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Summary ANTIMICROBIAL AGENTS ANTIMICROBIAL AGENTS Summary of a Round Table Discussion By Mark H. Lepper, M.D., and Harris D. Riley, Jr., M.D. Department of Preventive Medicine, University of Illinois (M.H.L.), and Department of Pediatrics, University of Oklahoma (H.D.R.) NTIMKROBIAL agents have had an espe- sistance of the host to infection. (The effect cially great impact in pediatrics. Al- of cortisone on stneptococcal infections in though many diseases have been conquered the rabbit was cited : 58 out of 66 rabbits easily with proper antimicrobial therapy, pnetreated with cortisone died; 5 of 60 con- there still remain difficulties and failures. trol animals died.) Instances of empyema Dr. Leppen opened the session with a dis- developing during treatment of pneuimo- cussion of some of the failures of antimi- coccal pneumonia with both antibiotics and crobial therapy. ACTH were described. The discussants agreed that at no time should adrenal con- HYPERACUTE INFECTIONS ticosteroids be used in the treatment of in- Hyperacute infections, i.e., infections fectious processes without simultaneoums ad- which are often fatal within 24 hours from ministration of adequate amounts of appro- the onset of symptoms, and resistant strains pniate antibiotics. of organisms, account for the vast majority Dr. Lepper reviewed some of the salient of failures in the use of antibiotics. A few facts in connection with the use of cortisone cases cannot be classified into either cate- and allied substances in the treatment of gory and remain as unexplained failures. overwhelming infections, including menin- The magnitude of the problem of hypen- gococcemia and the Waterhouse-Fnidenich- acute infections can be judged by the fact sen syndrome. In the period before conti- that in a contagious disease hospital about sone was readily available, it was used in a third of the fatalities from nontubercu- half of all such patients who died (death bus, bacterial infectious diseases occur rate, 5%). With the liberal umse of cortisone within the first 24 hours from the onset of between 1952 and 1954, there was no dem- symptoms. Meningitis due to meningococ- onstrable change in the death rate from cus on pneumococcus, or meningococcemia, overwhelming infections. Then, because of are most commonly encountered in this the danger of superimposed infection, the group. In Dr. Lepper’s experience, those use of cortisone was restricted-again with- patients who will die within 24 hours from out a change in the death rate. For the pa- onset of symptoms can be predicted early tients treated with cortisone, the death from clinical observations, and they com- rates in these three periods were: 100, 81 mand “heroic therapy.” and 100%, respectively. A lively discussion of the use of adrenal In an effort to elucidate more subtle dif- corticosteroids as pant of “heroic therapy” ferences which might occur from the use in hyperacute infections ensued. Dr. Riley of cortisone, Dr. Lepper conducted con- pointed out that they are useful agents but trolled studies with four types of meningi- have serious side effects and definite haz- tis : Hemophilus influienzal, meningococcal, ards. They are known to decrease the re- pneumococcal, and tuberculous. In 57 pa- Presented at the Annual Meeting of the American Academy of Pediatrics, October 20, 1958. Summary prepared by Margaret Lyman, M.D. ADDRESS: (M.H.L.) Department of Preventive Medicine, University of Illinois, 840 S. Wood Street, Chicago 12, Illinois. PEDIATRICS, June 1959 1192 Downloaded from www.aappublications.org/news by guest on September 26, 2021 AMERICAN ACADEMY OF PEDIATRICS - PROCEEDINGS 1193 tients with H. influenzae meningitis, 28 re- DR. LEPPER: This has not been demon- ceived cortisone, 29 did not. Tile only dif- strated. I do not believe cortisone is mdi- ference noted was a significantly greater Cate(1 routinely in the treatment of tiliS ds- imlcidence of sui)dumral effusions in those Pa- ease. tients who received cortisone. From this it Q UESTION: What is the mechanism of ac- was concluded that cortisone is not imidi- tion of steroids in infections? cated as an adjumnct in the treatment of H. DR. LEPPER: The fundamental action is influenzae meningitis. Of 56 patients with not known, but they suppress the inflam- meningococcal meningitis, half received matory response which is one mechanism cortisone (7 patients with Waterhouse-Fnid- of defense. With long-term use of steroids, enichsen syndrome were excluded from this there will usually be a decrease in the pa- group) and half did not. No significant tient’s antibody titer. difference could be detected in the two Q UESTION: With the decrease in antibody groups. In the patients with Waterhouse- titer, will there be an increase in the rate Fnidenichsen syndrome, all received sten- of recurrence of infections? oids; the mortality rate was comparable to DR. LEPPER: In our series, there was no that given in the literature. Dr. Lepper statistically significant difference in tile