Postoperative Infections: Current Concepts

Postoperative Infections: Current Concepts From the Departments of Surgery, Massachusetts Memorial Hospitals and Boston University School of Medicine

CHESTER W. HOWE, M.D. Visiting Surgeon; Associate Professor of Surgery

PETER J. MOZDEN, M.D. Assistant Visiting Surgeon; Assistant Professor of Surgery

the period 1950-1961 at the Massachusetts Memorial Hospitals there were 15,658 major surgical procedures on the general surgical service,* and 1909 postoperative complications in 1285 patients. Seven hundred sixty-eight (40 per cent) of these complications were due to infections as shown in Table 1. It is the purpose of this paper to discuss certain factors relevant to the understanding and management of these complications based upon some observations in the surgical literature which are considered currently important in the light of our own experience. Attention will be directed mainly toward wound infections, since they predominate as infectious complications in our series, but most concepts expressed are applicable to other types of postoperative infection as well. DURING

GENERAL CONSIDERATIONS WITH PARTICULAR REFERENCE TO POSTOPERATIVE WOUND INFECTIONS

The Susceptible Host

There is an increasing awareness among surgeons of the importance of Supported in part by research grant E-2098 (C1, C2, C3) from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, United States Public Health Service. * Excludes genitourinary and gynecological surgery. Includes neurosurgery, orthopedics and a few thoracic cases.

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Table 1.

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Postoperative Infectious Complications Following 15,658 Major Operations* TYPES OF INFECTION

NUMBER

Wound (350 major, 117 minor) ................ 467 Pulmonary .................................. 157 Pneumonia. . . . . . . . . . . . . . . . . . . . .. 92 Atelectasis. . . . . . . . . . . . . . . . . . . . .. 56 Empyema....................... 6 Tracheobronchitis. . . . . . . . . . . . . . .. 2 Lung abscess. . . . . . . . . . . . . . . . . . .. 1 Miscellaneous .............................. " 144 Abscesses Intra-abdominal and pelvic .... 48 Soft tissuet. . . . . . . . . . . . . . . . .. 15 Brain........ ............ ... 1 Genitourinary infections .......... 31 Peritonitis. . . . . . . . . . . . . . . . . . . . . .. 18 Septicemia and bacteremia. . . . . . .. 12 Parotitis. . . . . . . . . . . . . . . . . . . . . . .. 4 Staphylococcal enteritis. . . . . . . . . .. 3 Furunculosis. . . . . . . . . . . . . . . . . . . .. 2 Meningitis. . . . . . . . . . . . . . . . . . . . .. 2 Septic embolus. . . . . . . . . . . . . . . . . .. 2 Gas gangrene. . . . . . . . . . . . . . . . . . .. 1 Pyodermia. . . . . . . . . . . . . . . . . . . . .. 1 Bacteremic cholangitis. . . . . . . . . . .. 1 Tenosynovitis. . . . . . . . . . . . . . . . . . .. 1 Oral moniliasis. . . . . . . . . . . . . . . . . .. 1 Infected sinus tract. . . . . . . . . . . . . .. 1 TOTAL INFECTIONS. • • . . . . . . . . . . . • . . . . . • . • . . .•

768

* From weekly house officers' service reports. Not compiled with predetermined criteria or research-type statistical standards. Wound infection data probably are more accurate owing to increased awareness because of research being carried out in this area. There were 14,279 A and B cases considered as clean, and 1,379 C cases considered as infected according to previously published criteria." t Includes 2 flank and 2 ischiorectal abscesses. those determinants of postoperative infection which reside within the patients themselves, as compared to those concerned with the type or density of the bacterial populations in the hospital environment. Advances in medicine and surgery have resulted in extensive operations upon more patients with degenerative and metabolic diseases who are infection-susceptible. But more important than this are the "primary lodgment" concept of Miles and his associates,81, 82, 83 and the experiments of Elek and Conen,39 Dubos35 and others. These workers have demonstrated that changes in the defenses of a healthy host resulting in infection can be rapidly induced by methods having effects similar to many commonly used medical and surgical practices. By causing cardiovascular shock (intraperitoneal hypertonic glucose), and giving epineph-

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rine or sodium polyanethol sulfonate (Liquoid), to guinea pigs, Miles83 reduced markedly the minimal effective dose of bacteria required to produce a standard infection. This enhancement of infection ranged from two- to 100,000-fold. The body defenses inhibited by the enhancing agents were accordingly responsible for killing from 50 to 99.999 per cent of the bacteria originally constituting the primary lodgment. The period during which this effect could be obtained lasted only two to five hours after the injection of bacteria. After several hours the same challenge caused no effect on the development of the lesion. The enhancing agents inhibited either the access to the lesion or action in the lesion of bactericidal elements of the blood. * Since most wounds contain bacteria at the time of closure,57 the clinical parallel of a patient in postoperative shock is rather striking and is applicable in a relatively healthy as well as in a debilitated patient. Barnes et al.,12-16 in a series of papers which retroactively analyze infection rates over two decades at the Massachusetts General Hospital, have marshaled convincing clinical evidence in support of the "primary lodgment" concept and the importance of host factors. Their use of a standardized operation for long-term analysis, with increased sepsis risk patients excluded, provided an excellent tool with which to single out relevant determinants of infection. Data from 3336 inguinal herniorrhaphies and 6111 abdominal hysterectomies, with complicated cases excluded,t revealed no evidence of an increase or decrease in the risk of sepsis over a period of 21 years. Their data suggest strongly that recent high rates of surgical sepsis are most likely due to changes in the type of patient and in the extent of the surgery being carried out. They also demonstrated a marked decrease in the incidence of sepsis following subtotal gastrectomies in the period 1941 through 1953 (from 16 to 4 per cent) concurrent with the free availability of whole blood, and an increase beginning in 1954 (back to 9.4 per cent) concurrent with a change in the type of patient population tending toward a lower socioeconomic class requiring a greater number of emergency gastrectomies for bleeding. They have thus demonstrated the relative importance of host factors in their influence on sepsis rates. The Organisms

Finland et al. 40 showed a marked reduction in deaths due to certain pathogens, since the advent of antibacterial drugs, notably pneumococcus and hemolytic streptococcus. This was overshadowed, however, by the greater increase in cases and deaths from other infections and blood stream invasions with Staphylococcus aureus, enterococci, and the

* This corr~lated with susceptibility of the pathogen to the bactericidal action of the blood and serum in vitro. ' , tExcluded' were cases with cancer of the cervix, previous radiation, concurrent bladder or bowel surgery, inflammatory disease, etc.

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coliforms, including Aerobacter, Proteus and Pseudomonas which had not been previously considered highly pathogenic and which had rarely caused fatal infections before the era of antibacterial drugs. The most common pathogens found in wound infections in our experience in order of frequency are Staphylococcus aureus, enterococci, Pseudomonas pyocyaneus, Escherichia coli, Proteus species and Klebsiella aero genes. Whereas Staph. aureus has been the predominant offender in most hospitals, and still is on our service, many institutions are finding that gram-negative organisms are the main problem. 4G Pseudomonas, and to a lesser extent Proteus infections, are currently the main cause of death following burns. 6, 68, 79, 98 These organisms are particularly difficult to treat with specific antibiotics. They are common components of the flora in wound sepsis, and Pseudomonas infections are particularly liable to cause a terminal septicemia in debilitated patients with an extremely high mortality.6 A succinct review of the pertinent characteristics of the principal micro-organisms of surgical importance has been presented recently by Pulaski. 9 & The Environment

