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A new look at diabetes mellitus and infection
DECEMBER 1970
The
American
Journal
of Surgery VOLUME 120 NUMBER 6
EDITORIALS
A New Look at Diabetes Mellitus and Infection MARTIN C. ROBSON, MD, MC, USA, Seoul, Korea
The question of w h e t h e r patients with diabetes me]litus have a propensity f o r surgical infection is debatable. Until recently the clinical impression has been t h a t they have, although experimental evidence has not been conclusive. Evidence has now been accumulated which challenges the concept that the presence of diabetes metlitus p e r sc lowers the resistance of a host to infection. Using q u a n t i t a t i v e bacteriologic studies, it has been shown t h a t infection results f r o m contamination when there are more than 100,000 organisms present per g r a m of tissue or p e r milliliter of biologic fluid. This a p p e a r s to be t r u e regardless of the presence or absence of diabetes mellitus, cancer, steroid medication, or o t h e r f a c t o r s which are believed to decrease host resistance. However, the speed and ease with which a given inoculum reaches the critical level of 100,000 o r g a n i s m s m a y well be affected by factors influencing host. resistance. We have studied this problem in relation to the blood glucose l e v e l at the time of clinical infection. In a retrospective study of 214 patients with septicemia, it was found t h a t 81 p e r cent of patients with sepsis, h a v i n g a blood glucose level of less than 110 mg per cent on the day blood culture gave p o s i t i v e results, had a g r a m , n e g a t i v e organism septicemia, w h e r e a s 82 per cent of patients whose blood glucos e w a s g r e a t e r t h a n 130 m g p e r cent h a d gram-positive organisms o n blood cult u r e [1]. Similarly, i n : V i t r o g r o w t h studies of bact e r i a in glucose-supplemented plasma revealed t h a t the g r o W t h of g r a m - n e g a t i v e o r g a n i s m s was' From the Department of Surgery, Seoul Military Hospital (Prov), Seoui, Korea. Volume 120, December 1970
inhibited by high levels of glucose [2]. Conversely, gram-positive bacteria a p p e a r e d to t h r i v e on hyperglycemia. Keeping in mind the difference ill effects of hyperglycemia on g r a m - n e g a t i v e and gram-positive bacterial surviwd, we reviewed reported experimental and clinical studies involving various types of surgical infections in diabetic animals and human subjects. Many . a b p a r e n t contradictions in tile l i t e r a t u r e r e g a r d i n g an increase or decrease in the incidence of infectious complications in diabetic patients were immediately clarified. It becomes obviou,s t h a t any increased incidence of infection m a y be due to the abnormal blood glucose level r a t h e r than to any p r e d e t e r m i n e d genetic coding specific f o r diabetes meltitus. The question t h a t r e m a i n s is how the surgeon m i g h t put this i n f o r m a t i o n to use when t r e a t i n g patients with diabetes mellitus. Because an abnormal blood glucose level affects the speed and ease of c o n t a m i n a t i o n resulting in clinical infection. early t r e a t m e n t is essential. I f a diabetic pat i e n t presents in the e m e r g e n c y ward with a surgical infection, a blood glucose level can be obtained within minutes. Empirical t r e a t m e n t against e i t h e r gram-positive or g r a m - n e g a t i v e organisms can be instituted p r i o r to obtaining the c u l t u r e r e p o r t w i t h ml 80 per cent chance of selecting the p r o p e r bacterial s t a i n i n g group. Theoretically, patient,s with h y p e r g l y c e m i a should be treated with a combination of antibacterial agents which include a bactericidal a g e n t effective a g a i n s t gram-positive organisms. On the o t h e r hand, with blood glucose levels u n d e r 110 m g p e r cent, the a r m a m e n t a r i u m would wisely include a g r a m - n e g a t i v e bactericidal drug, T h i s ~t
Editorial
~egimen has proved most helpful in patients with low blood glucose levels and infections. Because m a n y a n t i b a c t e r i a l agents which are highly effective against gram-negative organisms have severe side effects, there has been a hesitancy ?to use these agents without culture evidence of ia igramnegative infection. When the glucose level i s less t h a n 110 mg per cent, one can be reasonably confident t h a t a gram-negative organism is t h e etiologic agent. The same reasoning can be used in the postoperative patient with diabetes mellitus who manifests an infection or sepsis. Again, early t r e a t m e n t is i m p o r t a n t and the blood glucose level is useful in determining which d r u g is to be used initially. In our laboratory, other studies b a s e d on b a c terial quantification have revealed t h a t most surgical infections are due to a single r a t h e r t h a n multiple bacterial species [3]. This allows the use of a single antibacterial agent with a g r e a t e r degree
682
of safety. Keeping in mind the information on blood glucose levels, we have been evaluating the initial use of sodium cephalotl!in in diabetic patients presenting w i t h an undiagnosed infection and having a blood glucose level of more than 130 mg per cent. K a n a m y c i n sulfate has been chosen f o r those patients with a blood glucose level of less than 110 rag per cent at the time o f suspected infection. Sufficient data have not been accumulated to recommend this protocol, but to date it appears t ~ a t early control of the infection h a s been obtained. References 1. Robson MC, Heggers JP: Variables in host resistance pertaining to septicemia. I. Blood glucose level. J Amer Geriatrics Soc 17: 991, 1969. 2. Robson MC, Heggers JP: Effect of hyperglycemia on survival of bacteria. SurgForum 20: 56, 1969. 3. Robson MC, Heggers JP: Surgical infection. I. Single bacterial species or polymicrobic in origin? Surgery 65: 608, ]969.