re- noted that none of these patients had evi- currence rate; however, cortisone was not dence of adrenal insufficiency after re- used for long enough periods of time to covery. In the group with pneuimococcal demonstrate reduced antibody titers. meningits, 14 patients received steroids, Q UESTION: What dosages of steroids were 14 did not. There was one death in each used? group; the value of steroids was not estab- DR. LEPPER: Hydnocortisone, 2.5 mg/kg lished for this disease. Similarly in tuber- intravenously, for 5 days. Decreasing doses culous meningitis, it was difficult to estab- were then used for 3 days, and ACTH was lish definite value for the use of the sten- given intramuscularly for 2 days prior to oids. cessation of all steroid therapy. The requiirement of large nummbers of Q UESTION: The New England Journal of cases of any given disease to demonstrate Medicine (258:639, March 27, 1958) ne- small differences was stressed. A current cently reported a series of patients with study in five centers, using double-blind meningococcemia treated with steroids and technique, may prove helpful. The group concluded that there was no good reason was cautioned against generalizing from for their use in this disease. What is your one infection to another, or from one form comment on this report? of tubenculous infection to another. They DR. LEPPER: I am inclined to agree with were urged to avoid the routine use of the authors; however, considerable pres- adrenal steroids in serious infections; to se- sure will be brought to bean to use the lect the patients who are to receive sten- steroids in this disease because of its high oids carefully; and to avoid the rationali- fatality rate. I believe at present that cniti- zations of “maybe I can get away with it” cism will be greater if it is not used than and “it doesn’t seem to do any harm.” if it is. The present literature does not Q UESTION: Has the use of adrenal ster- contain satisfactory evidence for not using oids in acute laryngotracheobronchitis low- steroids in meningococcemia. ered the incidence of tracheotomy? RESISTANT ORGANISMS DR. LEPPER: To my knowledge, there is no study available with sufficient numbers The second factor responsible for failures of patients upon which to base an opinion. in antibiotic therapy, strains of organisms Q UESTION: Is there more likelihood of re- resistant to available agents, was discussed current laryngotnacheobnonchitis when con- primarily by Dr. Harris Riley. Some or- tisone is used? ganisms are naturally resistant and some, Downloaded from www.aappublications.org/news by guest on September 26, 2021 1194 ANTIMICROBIAL AGENTS while predominantly sensitive, may develop growth of resistant organisms. Or, supenim- resistance. The premature or young infant, posed infection may occumn from exogenoums the extremely old patient, or some under- spread, such as may be produmced by im- lying serious disease predisposing to infec- proper catheterization during the diagnosis tion, share, in common, characteristics of of urinary tract disease. A genuine super- the host which favor infections by resistant imposed infection was not noted by Dr. strains of organisms. Some antimicrobial Lepper in a series of nine patients with in- agents eradicate sensitive strains, allowing dwelling catheters when multiple cultures resistant ones to grow; thus treatment itself were obtained before treatment was started. may produce resistant strains. Dr. Leppen Thus, in these nine patients, all had mixed illustrated this with a brief discussion of the infections which could be misinterpreted as staphylococcus : The per cent of all staphy- superimposed infections. He concludes that lococci resistant to erythromycin rose rap- probably infections of the genito-urimlary idly soon after it became widely used, while tract have a mixture of organisms at the on- the pen cent resistant to penicillin slowly set of therapy more often than is commonly decreased. However, when erythromycin appreciated. Thus, it is essential to treat the was used less abundantly, there was a rapid patient, not the bacteria, for the patient decline in the per cent of resistant strains may well tolerate one organism better than at first, and then the per cent resistant, just another which may emerge as the resuilt of as with penicillin, has declined much more therapy. slowly. The “back-mutation” rate varies Q UESTION : How much reliance do you! with different antibiotics but it would prob- place on laboratory determination of sensi- ably take many years for staphylococci to tivity of various organisms to different anti- become sensitive to most antibiotics once biotics? again if their use were discontinued. DR. LEPPER: There are many variables in Considerable variation in the degree of the determination of resistance and sensi- resistance of staphylococci will be found in tivity. The present disc method is highly different hospitals and in different commu- variable but efforts are being made to nities.
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