Articles describing the degree of contamination of various aspects of the hospital environment (air, floors, bedding, carafes, etc.) and advocating multifactor approaches for control and prevention of infection are too numerous to list here and have recently been collected and summarized by Nahmias and Eickhoff. 84 Most of the evidence incriminating the environment is circumstantial. There are many quantitative studies before and after various antiseptic techniques designed to lower the environmental bacterial population but few studies relating quantitative findings to the incidence of infection. The criterion for success should be a lowering in sepsis rates, not in bacterial counts. There is little information· on levels of contamination considered hazardous to patients or personnel. Burke and Corrigan22 in a study of the epidemiology of a surgical ward found that the only staphylococcal source causing heavy and persistent contamination of the environment was the open infection. This appeared to be a prime source of cross infection. Astudy reported from this laboratory59 failed to incriminate mattresses as important reservoirs of staphylococci. Eighty per cent of the blankets became lightly contaminated with Staph. aureus after eight weeks of use but the seven postoperative wound infections occurring during the study were caused by strains of a different bacteriophage pattern than the one carried on the blanket. In another study,57 the specific personnel and environment concerned with the operative and ward management of 330 selected patients undergoing major operations were bacteriologically monitored for staphylo-

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cocci. Over 13,500 cultures were taken. Postoperative wound infections due to Staph. aureus developed in 18 patients. In about half of them it was possible to show by bacteriophage typing a definite (six cases) or questionable (four cases) relationship to some source of infection. In all ten instances the data pointed toward people, either personnel or the patients themselves, as the source of contamination, and indicated that the majority of serious infections that could be documented in clean closed wounds were seeded in the operating room during surgery. Secondary staphylococcal contamination by ward carriers of open, draining wounds already infected with other bacteria probably seeded during surgery was demonstrated. Such ward contamination is not believed to be a frequent source of serious primary infection in closed wounds. In no instance could we incriminate the floor, air, bed linen, mattress, mattress cover, bedside curtain or surgeon's gloves as a primary source of infection in a clean closed wound. In one instance a patient's blanket was indicated as a source of secondary contamination in a wound already infected and draining. It would appear that, if the inanimate environment had been an important direct source of infection under the nonepidemic conditions studied, it would have been possible to document the fact more frequently in comparison to the number of people who were documented as sources. Staphylococcus aureus was cultured from the air during 22 operations. 68 Five of these patients developed wound sepsis but in each case with a strain of a different phage type than was cultured from the air. The degree of atmospheric contamination under which these results were obtained is indicated by a mean colony count of approximately 4.5 per cubic foot of air and a mean settling rate of approximately 187 colonies per square foot per hour with wide variations. Staphylococcus aureus was cultured during 12 operations and averaged 0.79 colonies per cubic foot with a mean settling rate of 39 colonies per square foot per hour. Rittenburg et al. 99 reported on an elaborately constructed "pathogenfree care area" for susceptible patients. They showed 77 per cent of cultured surfaces to be sterile and reduced the air count to 19 bacteria per mm. 3 but no data on sepsis were presented. Our own regimen aimed at prevention of cross infection, when viewed in retrospect, must be considered as without demonstrable effect. An initial drop in infection rate during 1954 and 1955 gave encouragement at the time of publication62 (Fig. 1) but in 1956 the rate equaled its previous levels while the preventive program was in use. The environment, of course, can be at fault and has been shown to be the source of epidemics. Obviously, there are levels of bacterial contamination that are hazardous based on health rationale and levels for which it is practical and reasonable to strive. They have, to our knowledge,

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never been acceptably and reasonably defined. Our studies were carried out under nonepidemic conditions. The substrate was an environment where efforts toward good housekeeping were being made. 57 • 59 Cleanliness and good aseptic techniques were considered requisites. Infection Rates

Recording meaningful wound sepsis rates is a difficult task. No universally applicable simple and suitable method has yet been devised and the results vary according to the character of the hospital, patients and criteria used. Comparisons between institutions, therefore, are not valid. On general services the selection and analysis of a standard operation is a useful monitoring device to detect trends and relevant causal factors, but since standardization requires exclusion of the very infection-prone patients who are most likely to become septic, it does not reflect the actual overall number of infections being encountered. It is this total final result including the newer, extensive surgery on all types of patients that we must record, face up to, and improve upon, regardless of genesis, for infected patients and personnel appears to be the prime sources of cross contamination. 22 Complete reporting by types of operation becomes quite complex because of the ancillary procedures so frequently accompanying the standard operation, yet to exclude complicated cases hides the overall true picture. An anatomic regional approach was employed recently by Ketchum et aUo with some success. Until we can devise a better scheme on our service, where anatomic classification is relatively meaningless on a yearly basis because of small volume, we have continued to use a system for weekly reporting, previously published,51 which classifies wounds as clean (A), clean contaminated (B), or dirty (C) and establishes criteria for major and minor sepsis. Realizing its shortcomings, we feel that its main virtue is that it reflects the total picture of the sepsis with which we must deal. Periodic retrospective analysis of the "standard operation" type is desirable if the personnel and financial aid are available. As we observe the development of our own infection rate curves since 1949 (Fig. 1) and those of others (Fig. 2), it is obvious that there is almost a cadence in the marked fluctuations from year to year. If a prophylactic program is started at a peak in the curve it can be destined for nothing but statistical success regardless of its merit. Furthermore, one can demonstrate statistical significance in a rising or falling segment of the normally fluctuating curve if the size of the sample is large enough. This, of course, may lead to false conclusions. It would appear that, to have convincing evidence for a preventive program, it would be necessary first to establish the normal variations over a period of several years-and that the rate should be lowered and held to a degree significantly greater than the variation. Finland et al.,40 using standardized entities, have shown that the initial impact of antibacterial agents lowered the number of deaths from

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MAJOR WOUND INFECTION RATE - CLEAN OPERATIONS 1167 Operations per Year (av.)

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MAJOR SEPSIS - 3336 INGUINAL HERNIORRHAPHIES ( MASS. GENERAL HOSPITAL)

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Fig. 2. Adapted from Barnes et al., Surgery 46: 247, 1959 (Fig. 3).

infections at the Boston City Hospital through 1947 but there followed a significant and steady increase beyond that which antedated the era of the antibacterial drugs. The increase was associated with the reduced effectiveness of drugs against staphylococcal infections and, following the suppression of antibiotic-sensitive pneumococci and streptococci, with an increase in incidence of enterococcal and gram-negative infections against which available drugs had only slight activity, Examination of our own infection rates in retrospect and with these considerations in mind (Fig. 1) shows no meaningful trends in either direction, at least since 1953. The rise from 1949 to 1953 was in the period

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when antibiotic usage and the development of resistance was at its peak and, because of its span and lack of fluctuation, may represent a return to former rates after the initial favorable impact of antibiotics which occurred before 1949. This would be in keeping with the findings of Finland et al. 40 and Altemeier. 43 What then has been achieved as regards infection rates? We are aware of reports ranging from 0.29 19 to 55.6 70 per cent. Two of the best studies are those of Barnes et al./5 who report "standardized operation" rates ranging from 1.7 to 9.4 per cent for various procedures. and of the Public Health Laboratory Service of England and Wales, 95 which reports an overall sepsis rate of 9.7 per cent. Both of these studies probably underestimate the full problem because, for reasons of experimental design, certain types of cases particularly prone to sepsis were omitted from the series. Sepsis, however, is not confined to the more complex operations 95 and the actual rates are probably much higher than most surgeons are aware of. In summary, it would appear that two factors have contributed strongly to the present day problem of surgical sepsis. These factors are (1) an increasing amount of extensive surgery on a greater number of infection-prone patients and (2) changes in the numbers and types of bacterial infections as a consequence of the use of antibiotics (emergence to predominance of resistant, pathogenic organisms).*, 40 The foregoing considerations suggest that, although analysis of standardized operation infection rates indicates no increased sepsis risk per se, the total amount of postoperative sepsis with which we must deal in proportion to the number of operations performed is greater than before these factors came into play. The accumulation of more septic cases in hospitals may affect adversely the sepsis risk via cross contamination between patients and personnel. Staphylococcal Nasal and Skin Carriers