The American Jouma! of SurlKery
The
American
Journal
of Surgery VOLUME 120 NUMBER 6
EDITORIALS
A New Look at Diabetes Mellitus and Infection MARTIN C. ROBSON, MD, MC, USA, Seoul, Korea
The question of w h e t h e r patients with diabetes me]litus have a propensity f o r surgical infection is debatable. Until recently the clinical impression has been t h a t they have, although experimental evidence has not been conclusive. Evidence has now been accumulated which challenges the concept that the presence of diabetes metlitus p e r sc lowers the resistance of a host to infection. Using q u a n t i t a t i v e bacteriologic studies, it has been shown t h a t infection results f r o m contamination when there are more than 100,000 organisms present per g r a m of tissue or p e r milliliter of biologic fluid. This a p p e a r s to be t r u e regardless of the presence or absence of diabetes mellitus, cancer, steroid medication, or o t h e r f a c t o r s which are believed to decrease host resistance. However, the speed and ease with which a given inoculum reaches the critical level of 100,000 o r g a n i s m s m a y well be affected by factors influencing host. resistance. We have studied this problem in relation to the blood glucose l e v e l at the time of clinical infection. In a retrospective study of 214 patients with septicemia, it was found t h a t 81 p e r cent of patients with sepsis, h a v i n g a blood glucose level of less than 110 mg per cent on the day blood culture gave p o s i t i v e results, had a g r a m , n e g a t i v e organism septicemia, w h e r e a s 82 per cent of patients whose blood glucos e w a s g r e a t e r t h a n 130 m g p e r cent h a d gram-positive organisms o n blood cult u r e [1]. Similarly, i n : V i t r o g r o w t h studies of bact e r i a in glucose-supplemented plasma revealed t h a t the g r o W t h of g r a m - n e g a t i v e o r g a n i s m s was' From the Department of Surgery, Seoul Military Hospital (Prov), Seoui, Korea. Volume 120, December 1970
inhibited by high levels of glucose [2]. Conversely, gram-positive bacteria a p p e a r e d to t h r i v e on hyperglycemia. Keeping in mind the difference ill effects of hyperglycemia on g r a m - n e g a t i v e and gram-positive bacterial surviwd, we reviewed reported experimental and clinical studies involving various types of surgical infections in diabetic animals and human subjects. Many . a b p a r e n t contradictions in tile l i t e r a t u r e r e g a r d i n g an increase or decrease in the incidence of infectious complications in diabetic patients were immediately clarified. It becomes obviou,s t h a t any increased incidence of infection m a y be due to the abnormal blood glucose level r a t h e r than to any p r e d e t e r m i n e d genetic coding specific f o r diabetes meltitus. The question t h a t r e m a i n s is how the surgeon m i g h t put this i n f o r m a t i o n to use when t r e a t i n g patients with diabetes mellitus. Because an abnormal blood glucose level affects the speed and ease of c o n t a m i n a t i o n resulting in clinical infection. early t r e a t m e n t is essential. I f a diabetic pat i e n t presents in the e m e r g e n c y ward with a surgical infection, a blood glucose level can be obtained within minutes. Empirical t r e a t m e n t against e i t h e r gram-positive or g r a m - n e g a t i v e organisms can be instituted p r i o r to obtaining the c u l t u r e r e p o r t w i t h ml 80 per cent chance of selecting the p r o p e r bacterial s t a i n i n g group. Theoretically, patient,s with h y p e r g l y c e m i a should be treated with a combination of antibacterial agents which include a bactericidal a g e n t effective a g a i n s t gram-positive organisms. On the o t h e r hand, with blood glucose levels u n d e r 110 m g p e r cent, the a r m a m e n t a r i u m would wisely include a g r a m - n e g a t i v e bactericidal drug, T h i s ~t
Editorial
~egimen has proved most helpful in patients with low blood glucose levels and infections. Because m a n y a n t i b a c t e r i a l agents which are highly effective against gram-negative organisms have severe side effects, there has been a hesitancy ?to use these agents without culture evidence of ia igramnegative infection. When the glucose level i s less t h a n 110 mg per cent, one can be reasonably confident t h a t a gram-negative organism is t h e etiologic agent. The same reasoning can be used in the postoperative patient with diabetes mellitus who manifests an infection or sepsis. Again, early t r e a t m e n t is i m p o r t a n t and the blood glucose level is useful in determining which d r u g is to be used initially. In our laboratory, other studies b a s e d on b a c terial quantification have revealed t h a t most surgical infections are due to a single r a t h e r t h a n multiple bacterial species [3]. This allows the use of a single antibacterial agent with a g r e a t e r degree
682
of safety. Keeping in mind the information on blood glucose levels, we have been evaluating the initial use of sodium cephalotl!in in diabetic patients presenting w i t h an undiagnosed infection and having a blood glucose level of more than 130 mg per cent. K a n a m y c i n sulfate has been chosen f o r those patients with a blood glucose level of less than 110 rag per cent at the time o f suspected infection. Sufficient data have not been accumulated to recommend this protocol, but to date it appears t ~ a t early control of the infection h a s been obtained. References 1. Robson MC, Heggers JP: Variables in host resistance pertaining to septicemia. I. Blood glucose level. J Amer Geriatrics Soc 17: 991, 1969. 2. Robson MC, Heggers JP: Effect of hyperglycemia on survival of bacteria. SurgForum 20: 56, 1969. 3. Robson MC, Heggers JP: Surgical infection. I. Single bacterial species or polymicrobic in origin? Surgery 65: 608, ]969.
The American Jouma! of SurlKery