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Acs0814 Clinical And Laboratory Diagnosis Of Infection

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  • 1. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 1 14 CLINICAL AND LABORATORY DIAGNOSIS OF INFECTION David C. Evans, M.D. and Jonathan L. Meakins, M.D., D.Sc. Approach to Diagnosis of Surgical Infection Surgical infection is a term that, though frequently used, is not Accordingly, several clinicians have used the term sepsis syn- clearly defined. In the strictest sense, it implies infection amenable drome to refer to the group of signs, symptoms, and physiologic to operative management through surgical source control, as in changes that result from a variety of sterile inflammatory process- the case of complicated diverticulitis or necrotizing soft tissue es as well as from systemic infection.2,4 The problem with using the infection. More generally, however, the term can refer to any infec- term in this way, however, is that it derives from a Greek word (sep- tion commonly seen in surgical patients (e.g., central line infection sis, “decay”) that implies infection with microorganisms. It is there- or postoperative pneumonia). Both definitions are pertinent, in fore not surprising that application of the term sepsis syndrome to that the same diagnostic principles apply in each situation. noninfectious settings has led to some confusion.5,6 The presence of surgical infectious disease is usually deter- To clarify the relevant terminology and provide a common ver- mined clinically and confirmed microbiologically. Identification of nacular with which to discuss surgical infection, the American College an infection is rarely incidental: most often it is sought in response of Chest Physicians and the Society of Critical Care Medicine held to a clinical signal. This signal is frequently fever but may be one a joint consensus conference in 1991 that led to the publication in or more of a number of other symptoms and signs. 1992 of the currently used terminology and definitions [see Sidebar Most surgical infections are outpatient conditions that are easi- Definitions of Key Concepts].7 A key outcome was the definition ly diagnosed and treated. Infections in hospitalized patients, of the nonspecific clinical picture of temperature, heart rate, respi- whether related to the primary surgical disease or resulting from ratory rate, and white blood cell (WBC) count abnormalities as the surgical therapy, are less easily managed. The greatest challenges systemic inflammatory response syndrome (SIRS). SIRS may or in diagnosis and treatment of surgical infections arise in the peri- may not be due to infection; when it is, it is referred to as sepsis.When operative and postoperative periods. sepsis results in organ dysfunction, the ensuing state is referred to as severe sepsis; when it results in persistent cardiovascular decom- pensation, the ensuing state is referred to as septic shock. Terminology Traditionally, the terms infection, sepsis, septicemia, bac- teremia, endotoxemia, and septic shock have borne similar conno- tations; this imprecision of terminology has led to considerable Definitions of Key Concepts confusion about the specific role of microbial infection as a cause • Systemic inflammatory response syndrome (SIRS): This response of the common clinical presentation of fever, tachycardia, and is manifested by the occurrence of two or more of the following occasional hypotension.The traditional tendency to conflate these conditions as a result of infection: (a) temperature higher than distinct concepts in this simplistic and unrefined manner has had 38° C (100.4° F) or lower than 36° C (96.8° F), (b) heart rate greater than 90 beats/min, (c) respiratory rate greater than 20 major implications for how antibiotics are used—or, more to the breaths/min or arterial carbon dioxide tension less than 32 mm point, misused—in surgical patients. Hg, and (d) white blood cell count greater than 12,000/mm3 or The human body’s physiologic response to systemic infection is less than 4,000/mm3, or immature (band) forms accounting for well characterized and is often referred to as sepsis. However, infec- more than 10% of the neutrophils present. tion and sepsis are distinct entities.The normal septic response to in- • Sepsis: SIRS when specifically caused by infection. • Severe sepsis: Sepsis associated with organ dysfunction, hypo- fection may, in fact, be completely absent in immunosuppressed pa- perfusion, or hypotension. Hypoperfusion and perfusion ab- tients. Most surgeons, for example, have encountered a patient normalities may include, but are not limited to, lactic acidosis, receiving high doses of steroids who has a perforated intra-abdomi- oliguria, or acute alteration of mental status. nal viscus and fecal peritonitis but whose leukocyte count, tempera- • Septic shock: Sepsis with hypotension despite adequate fluid resuscitation, with persistent perfusion abnormalities that may ture, and blood pressure are all normal. Conversely, a systemic inflam- include, but are not limited to, lactic acidosis, oliguria, or acute matory response mimicking sepsis may be present in noninfected alteration of mental status. Patients receiving inotropes or vaso- patients.1,2 For example, patients with acute pancreatitis, tissue pressors may not be hypotensive at the time perfusion abnor- necrosis, or fractures may manifest physiologic and metabolic malities are measured. changes that are indistinguishable from those associated with bac- • Multiple organ dysfunction syndrome (MODS): MODS is the presence of altered organ function in an acutely ill patient such teremia, even in the absence of infection. Animal studies have con- that homeostasis cannot be maintained without intervention. firmed that a sepsislike syndrome can occur without microbial inva- sion of host tissues.3