Without making an attempt to cover the extensive literature on carriers,t a few points relevant to postoperative infections will be discussed. Although the evidence is often indirect, the asymptomatic carrier may be important as a source of wound sepsis. ll5 The documentation of people as sources of infection and the fact that the air could not be incriminated, in a recent study by Howe and Marston,57 supports the importance of carriers and of direct contact transmission of infection. Although there are some dissenting opinions,95 the bulk of evidence indicates that patients who are nasal carriers of Staph. aureus experience a significantly higher wound infection rate than noncarriers.70, 116

* The overall impact of antibiotics, however, has been good when such diseases as osteomyelitis, mastoiditis, syphilis, pneumococcal, beta hemolytic streptococcal infections, etc. are considered. t See Nahmias and Eickhoff. 84

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How to deal with hospital personnel who are carriers of staphylococci of the 80/81 complex or other epidemic strains is a vexing question to many. Our studies indicated no logical bases for exclusion of carriers from hospital duty. Strains causing wound sepsis were unpredictably varied and did not correlate quantitatively with 80/81, endemic, or other predominant strains among personnel. In retrospect, it is apparent that excluding personnel from duty because of carriage of a particular strain would have created a very seriom: personnel shortage and would have accomplished nothing. In our opinion, screening by culturing and bacteriophage typing is indicated only when outbreaks or clusters of staphylococcal sepsis occur. Carriers incriminated in this fashion by proper epidemiological methods, when there is actual trouble at hand, should be relieved from duty. The treatment of asymptomatic carriers has been rather unsuccessful except for one particular type, namely those who experience recurrent staphylococcal lesions themselves. Here the use of antibacterial nasal creams apparently decreases the number of recurrent lesions. 28 . 47 Needless to say, personnel with open draining staphylococcal lesions, such as furuncles, should go immediately off duty until healed and such patients should be managed under appropriate precautions. For the mo~t part, nasal creams reduce the carrier rate among personnel and patients but cannot be demonstrated to have an effect on the rate of hospital sepsis. 48 . 75 In adult carriers, systemic antibiotics are suppressive for a few days but the same resistant flora usually recurs. 72 The newer penicillinaseresistant penicillins cannot be depended upon to eliminate nasal staphylococci,!· 101. lIO Whether or not nasal colonization in a surgical ward is a measure of staphylococcal contamination of the environment and only an indirect cause of wound sepsis is an unanswered question. Before leaving the subject of carriers, mention should be made of the "cloud baby" phenomenon, an example of bacterial-viral interaction reported by Eichenwald et aJ.37 whereby certain infants in nurseries were shown to disseminate staphylococci to a greater degree than others. The factor responsible for the dissemination appears to consist of a number of respiratory viruses occasionally encountered in hospitalized newborn infants. This may be an important concept applicable to operating room carriers and postoperative infections. As with adult carriers, only a small minority of babies are highly infectious to others and these, i.e., the "cloud babies," may not present overt signs of disease. It is suggested that a search be made for "cloud adult" carriers in operating rooms as dangerous spreaders of staphylococci because of the presence of viruses. Diagnostic and Pathogenic Features of Wound Infection

Postoperative wound infections are generally manifested by the fourth or fifth day. Usually there is a fever. Edema may be the first sign of a deep infection. but the most important early sign is undue pain. The

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surface appearance of the lesion is often deceiving, the extent of the septic process being much greater in the depths of the wound than denoted by its external appearance. Facial slough begins on about the third or fourth day-especially if the organism elaborates a necrotizing toxin. In many types of infection a marked thrombosis of surrounding blood vessels is an important part of the picture. Wound dehiscence is not usually caused by infection per se unless neglected and advanced. Some organisms may remain alive inside phagocytes. 61 , 112 When in this state they are protected from antibiotics. Phagocytes may migrate and later explode releasing viable organisms into new tissues. 61 Wound infection as commonly seen is a suppurative process and i8 essentially an abscess. It is the septic breakdown of necrotic tissues and blood clot. Staphylococcal infections tend to localize, lay down fibrin and form abscesses. There may be surrounding cellulitis. Pseudomonas wound infections frequently develop as a superinfection. Pseudomonas septicemia in burn patients most often follows the staphylococcal bacteremia. 98 Clinical features of septicemia are hypothermia, leukopenic white cell count, and circumscribed areas of hemorrhagic skin necrosis which upon microscopic examination are characterized by vast numbers of organisms in the walls of small arteries. Frequently, widespread black necrosis develops in burn wounds infected with this organism. Vesicular or nodular areas may develop in the skin. Treatment

PROPHYLAXIS. The most effective prophylactic measure against wound sepsis lies in excellence of surgical technique. In human volunteers, Elek and Conen39 showed that the presence of suture material enhanced the infective power of Staph. aureus 1000 to 10,000 times. Wounds closed with fine sutures, accurate hemostasis, without tension or dead space and with a minimum number of crushed cells seldom become infected. There are several studies demonstrating that routine prophylactic antibiotics do not prevent sepsis and may increase the chance of wound and pulmonary infection rather than decrease it.74, 80, 90, 91 Most authors5, 96 recommend systemic prophylactic antibiotic therapy in certain special procedures involving contaminated fields but not in "clean" cases. Ketchum et al.,70 in a double blind study, reported a remarkable infection rate of 55.6 per cent using placebo therapy and 14 per cent using chloramphenicol on patients having extensive cancer operations. More such controlled studies are needed in those specialized areas where benefits are claimed for prophylaxis without convincing evidence. To use it with all operations which transgress an area or tract normally harboring bacteria will result in routine prophylaxis for the majority of abdominal and pulmonary operations. We have avoided

1 !i

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systemic prophylaxis in clean (A) or clean contaminated (B) cases where normal healing should be expected with proper surgical technique. 53 Clinical data such as those already mentioned from the study by Ketchum,7° experimental evidence such as presented by Burke,21 and new developments in the antibiotic field should reopen the question of systemic antibiotic prophylaxis for further exploration. Using experimental techniques in animals similar to those devised by Miles, Burke21 demonstrated a· definite short period, over in three hours after inoculation, when developing infections caused by sensitive staphylococci may be suppressed by systemic antibiotics. These agents caused maximal suppression if given before bacteria arrived in the tissue. The question is raised, therefore, as to whether or not antibiotics have been given early enough in some previous studies on prophylaxis. This, together with the development of new penicillins which are not inhibited by staphylococcal penicillinase, suggests that new controlled studies be carried out. It is to be hoped, however, that these new drugs will not be used routinely and indiscriminately for prophylaxis until proof of their value and adequate data as to development of resistance of bacteria to them are at hand. The hope that antibiotics eventually will be found universally and significantly to reduce wound sepsis is a dim one. The problem is complex and involves host resistance, foreign bodies (sutures), surgical skill (hematomas, tension, trauma) and in most cases a polybacterial flora in situations where resistant strains are present or almost sure to appear. This latter factor is the bugbear of surgical prophylaxis. The successes have been in medical monobacterial infections with single drugs that are effective in low concentrations. 63 When prophylactic therapy is directed against mixed gram-positive and gram-negative organisms, it is almost inevitable that a resistant strain eventually will emerge to predominance. In this case, therapy does nothing to the resistance of the host and does not change the critical balance between numerous other factors operating as determinants. It may, however, set the stage so that if an infection is to occur the causal organism will be an antibiotic-resistant strain. Using topical agents, Howes 61 in 1946 demonstrated the same phenomenon regarding the three-hour interval of antibiotic effectiveness shown by Burke21 with systemic antibiotics. The rationale for topical prophylactic antibacterial therapy to keep contaminated wounds from becoming septic is based on the fact that drugs can be applied directly at the site of infection at the time of contamination in nontoxic concentrations much higher than obtainable parenterally and above those required to kill most common wound pathogens. Rabbits with crushed contaminated wounds were protected from infection if the solution (streptomycin-sulfamylon) was injected within three hours.* Pulaski

* Howes, in discussing Burke's work,21 called attention to the fact that the idea originated with Friedrich, professor of Surgery at Leipzig, who demonstrated that few wounds debrided before 6 hours became infected, but after that time the rate progressively increased until after 12 hours when all became septic despite debridement. '2

