in all seven). The diagnosis of M. pneumoniaeinfection was supported by the presence of cold agglutinins(in a titre of I £4 or greater) in the serum of five or sixpatients and was confirmed by diagnostic levels or increasesin the titre of M. pneumoniae complement fixing antibodies.Awareness of the fact that M. pneumoniae can present aslobar consolidation and close attention to the clinical andlaboratory data can usually suggest a nonbacterial causeand thus prevent delay in appropriate antibiotic treatment.

Sept malades souffrant de pneumonie a Mycoplasma pneu-moniae ont ete admis avec une image de consolidationmoderee A dense d'un (chez cinq sujets) ou plusleurs lobes.Chez cinq patients le diagnostic a ete soup9onne apres

From the departments of medicine and microbiology,University Hospital, Saskatoon*Deceased

Reprint requests to: Dr. Donald W. Cockcroft, Divisionof pulmonary medicine, University Hospital, Saskatoon,Sask. S7N OXO

l'echec de I a 6 antibiotiques (2.6 en moyenne) adminis-tres pour des periodes de 2 a 12 jours (moyenne do 7) ot,chez une patiente, par l'apparition d'une an6mie h6moly.tique. Los indices menant au diagnostic do pneumonie nonbacterienne inclualent un prodrome d'infection non respira-toire do type viral (chez cinq), une toux secho (choz cinq),l'absence do frissons (choz sept), uno "pneumoni&' recentechez des membres do leur famille (choz trois), une num6-ration leucocytaire ot un taux des polynucleairos noutro-philes normaux (choz six) ot l'absence do bacterios patho-genes dans los frottis ot los cultures do crachats (chez lossept sujots). Le diagnostic d'infection a M. pneumoniae aete etaye par Ia pr6sence d'agglutinines froidos (a un titrod'au moms 1:64) dans le serum do cinq patients sur six, etii a ete confirme par des taux do signification diagnostiqueou des elevations du titre dos anticorps anti-M. pneumoniaefixant le complement. Une prise do conscience du fait quoM. pneumoniae pout so manifester sous Ia forme d'uneconsolidation lobaire ot une attention minutiouse aux r6sul-tats dos examons cliniquos ot do laboratoire peuvont habi-tuellement suggeror une cause non bacterienne ot, enconsequence, prevonir tout d6lai dans Ia mise on routo d'untraitement antibiotique appropri6.

Pneumonia caused by Mycoplasma pneumoniae iscommon;1 frank lobar consolidation, however, is statedto be rare2 or infrequent.3 We encountered seven pa-tients in an 18-month period who had M. pneumoniaelobar pneumonia. Because of moderate to dense lobarconsolidation the diagnosis was not suspected in sixand appropriate antibiotic therapy was delayed. Areview of the seven cases showed that the clinical andlaboratory data suggested nonbacterial pneumonia inall the patients.

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