  • 2. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 2 Approach to Diagnosis of Surgical Infection Clinical signal of possible infection is noted Assess patient characteristics and circumstances of presentation: • Health of host • Intensity of physiologic response • Nature of pathogen Host status is assessed: normal vs. compromised/complex Response to infection in compromised or complex patients differs from that in normally responsive patients. Patient is normally responsive Patient is compromised or complex Risk factors include Cardinal signs of inflammation are • Advanced age • Major trauma • End-organ failure • Redness • Heat • Pain • Swelling • Loss of function • Thermal injury • Chemotherapy • ≥ 1 chronic disease Other signals include Cardinal signs may be present, but more often, infection is • New or persistent postoperative fever occult. Clinical manifestations may include • Tachypnea/tachycardia • Confusion • Ileus • Confusion • Ileus • Gastric bleeding • Intermittent hypotension and septic shock • Water retention • Delayed wound healing Laboratory signs of occult infection include • Renal, hepatic, or respiratory failure • Thrombocytosis or thrombocytopenia • Hyperglycemia and insulin resistance • Immune failure Patient is evaluated for presence of infection Begin with history and physical examination. Perform laboratory assessment: • Obtain Gram stain and cultures of wound tissue, sputum, urine, and drainage effluent • Consider percutaneous aspiration and microbiologic examination of potentially infected fluid • Obtain WBC and blood chemistry measurements • Obtain chest x-ray; consider imaging of operative site Therapy is initiated Treatment is governed by health of host, nature of response to infection (local vs. SIRS; mild sepsis vs. septic shock/MODS), and nature of pathogen (suspected or proven). Patient has SIRS or uncomplicated sepsis Patient has severe sepsis or is in septic shock Withhold antibiotics until definitive diagnosis is made, unless Simultaneously resuscitate, identify infectious focus, give patient is compromised or situation is urgent. empirical broad-sprectrum antibiotics, and undertake Restore homeostasis (give fluids). source control if able. Identify and control source of infection. Antibiotic choice should reflect (1) likely source of infection, (2) hospital- vs. community-acquired, (3) previous Identify pathogen and give suitable antibiotics. antibiotic therapy.
  • 3. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 3 Host Status: Normally Responsive Other versus Compromised or Complex Bacteremia That signs and symptoms of infection in compromised or complex patients differ Trauma from those in normally responsive hosts Fungemia has important diagnostic implications. Normally responsive patients, for whom Infection Sepsis SIRS the physician can obtain a history and per- Burns Parasitemia form a physical examination, respond to infection in the classic manner—typically, Viremia with fever, tachycardia, leukocytosis, malaise, and other appropri- Pancreatitis ate symptoms. For many reasons—even simply if the infection is Other severe—normally responsive patients may become compromised. Compromised or complex patients are unable to meet inflamma- tory or infectious challenges in the normal manner. Figure 1 Depicted are the interrelationships among infection, sep- Hence, the clinical signals of infection sis, and the systemic inflammatory response syndrome (SIRS). in such patients differ from those in normally responsive patients, often being absent or developing at a later stage of infection. Indeed, a multitude of clinical conditions or physiologic states define compromised or complex patients. These include the ex- tremes of age, immunosuppression as a result of either disease Clearly, SIRS includes all the signs, symptoms, and physiologic (e.g., HIV infection or lymphoma) or medication (e.g., chemo- changes characteristic of the sepsis syndrome; however, use of the therapy), thermal injury, major trauma, acute end-organ failure in term SIRS avoids the idea that such manifestations are necessarily the ICU, and the presence of more than one chronic disease.The the product of infection. Sepsis may be thought of as a special case of prevalence of such patients in modern hospital surgical practice is SIRS—SIRS associated with infection [see Figure 1].The term sepsis increasing