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et alY and others have demonstrated the clinical effectiveness of local antibiotics in the wound at the time of contamination. There is evidence that antibiotics and chemotherapeutic agents applied locally will penetrate abraded or diseased skin, fat and fascia quite readily.60 Here again the situation is complex and influenced by host resistance and the presence of necrotic tissue but appears worthy of further trial in severely contaminated cases. ESTABLISHED INFECTIONS. The fundamental principles of wound sepsis management remain unchanged by the advent of antibiotics. The following points are relevant. Wound infections caused by more than one type of bacteria (polybacterial infections) are likely to be more vicious and destructive because of the symbiotic action between organisms. Products of one strain may protect another from antibiotic action and make the infection more difficult to, treat. For this reason, infected wounds should be handled with the same aseptic techniques as used in the operating room on fresh tissues to avoid introducing new organisms during examination or treatment. Properly chosen antibiotics administered early will control invasive unlocalized infection. Such therapy will also control the cellulitis component around an infected wound. Once the process has localized, however, and there is pus and necrotic tissue present, antibiotics will not cure the infection even though the organism is sensitive to the antibiotic given. This is the stage in which most wound infections are diagnosed and they require incision and drainage. The function of antibiotics in early invasive infection (cellulitis) is a curative one but the function of antibiotics in the treatment of a wound abscess is adjunctive. These drugs help prevent peripheral complications and septicemia, and their use is incident to adequate surgical drainage of the lesion. They will not cure wound suppuration. Once the diagnosis of deep-seated localized wound suppuration is made, immediate drainage should be carried out under appropriate systemic antibiotic covElrage before extensive sloughing of fascia occurs. The adjunctive use of systemic antibiotics allows a more aggressive surgical attack on the lesion than formerly. This may include complete debridement at the time of drainage, thereby immediately converting a septic wound into a clean contaminated one which may be closed secondarily in two to four days. 55 In serious infections, because of the usual wide extent of the septic process in the deep part of the wound, the latter should be opened for its full length at the time of drainage. All suture material should be removed. It will heal quicker if this is done. Common Mistakes in Management. Some of the more common mistakes observed in the management of infected wounds are as follows:

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1. Persistent, prolonged treatment with antibiotics with the hope of cure when the wound needs incision and drainage. 2. Carrying out drainage with the patient in bed on the ward without proper skin preparation and draping and without the use of aseptic techniques so that the wound is contaminated with additional organisms. 3. The use of excessively large packs in an infected wound that has been opened. These packs often serve to block the escape of exudates and tend to cause gaping so that the wound becomes fixed in an open position making secondary healing or closure more difficult. Drains, or one or two layers of fine mesh gauze, are usually sufficient. 4. Inadequate dressings. Organisms penetrate dlessings with ease in either direction, especially when the dressing is wet. Dressings for wound sepsis should be sealed all the way around the edges and thick enough to prevent penetration of any moisture. When there is excessive discharge, inclusion of plastic or rubber sheeting in the dressing helps make it occlusive and prevents recontamination of the wound itself as well as the personnel and the environment. PULMONARY COMPLICATIONS

The incidence of pulmonary complications shown in Table 1 would doubtless have been higher, as it is in other series, had stringent standardized criteria and routine roentgenography been employed. It is also probable that many of pneumonias were actually atelectasis or preceded by it. The underlying feature common to all postoperative pulmonary complications is an interference with pulmonary function and is most marked after upper abdominal operations. 7 It is in the patient with chronic respiratory impairment that infection is most likely to follow. More attention, therefore, has been focused recently on the preoperative estimation of pulmonary function. Mild bronchitis or emphysema of sufficient severity to influence profoundly the postoperative course of patients undergoing extensive surgical procedures may be easily overlooked upon clinical evaluation of pulmonary function by history, physical examination and x-rays. Stein et al.,l°9 using a battery of several tests on randomly selected patients without histories of lung disease, found one pulmonary complication in 33 patients who were considered normal by these studies versus 21 complication!'! in 30 patients considered abnormal. Decreased expiratory flow rates had the best correlation and elevated alveolar carbon dioxide tension (pC0 2) was of great significance. General surgeons are beginning to appreciate and utilize pulmonary function tests formerly understood only by the thoracic surgeon. The increasing importance of chronic bronchitis and its complications, its relationship to infections and its treatment have been summarized

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recently by Keefer, 67 and its importance to surgeons as :regards postoperative pulmonary complications has been emphasized. 43 . 109 This disease is defined as chronic or recurrent excessive mucous secretion clinically manifested by cough and expectoration, not attributable to other pulmonary conditions. Infection of the bronchi is frequently but not necessarily present. Subjects may produce sputum and deny cough. Some may habitually swallow sputum. 24 It is clear that smoking has a deleterious influence on pulmonary function and hence predisposes to postoperative infection. In a recent review, Gaensler43 found 14 epidemiologic studies on smoking covering a wide range of occupations. Every report he encountered showed both a higher prevalance of respiratory symptoms and lower mean ventilatory capacity in smokers than in nonsmokers. Heavy smokers were more seriously affected than light smokers and those who smoked down to short butts were most affected. The incidence of heavy smokers among patients with chronic bronchitis and obstructive emphysema was unusually high in most series reviewed. McIlroy and N adel 78 found airway conductance reduced to one-half control values in most normal smokers and nonsmokers. The effect could be produced by a single inhalation, lasted as long as an hour and could be reversed by inhalation of isoproterenol aerosol. Respiratory acidosis (hypercarbia) may develop several days after an operation as a result of progressive atelectasis or bronchopneumonia often combined with interstitial pulmonary edema from excess fluid therapy.44 It is frequently unrecognized until cyanosis or CO 2 narcosis has occurred. Neurological symptoms may suggest brain tumor,9. 107 or it may be mistaken for the after-effects of anesthesia. It should be suspected with an unexplained fall in blood pressure. Early diagnosis is facilitated by laboratory tests recently discussed by Gaensler,43 who summarizes the eight most commonly used and practical methods. The rebreathing technique (20 seconds) is probably the simplest and is suitable for postoperative use. It requires an anesthesia bag and an infra-red analyzer or a modified Haldane apparatus. It gives a mixed venous pC02 reading which iA satisfactorily converted to arterial CO 2 tension by simply subtracting 6 mm. Hg from the result. Mention should be made of aspiration pneumonitis as a pulmonary complication. It may produce severe chemical inflammation and sepsis resulting in a moribund patient in a few hours. One may be deceived by a relatively negative physical examination of the chest in contrast to the extensive pathology revealed by x-ray. Treatment PROPHYLAXIS. The most effective treatment for postoperative pulmonary infection is its prevention by attention to measures designed to enhance pulmonary function. Every effort should be made to recognize

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preoperatively patients with obvious or obscure impairment. They should refrain from smoking for a week preoperatively and a routine of increased activity, postural drainage, deep breathing exercises, coughing, inhalation of bronchodilator aerosols and clapping percussion of the chest wall should be instituted. 87 Routine antibiotic prophylaxis directed against postoperative pulmonary complications can alter the bacterial flora, cause resistant strains to emerge to predominance, but does nothing to prevent infection. It may set the stage so that if infection does develop it will be with an antibiotic-resistant organism. Mark Lepper et al. 74 showed what actually happens to the flora in the trachea when prophylaxis is given. No drug or combination improved the situation. The number of organisms in tracheotomized patients actually increased over normal except when t.hree or more antibiotics were given together. Petersdorf et al. 90 studied prophylaxis in comatose patients. In 45 per cent of the treated group, pneumonitis developed whereas it occurred in only 15 per cent of controls. Penicillin and breathing exercises did not reduce postoperative pulmonary complications in 160 inguinal herniorrhaphy patients studied by Palmer and Sellick. 86 ..: ' These remarks do not apply to preoperative antibiotic therapy in bronchiectasis or other diseases involving stasis, obstruction or infection. Such therapy has been proved beneficial. It is, in reality, the treatment of chronic infection and does not come under the category of prophylaxis. There is evidence that intermittent positive pressure breathing will not prevent atelectasis 01' accelerate its c.learance in patients with a normal bronchial tree. I8 Many articles attesting to its virtue are of the testimonial type. It is often advocated preoperatively and postoperatively for patients with chronic bronchial disease. A recent physiologic study by Kamat et a1. 63 indicated that it was either nonbeneficial or actually harmful in this type of case. Many of the beneficial effects can be attributed to the bronchodilator aerosols used with the artificial ventilation. These alone, if properly administered, have been shown to be as effective as when combined with intermittent positive pressure breathing. 43 ESTABLISHED INFECTION. The treatment of postoperative pneumonia consists of specific antibiotic therapy based on sputum cultures, together with the usual ancillary measures. The treatment of established atelectasis consists of the same measures outlined under "Prophylaxis." When these do not suffice, tracheal aspiration or even bronchoscopic aspiration (for extensive involvement or massive collapse) should be added. Antibiotics, the avoidance of atropinelike drugs and the use of minimal amounts of intravenous fluids, whenever possible, are adjunctive measures. Carbon dioxide inhalations are not recommended and oxygen therapy should be used with care only in

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the face of air hunger or cyanosis. A lung filled with oxygen collapses more readily than one filled with air. The following suggestions regarding the treatment of postoperative re8piratory acido8i8 are necessarily brief and incomplete. Shock position. tracheal suction, bronchodilator therapy and humidification are well known. Tracheostomy is being and should be carried out earlier and with greater frequency in the prevention and management of respiratory acidosis and other pulmonary complications. It facilitates removal of secretions, and reduces the anatomic dead space by about half.44 It has the disadvantage of depriving the lower respiratory tract of the filtering action of the upper airways and makes it vulnerable to bacterial contamination during aspiration. When tracheal or nasal suction is in use, a package of sterile catheters should be left at the bedside and a new catheter should be used and discarded for each aspiration. 56 It is in the patient with postoperative respiratory acidosis that the use of intermittent positive pressure breathing would appear to have its greatest application. Its use is greatly facilitated by tracheostomy and a rubber tube with inflatable cuff. It may not be effective in diffuse obstructive disease where difficulty is largely expiratory, because only inspiration can be assisted and under certain circumstances it may be harmful. 44 After prolonged anesthesia and extensive surgery, artificial ventilation allows respiratory control of semicomatose patients and affords a convenient means of administering aerosols. For the treatment of a8piration pneumoniti8, prompt diagnosis and the early intravenous administration of hydrocortisone in 100 mg. doses t.i.d. for two or three days may be lifesaving. Aminophylline (500 mg. in 500 ml. of dextrose and water) may be used to prevent bronchospasm.11, 34 MISCELLANEOUS COMPLICATIONS

The complications listed under the miscellaneous heading in Table 1 are too numerous to discuss in full here. The following comments reflect important or current concepts relative to some of the more common ones. The overall clinical history and bacteriology of 8Ubdiaphragmatic ab8ce88 has changed little over the past several decades. Dineen and McSherry recently have reviewed their last 30 years' experience with this complication. 33 The results of treatment are disappointing; most series still report a mortality of 30 to 50 per cent. 33 , 114 Antibiotics may attenuate the abscess and delay diagnosis but definitive surgical drainage remains the only effective treatment. Chronic illness and obscure fever of several months' duration are common and delay undoubtedly is reflected in the high mortality rate. The advantage of the traditional extrapJeural approach over transperitoneal drainage has been challenged. 33

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Primary genitourinary infections in patients without obstructive uropathy caused by antibiotic-sensitive organisms can be bacteriologically controlled in 90 to 95 per cent of cases. 64 , 65, 66 Following reinfection, usually with mixed resistant organisms, the cure rate drops to 10 to 20 per cent. 64 Despite rigid aseptic precautions, catheterization or instrumentation predisposes to sepsis and should be avoided if at all possible. When drainage is necessary, intermittent catheterization is less likely to produce significant bacteriuria than an indwelling catheter, despite chemotherapy.l06 In our experience, early ambulation and the use of a bedside commode are singularly effective in promoting natural voiding by patients who fail with a bed pan. Bacterial colony counts are a practical method of distinguishing between contamination during collection (10,000 colonies per ml. or less) versus significant clinical infection (100,000 per ml. or more). 65 In the literature on bacterial peritonitis, it is difficult to find convincing evidence supporting a preference for any particular antibiotic regimen when cultures are not obtainable. Large doses of penicillin together with streptomycin are still used by most surgeons, while others prefer the broad-spectrum drugs.4, 17 More recently kanamycin has been used because of its broad-spectrum, antistaphylococcal and bactericidal qualities, either alone or with penicillin. One should be aware of its toxic potential and not exceed a total dose of 20 grams. The intraperitoneal instillation of tetracyclines causes pain, chemical peritonitis and adhesions. 25 , 105 Intraperitoneal neomycin has been shown to be very effective but may cause respiratory arrest by a neuromuscular blocking action during anesthesia with ether or when d-tubocurarine is used. Intraperitoneal kanamycin plus systemic antibiotics yielded excellent results in 75 patients treated by Cohn/5, 26, 29 but in two instances reported by Artz 8 apnea has been noted following its use in anesthetized patients given curare. It would appear prudent to introduce these drugs after recovery from anesthesia through fine plastic catheters placed at operation, and to have resuscitative facilities at hand. Prostigmine antagonizes the neuromuscular blocking effect of neomycin. Prohaska et al. 94 present evidence showing that pseudomembranous and staphylococcal enterocolitis are one and the same disease, that the pathological changes are caused by staphylococcal enterotoxin, and that it occurs most commonly following major intestinal surgery and the administration of antibiotics. It appears to occur more commonly in females (ratio of 4: 1). It may manifest itself with hyperactive bowel sounds and yet paradoxically there may be abdominal distention and an x-ray pattern suggesting ileus. 89 , 92, 93, 94 Mortality rates are in the range of 50 to 75 per cent89 and therapy consists in omitting current antibiotic therapy, restoration of fluid and electrolyte balance and, if necessary, substituting specific antistaphylococcal antibiotic therapy based on sensitivity tests. Prohaska et al. 92 reported that intramuscular ACTH,

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40 units three times daily for three to seven days in diminishing doses, may result in marked improvement. They postulate that ACTH has a nullifying effect on staphylococcal enterotoxin. Cortisone was not effective. Eiseman et al.3 8 and others have used fecal enemas to help restore the normal colonic flora. Antibiotic resistant strains of Staph. aureus are now the most common cause of postoperative parotitis, which is still a dangerous entity with a high mortality despite antibiotics. 20 . 46. 102. 108 Laryngotracheal obstruction may develop within a few hours and requires early surgical drainage before fluctuation appears. Bacterial endocarditis appears to occur more frequently following cardiac surgical procedures involving extracorporeal circulation or hypothermia than it does following other cardiac procedures. 32 . n A number of cases have been reported where reoperation and removal of silk sutures controlled the situation after intense antibiotic therapy had failed.10. 69 Septic shock is caused by endotoxins from gram-negative organisms in most instances. Treatment consists of specific intravenous antibiotic therapy, maintenance of fluid and electrolyte balance, and vasopressors. The role ·of exogenous steroids .is controversial. Tenney et al. 1l1 and others2. 31 report good results with early curettage under antibiotic protection for septic abortion. Gravely ill patients frequently tolerate surgical removal of septic tissue better. than continued severe infection.76. 77 ANTIBIOTICS