steadily. syndrome, although very useful in guiding clinical thinking, is insuf- It must be kept in mind, however, that the normally responsive ficiently precise for our current needs and probably should no longer patient and the compromised or complex patient are merely be used.The term septicemia should not be used either. extreme points on the clinical spectrum rather than categorically The crucial point is that infection and sepsis are conceptually distinct populations. distinct: infection is a process, and sepsis is the response to that process. The response provides the clinical signals that lead to diagnosis of the initiating process. As a rule, infection, once diag- Physiologic Response to Infection nosed, is easily treated with antibiotics and drainage. It is the man- agement of sepsis that is difficult [see 8:13 Multiple Organ Dysfunc- NORMALLY RESPONSIVE PATIENTS tion Syndrome]. Cardinal Signs of Inflammation Rubor, calor, dolor, tumor, and functio General Approach to Diagnosis of laesa—that is, redness, heat, pain, swelling, Infection and loss of function—have been consid- The search for an infection is prompted ered the cardinal signs of localized inflam- by a clinical signal indicating a problem in mation since the times of Hippocrates and need of resolution [see Table 1]. The signal Galen. They remain the primary signals denotes the response of a patient to an leading to medical consultation for outpatient surgical infections infectious stimulus and is a function of the and for many of the infectious complications of operation. They patient’s physiologic ability to react to the are emblematic of the host’s effort to contain infection locally and endogenous and exogenous mediators lib- may signal the presence of infection even in cases where the pri- erated through the infectious process. A mary site of infection is a deeply situated organ or tissue. thorough history and physical examination are imperative and Infections amenable to surgical intervention may present in this should be followed by selected laboratory tests. Normally respon- way; however, nosocomial infections complicating the course of sive patients tend to show the classic signals, whereas compro- surgical patients are generally signaled in more subtle ways. mised or complex patients often show more subtle signs that may only be noted as abnormalities on routine bloodwork. Fever The diagnostic approach to suspected infection must be modi- Fever is perhaps the most common signal that an infectious fied according to patient characteristics and the circumstances of process is present. presentation; for example, the specific differential diagnosis for Postoperative fever is a normal part of the recovery process; under- infection appearing on postoperative day 1 will clearly be different standing the typical febrile course is important in differentiating from that for infection appearing after 1 week in the ICU. There normal from pathologic fever. It is unusual for a sudden, very high are three important elements at play when a surgical patient expe- fever to be the first signal of an infection. Infection usually begins riences an infection: (1) the health of the host, (2) the intensity of to manifest itself with a prodrome, recognition of which speeds the physiologic response to infection, and (3) the nature of the diagnosis and therapy. Investigation should be started when the pathogen. All three factors must be considered carefully in the patient’s temperature reaches 38° C (100.4° F) rather than 40° C diagnosis of surgical infection. (104° F). Although this point may seem obvious, many of the cri-
  • 4. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 4 ferred, and the painful area appears normal on examination. Pneu- Table 1 Fundamental Approach to monia that presents with abdominal findings is a classic example, as is the shoulder-tip pain with a normal range of motion seen in Diagnosis of Infection patients with a subphrenic abscess. Recognize clinical signal and observe its characteristics: Nature Confusion Confusion is a common symptom of infection in Intensity the elderly; it is also an important signal in patients who had been Rapidity of development well and fit.The physician’s first response to confusion in an elder- ly patient in the postoperative period must be to seek a cause, not Make best guess as to source and likely pathogen on the basis of to order sedation. History of surgical disease Physical examination Microbiologic examination of stained specimens Ileus Ileus has many causes, some of which are not well Radiologic findings understood. Prolonged ileus after abdominal operation—as well as almost any ileus after other operations—requires explanation. Confirm presence of infection by means of Infections at remote sites (e.g., SSI and pneumonia) can produce Laboratory results ileus, as if the bowel were a target organ such as the kidney, the Observation of clinical course liver, or the lung. Invasive procedures (e.g., paracentesis, thoracentesis, interventional radiology, operation) COMPROMISED OR COMPLEX PATIENTS The presence of fever remains a common signal