Among the many developments in this area, the following appear worthy of mention as regards the treatment of postoperative infections. A. New Penicillins. By adding side chains to the penicillin nucleus new . drugs with special qualities are available. lit' 1. Methicillin (Staphcillin, Dimocillin, Celbenin) has a spectrum similar to benzyl penicillin (penicillin G) but it is not inhibited by staphylococcal penicillinase. It is about one-fiftieth as effective against beta-hemolytic streptococcus. It is inactivated by procaine but may be mixed with Xylocaine. For very severe staphylococcal infections large doses are required (3 to 5 grams q. 6 h. for a week, then 8 to 12 grams a day for three to six weeks). It appears in the bile, pleural, synovial and cerebrospinal fluids. 2. Oxacillin (Prostaphlin, P12), also penicillinase-resistant, is five to eight times more active than methicillin. It is well absorbed orally and probably ~oon .will be available for parenteral use. Early reports with these drugs are favorable but superinfection with gramnegative organisms is proving to be a problem. 104 3.6-(2-Ethoxy-1-naphthamido) penicillanic acid (Nafcillin) is a new penicillin in the process of being studied and appears promising for surgical infections by virtue of its ability to diffuse into tissues. It is active against penicillinase

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producers and the parenteral form appears most useful. Very little clinical information is available as yet. 4. d-Aminobenzyl penicillin (Ampicillin, Penbritin, P50, BRL 1341) is a readily absorbed broad-spectrum penicillin effective against all the major coccal pathogens as well as many strains of Escherichia coli, Proteus vulgaris, Shigella and Salmonella. It is not effective against Pseudomonas or Klebsiella aerobacter and is hydrolyzed by penicillinases elaborated by staphylococci and certain gram-negative organisms. B. Following the controversy as to the effectiveness of blood level enhancement of tetracyclines with glucosamine hydrochloride, phosphate complexes or citric acid,36 modified broad-spectrum formulas have been devised by adding (pyrrolidinomethyl tetracycline) or removing (demethylchlortetracycline) side chains to produce higher serum levels with lower dosage. In general, these attempts have been successful but the results are still the subject of controversy73. 100 and there is some question as to whether or not any of these compounds are more useful clinically than the original drugs except in special instances. Kanamycin 3-phenylsalicylate103 yields high levels of kanamycin base in the urine without appreciable serum levels and gives promise of becoming useful for urinary infections by virtue of reduced oto- and nephrotoxicity hazards. Many other new antibiotics are in the trial stage. C. The surgeon should be aware of the pitfalls of antibiotic sensitivity testing/ o the marked discrepancies between results using different brands of testing discs (lack of standardization),49 the relativity of sensitivity reports60 and the controversy which exists regarding the clinical value of disc testing. 88 D. Finally, there are three simple, yet important principles which need emphasis because they are frequently overlooked in hospitalized patients with serious infections. These are (a) that pretreatment cultures should always be taken when available, (b) that the higher tissue levels usually needed in surgical infections are more effectively obtained with regular benzyl penicillin than V\;ith procaine penicillin or other repository forms, and (c) that the intravenous administration of antibiotics (rather than intramuscular) to patients in shock or impending circulatory failure is necessary to insure adequate absorption. REFERENCES 1. Abramovitch, H. and Wolinsky, E.: Influence of three penicillins and cephalo-

2. 3. 4. 5. 6. 7.

sporin on eradication of staphylococci in nasal carriers. In abstracts of papers presented at the Second Interscience Conference on Antimicrobial Agents and Chemotherapy, Oct. 31-Nov. 2, 1962, to be published in Antimicrobial Agents and Chemotherapy, 1962. Adcock, L. L. and Hakanson, E. Y.: Vascular collapse complicating septic abortion. Am. J. Obst. & Gynec. 79: 516, 1960. Altemeier, W. A.: In discussion of Howe, C. W.: The problem of postoperative wound infections caused by Staphylococcus aureus. AmI. Surg. 146: 384, 1957. - - - and Culbertson, W. R.: Complications of appendectomy. In Complications in Surgery (G. P. Artz and J. D. Hardy, Eds.). Philadelphia, W. B. Saunders Co., 1960, p. 750. - - - , Culbertson, W. R. and Vetto, M.: Prophylactic antibiotic therapy (Editorial). Arch. Surg. 71: 2, 1955. - - - , MacMillan, B. G. and Hill, E. 0.: Rationale of specific antibiotic therapy in the management of major burns. Surgery 62: 240, 1962. Anscombe, A. R.: Pulmonary Complications in Abdominal Surgery. Chicago, Year Book Publishers, 1957, p. 118.

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8. Artz, C. P., Barnett, W. O. and Grogan, J. B.: Further studies concerning the pathogenesis and treatment of peritonitis. Ann. Surg. 155: 756, 1962. 9. Austen, F. K., Carmichael, M. W. and Adams, R. D.: Neurologic manifestations of chronic pulmonary insufficiency. New England J. Med. 257: 579, 1957. 10. Bahnson, H. T., Spencer, F. C. and Bennett, I. L., Jr.: Staphylococcal infections of the heart and great vessels due to silk sutures. Ann. Surg. 146: 399, 1957. 11. Bannister, W. K., SatiJIaro, A. J. and Otis, R. D.: Therapeutic aspects of aspiration pneumonitis. Anesthesiology 22: 440, 1961. 12. Barnes, B. A., Behringer, G. E., Wheelock, F. C. and Wilkins, E. W.: Surgical sepsis: Impressions and facts. Surgery 46: 247, 1959. 13. Idem: An analysis of factors associated with sepsis in two operative procedures. New England J. Med. 261: 1351,1959. 14. Idem: Surgical sepsis: Analysis of factors associated with sepsis following appendectomy (1937-1959). Ann. Surg. 156: 703, 1962. 15. Idem: Postoperative sepsis: Trends and factors influencing sepsis over a 20year period reviewed in 20,000 cases. Ann. Surg. 154: 585, 1961. 16. Barnes, B. A., Behringer, J. E., Wheelock, F. C., Wilkins, E. W. and Cope, 0.: Surgical sepsis: A report on subtotal gastrectomies. J.A.M.A. 173: 1068, 1960. 17. Barnett, W. O. and Hardy, J. D.: Shock in peritonitis-mechanisms and management. S. CLIN. NORTH AMERICA 42: 1101, 1962. 18. Becker, A., Barak, S., Braun, E. and Meyers, M. P.: Treatment of postoperative pulmonary atelectasis with intermittent positive pressure breathing. Surg. Gynec. & Obst. 111: 517,1960. 19. Brown, I. W.: In discussion of Barnes, B. A., Behringer, G. E., Wheelock, F. C. and Wilkins, E. W.: Postoperative sepsis: trends and factors influencing sepsis over a 20-year period reviewed in 20,000 cases. Ann. Surg. 154: 585, 1961. 20. Brown, J. V., Sedwitz, J. L. and Hanner, J. M.: Postoperative parotitis. A reappearing disease. U. S. Armed Forces M. J. 9: 161, 1958. 21. Burke, J. F.: The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 50: 161, 1961. 22. - - - and Corrigan, E. A.: Staphylococcal epidemiology on a surgical ward. New England J. Med. 264: 321, 1961. 23. Christie, R.: Chronic bronchitis and emphysema. Tr. and Studies of the Coli. of Physicians of Philadelphia 27: 12, 1959. 24. Ciba Guest Symposium: Terminology, definitions and classification of chronic pulmonary emphysema and related conditions. A report of the conclusions. Thorax 14: 286, 1959. 25. Cohn, 1., Jr.: Intraperitoneal antibiotic administration. Internat. Abstr. Surg. 114: 309, 1962. ~6. - - - and Cotlar, A.: Intraperitoneal kanamycin. Ann. Surg. 155: 532, 1962. 27. Colbeck, J. C.: Environmental aspects of staphylococcal infections acquired in hospitals. I. Hospital environment: its place in hospital staphylococcus infection problem. Am. J. Pub. Health 50: 468, 1960. 28. Copeman, P. W. M.: Treatment of recurrent styes. Lancet 2: 728, 1958. 29. Cotlar, A. M., Massari, F. S. and Cohn, I., Jr.: Intraperitoneal kanamycin in the treatment of peritonitis. In Antimicrobial Agents Annual, 1960, pp. 386-391, New York, Plenum Press, 1961. 30. Datta, N., Mossey, D. G., Doole, G. W. and Schneeweiss, J.: A trial with continuous winter chemotherapy in chronic bronchitis. Lancet 2: 723, 1960. 31. Deane, R. M. and Russell, K. P.: EnterobaciJIary septicemia and bacterial shock in septic abortion. Am. J. Obst. & Gynec. 79: 528, 1960. 32. Denton, C., Pappas, E. G., Uricchio, J. F., Goldberg, H. and Likoff, W.: Bacterial endocarditis following cardiac surgery. Circulation 15: 525, 1957. 33. Dineen, P. and McSherry, C. K.: Subdiaphragmatic abscess. Ann. Surg. 155' 506,1962. 34. Dines, D., Baker, W. G. and Scantland, W. A.: Aspiration pneumonitisMendelson's syndrome. J.A.M.A. 176: 229, 1961.

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35. Dubos, R.: The unknowns of staphylococcal infection. Ann. New York Acad. Sc. 65: 243, 1956. 36. Editorial. Enhanced absorption of tetracyclines. New England J. Med. 258: 97,1958. 37. Eichenwald, H. F., Kotsevalov, O. and Fasso, L. A.: The "Cloud Baby," an example of bacterial viral interaction. A.M.A. J. Dis. Child. 100: 161, 1960. 38. Eiseman, B., Silen, W., Bascomb, W. S. and Kauvor, A. J.: Fecal enema as an adjunct in the treatment of pseudomembranous entero colitis. Surgery 44: 854,1958. 39. Elek, S. D. and Conen, P. E.: The virulence of Staphylococcus pyogenes for man. A study of the problems of wound infections. Brit. J. Exper. Path. 38: 573, 1957. 40. Finland, M., Jones, W. F., Jr. and Barnes, M. W.: Changes in the occurence of serious bacterial infections since the introduction of antibacterial agents. Tr. A. Am. Physicians 72: 305, 1959. 41. Fletcher, C. M.: Disability and mortality from chronic bronchitis in relation to dust exposure. A.M.A. Arch. Industrial Health 18: 368, 1958. 42. Friedrich, P. L.: Die aseptische Versorgung frischer Wunden. Arch. f. kiin. Chir. 57: 288, 1898. 43. Gaensler, E. A.: Evaluation of pulmonary function: Results in chronic obstructive lung disease. Annual Rev. Med. 13: 319, 1962. 44. - - - : Respiratory acidosis following surgery. Am. J. Surg. 103: 289, 1962. 45. - - - and Lindgren, I.: Chronic bronchitis as an etiologic factor in obstructive emphysema. Am. Rev. Resp. Dis. 80: 185, 1959. 46. Gilchrist, R. K. and McAndrew, J. R.: Surgical parotitis. A.M.A. Arch. Surg. 76: 863, 1958. 47. Gould, J. C. and Cruickshank, J. D.: Staphylococcal infection in general practice. Lancet 2: 1157, 1957. 48. Henderson, R. J. and Williams, R. E. 0.: Nasal disinfection in prevention of postoperative staphylococcal infection of wounds. Brit. M. J. 2: 330, 1961. 49. Hill, E. 0., Altemeier, W. A. and Culbertson, W. R.: An appraisal of testing bacterial sensitivity to antibiotics. Ann. Surg. 148: 410, 1958. 50. Howe, C. W.: Treatment of staphylococcal infections. M. CLIN. NORTH AMERICA 37: 1461, 1953. 51. - - - : Postoperative wound infections due to Staphylococcus aureus. New England J. Med. 251: 411, 1954. 52. - - - : Prevention and control of postoperative wound infections owing to Staphylococcus aureus. New England J. Med. 255: 787,1956. 53. - - - : Prophylactic antibiotic therapy with special reference to gynecologic surgery. In Progress in Gynecology (J. V. Meigs and S. H. Sturgis, Eds.). New York, Grune & Stratton, Vol. 3, p. 735. 54. - - - : Staphylococcal disease on surgical services. Proc. National Conference on Hospital-Acquired Staphylococcal Disease, Atlanta, Ga., Sept. 15-17, 1958, p. 178. Washington, D.C., Government Printing Office, 1958. 55. - - - : Problem of the open wound in a hospital. Proc. Internat. Colloquium on Resistant Infections, Nov. 20-21, 1958, New York City, p. 114. Published by Eaton Laboratories, Norwich, New York, 1958. 56. - - - : In discussion of Head, J. M.: Tracheostomy in the management of respiratory problems. Tr. New England S. Soc. 41: 109, 1960. 57. - - - and Marston, A. T.: A study on sources of postoperative staphylococcal infection. Surg. Gynec. & Obst. 115: 266, 1962. 58. - - - and Marston, A. T.: Quantitative and qualitative bacteriological studies on hospital air as related to postoperative wound sepsis. J. Lab. & Clin. Med. (in press). 59. - - - , Silva, T. F. and Marston, A. T.: Staphylococcal contamination of mattresses and blankets on a surgical ward under nonepidernic conditions. New England J. Med. 264: 625, 1961. 60. - - - , Wigglesworth, W. C. and Kahn, R. E.: Distribution of antibiotics in blood and tissues with particular reference to penetration through skin, fat

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and fascia. In Surgical Forum, Clinical Congress of the Am. CoIl. of Surgeons, October, 1953. Philadelphia, W. B. Saunders Co., 1954, p. 621. 61. Howes, E. L.: Prevention of wound infection by the injection of nontoxic antibacterial substances. Ann. Surg. 124: 268, 1946. 62. - - - : In discussion of Burke, J. F.: The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 50: 161, 1961. 63. Kamat, S. R., Dulfano, M. J. and Segal, M.: Effects of intermittent positive pressure breathing (IPPB/I) with compressed air in patients with severe nonspecific obstructive pulmonary disease. Am. Rev. Resp. Dis. 86: 360, 1962. 64. Kass, E. H.: Chemotherapeutic and antibiotic drugs in the management of infections of the urinary tract. Am. J. Med. 18: 764, 1955. 65. - - - : Bacteriuria and the diagnosis of infections of the urinary tract. A.M.A. Arch. Int. Med. 100: 709, 1957. 66. - - - : Bacteriuria and the pathogenesis of pyelonephritis. Lab. Invest. 9: 110,1960. 67. Keefer, C. S.: The challenge of chronic bronchitis. Am. Pract. & Dig. of Treatment 2: 27a, 1960. 68. Kefalides, N. A., Arana, J. A., Bazan, A., Bocanegra, M., Statsny, P., Velarde, N. and Rosenthal, S. M.: Role of infection in mortality from severe burns. New England J. Med. 267: 318, 1962. 69. Kelsch, J. V. and Thomson, N. B., Jr.: Bacterial endocarditis complicating repair of ventricular septal defect. New England J. Med. 265: 1245, 1961. 70. Ketchum, A. S., Blade, J. H., Crawford, D. T., Leiberman, J. E. and Smith, R. R.: Role of prophylactic antibiotic therapy in control of staphylococcal infections following cancer surgery. Surg. Gynec. & Obst. 114: 345, 1962. 71. Kittle, C. F. and Reed, W. A.: Antibiotics and extracorporeal circulation. J. Thoracic & Cardiovasc. Surg. 41: 34,1961. 72. Knight, V., White, A., Hemmerley, T. and Martin, M. P.: Studies on origin of drug-resistant staphylococci in a mental hospital. Tr. Am. Clin. & Climatol. A. 70: 30, 1958. 73. Kunin, C. M. and Finland, M.: Demethylchloretetracycline. New England J. Med. 259: 999, 1958. 74. Lepper, M. H., Kofman, S., Blatt, N., Dowling, H. F. and Jackson, G. G.: Effect of eight antibiotics used singly and in combination on the tracheal flora following tracheotomy in poliomyelitis. Antibiotics & Chemotherapy 4: 829,1954. 75. Lepper, M. H., Dowling, H. F., Jackson, G. G., Spies, H. W. and Norsen, J.: Effect of antibiotic nasal ointments on carrier states in patients and on the antibiotic pattern of organisms from personnel caring for these patients. In abstracts of papers presented at the Second Interscience Conference on Antimicrobial Agents and Chemotherapy, Oct. 31-Nov. 2, 1962. To be published in Antimicrobial Agents and Chemotherapy, 1962. 76. MacLean, L. D., Weil, M. H., Spink, W. W. and Visscher, M. B.: On the canine intestinal and liver weight changes induced by Escherichia coli endotoxin. Proc. Soc. Exper. BioI., N.Y. 92: 602,1956. 77. MacLean, L. D.: Pathogenesis and treatment of bacteremic shock. Internat. Abstr. Surg. 115: 307, 1962. 78. McIlroy, M. B. and Nadel, J. A.: The air we breathe (Farber, S. M. and Wilson, R. H. L., Eds.). Springfield, Ill., Charles C Thomas, 1961, p. 258. 79. Markley, K., Gurmeudi, G., Chavey, P. M. and Bazan, A.: Fatal Pseudomonas septicemias in burned patients. Ann. Surg. 145: 175, 1957. 80. Meyers, R. S.: The misuse of antibacterials in inguinal herniorrhaphy. Surg. Gynec. & Obst. 108: 721, 1959. 81. Miles, A. A.: Nonspecific defense reactions in bacterial infections. Ann. New York Acad. Sc. 66: 356, 1956. 82. - - - and Niven, J. S. F.: Enhancement of infection during shock produced by bacterial toxins and other agents. Brit. J. Exper. Path. 31: 73, 1950.

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83. - - - , Miles, E. M. and Burke, J.: Value and duration of defense reactions of skin to primary lodgement of bactcria. Brit. J. Exper. Path. 38: 79, 1957. 84. Nahmias, A. J. and Eickhoff, T. C.: Medical Progress. Staphylococcal infections in hospitals. New England J. Med. 265: 77, 177, 1961. 85. Orie, N. G. M.: Bronchitis and right heart failure. Advances Cardiol. 2: 319, 1959. 86. Palmer, K. N. V. and Sellick, B. A.: Effect of procaine penicillin and breathing exercises on postoperative pulmonary complications. Lancet 1: 345, 1952. 87. Idem: Prevention of postoperative pulmonary atelectasis. Lancet 1: 164, 1953. 88. Panel. International integration of antibiotic sensitivity tests (Arnold Branch, Moderator). In press. Antimicrobial agents and chemotherapy, 1962. Proc. First Interscience Conference on Antimicrobial Agents and Chemotherapy. Ann Arbor, Braun-Brumfield, Inc. 89. Pearce, G. and Dineen, P. A.: A study of pseudomembranous enterocolitis. Am. J. Surg. 99: 292, 1960. 90. Petersdorf, R. G., Curtain, J. A., Hoeprich, P. D., Peeler, R. N. and Bennett, I. L., Jr.: A study of antibiotic prophylaxis in unconscious patients. New England J. Med. 257: 1001, 1958. 91. - - - and Merchant, R. K.: A study of antibiotic prophylaxis in patients with acute heart failure. New England J. Med. 260: 565, 1959. 92. Prohaska, J. V., Govostis, M. C. and Taubenhaus, M.: Postoperative pseudomembranous enterocolitis i successful treatment with corticotropin (ACTH). J.A.M.A. 154-: 320, 1954. 93. - - - , Jacobson, J. J., Drake, C. T. and Tan, T. L.: Staphylococcus enterotoxin enteritis. Surg. Gynec. & Obst. 109: 73, 1959. 94. - - - , Farrell, M. and Baker, W.: Pseudomembranous (staphylococcal) enterocolitis. Internat. Abstr. Surg. 112: 103, 1961. 95. Public Health Laboratory Service: The incidence of surgical wound infections in England and Wales. Lancet 2: 659, 1960. 96. Pulaski, E. J.: Chapter 3 in Christopher's Textbook of Surgery, 7th Ed. (Loyal Davis, Ed.). Philadelphia, W. B. Saunders Co., 1960, p. 42. 97. - - - , Mincks, J. R. and Beatty, G. L.: Acute appendicitis, tetracycline prophylaxis and wound infection. Antibiotic Med. & Clin. Therapy 8: 392, 1956. 98. Rabin, E. R., Graber, C. D., Vogel, E. H., Finkelstein, R. A. and Tumbusch, W. A.: Fatal Pseudomonas infection in burned patients. New England J. Med. 265: 1225, 1961. 99. Rittenburg, M. S., Hume, D. M. and Hench, M. E.: "Pathogen-free" patient care area. In abstract of papers presented at the Second Interscience Conference on Antimicrobial Agents and Chemotherapy, Oct. 31-Nov. 2,1962. To be published in Antimicrobial Agents and Chemotherapy, 1962. 100. Roberts, C. W., Jr., Perry, D. M., Keharic, H. A. and Kirby, W. M. M.: Demethylchlortetracycline and tetracycline. Arch. Int. Med.l0r: 204,1961. 101. Robinson, G. N., Stevens, S., Batchelor, F. R., Wood, J. C. and Chain, E. B.: Bacteriological studies on new penicillin-BRL 1241. Lancet 2: 564, 1960. 102. Robinson, J. R.: Surgical parotitis, a vanishing disease. Surgery 38: 703, 1955. 103. Rutenburg, A. N. and Greenberg, H. L.: Preliminary report on kanamycin 3-phenylsalicylate. In abstracts of papers presented at the Second Interscience Conference on Antimicrobial Agents and Chemotherapy, Oct. 31Nov. 2, 1962. To be published in Antimicrobial Agents and Chemotherapy, 1962. 104. Sabath, L., Postic, B. and Finland, M.: Methicillin treatment of severe staphylococcal disease. New England J. Med. 267: 1049, 1962. 105. Schatten, W. E.: Study of intraperitoneal antibiotic administration in the treatment of acute bacterial peritonitis. Surg. Gynec. & Obst. 102: 339, 1956. 106. Shackman, R. and Messent, D.: Effect of an indwelling catheter on the bacteriology of the male urethra and bladder. Brit. M. J. 2: 1009, 1954. 107. Sieber, H. G. and Hickam, J. B.: Carbon dioxide intoxication. The clinical syndrome, its etiology and management with particular reference to the use of mechanical respirators. Medicine 35: 389, 1956.

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108. Spratt, J. S., Jr.: Etiology and therapy of acute pyogenic parotitis. Surg. Gynec. & Obst. 112: 391, 1961. 109. Stein, M., Koata, G. M., Simon, M. and Frank, H. A.: Pulmonary evaluation of surgical patients. J.A.M.A. 181: 765, 1962. 110. Stewart, G. T.: Changes in sensitivity of staphylococd to methicillin. Brit. Med. J. 1: 863, 1961. 111. Tenney, B., Little, B. and Wamsteker, E.: Septic abortion. New England J. Med.257: 1022, 1957. 112. Tomsett, R.: Protection of pathogenic staphylococci by phagocytes. Tr. A. Am. Physicians 69: 84, 1956. 113. Weismann, R. E. and Twitchell, E. B.: Acute pseudomembranous enterocolitis in the postoperative patient. Ann. Surg. 32: 144, 191':6. 114. Wetterfors, J.: Subphrenic abscess. A clinical study of 101 cases. Acta elin. scandinav. 117: 388, 1959. 115. Williams, R. E. 0.: Epidemic staphylococci. Lancet 1: 190,1959. 116. - - - and others: Nasal staphylococci and sepsis in hospital patients. Brit. M. J. 2: 658, 1959. 750 Harrison Avenue Boston 18, Massachusetts (Dr. Howe)