of infection in the compromised or sis intervention measures required in managing fevers could be complex patient; however, it may be absent, avoided if the significance of more modest temperature elevations or the patient’s temperature may already be were recognized more often. elevated as a result of other causes. Cardinal A fever that appears after the normal postoperative temperature signs of infection may be present. More of- elevation has resolved must not be ignored.To simply wait for such ten, however, the infection is occult, and a fever to dissipate is to court disaster. In the absence of a clear classic signals are unrelated to the infectious diagnosis, a thorough physical examination of the patient, direct- focus. In some very ill immunocompro- ed by laboratory tests and followed by reexamination as necessary, mised patients, findings that usually signal an infection may already is required to identify occult infection. be present. Slight changes in clinical status (e.g., minor temperature elevations, increased fluid requirements, confusion, and ileus) or Miscellaneous Signals changes in laboratory findings (e.g., an elevated WBC count, gluco- It is common wisdom that the signals communicating under- suria, and hyperglycemia) should trigger investigation. lying infection in the compromised or complex host may be sub- Patients in whom the first signal of an infectious process is organ tle.The astute clinician will be in tune with these and, with expe- dysfunction or failure, rather than fever and tachycardia, are likely to rience, will recognize when to undertake a diligent search for be physiologically compromised and seriously ill; perhaps more im- infection. portant, however, is that they are a group whose diagnosis and man- agement require expert clinical skills. Because the classic septic re- Altered heart rate A heart rate that is either too high or too sponse may not be present, it is essential to be alert to the signs and low may signal an infection. On rare occasions, a change in rhythm symptoms of occult infection (see below). In these patients, the labo- in the elderly (e.g., paroxysmal atrial tachycardia, flutter, or atrial ratory and the radiology suite become increasingly important in di- fibrillation) indicates an infectious process. Gram-negative sepsis agnosing and documenting the evolution of the infection. may produce a so-called relative bradycardia, meaning that the resulting tachycardia is not as pronounced as one might expect. Clinical Signs and Symptoms of Occult Infection An unexplained sustained increase in heart rate should not be Subtle changes in temperature, mental status, pulse rate, or res- ignored. piratory rate may signal occult infection, as may the development of pain or ileus. Tachypnea Whereas tachypnea occurs commonly after oper- ation in response to pain or poor pulmonary toilet, it may also sig- Intermittent hypotension and septic shock Septic shock, nal either the prodrome of infection or the onset of SIRS. Because an important manifestation of an unrecognized focus of infection, tachypnea may herald not only infection but also other important is the original expression of multisystem failure. Fortunately, diagnoses (e.g., pulmonary embolism), it must be thoughtfully it rarely occurs without warning. The prodrome often includes and methodically evaluated. fever and sometimes other signals. Recurring hypotension is the most characteristic signal; it usually is not catastrophic and Pain Pain that persists or is out of proportion to the expect- responds quickly to fluid resuscitation. Oliguria may accompany ed response deserves attention. Whenever a surgical wound that the hypotension. If this clinical state is allowed to progress, the was healing favorably for the first 5 to 7 days becomes more hypotension will lead to renal failure (see below), with substantial painful, a deep surgical site infection (SSI) must be suspected and water retention. Septic shock will result if the infection is not iden- ruled out, even if other signs are absent. Unexplained muscular tified and treated with appropriate antibiotics and source control pain is often the first harbinger of deadly necrotizing soft tissue as necessary. infection caused by gram-positive bacteria (e.g., group A strepto- Both clinical assessment and laboratory studies are necessary cocci), the early recognition of which may be lifesaving and limb- to confirm the presence of septic shock, although florid septic preserving [see 3:2 Soft Tissue Infection]. Sometimes pain is re- shock is easily recognized on clinical examination alone [see 8:3
  • 5. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 5 Shock]. Any or all of the following findings may be present in vary- immunosuppressive. The most clinically applicable measure of ing degrees: tachycardia; tachypnea; hypotension; warm, dry ex- immune failure at present is probably delayed wound healing. tremities; generalized flushing; and other signs suggesting a hyper- dynamic, hypermetabolic state. Swan-Ganz catheter measure- ments confirm high cardiac output and low peripheral vascular Evaluation for Presence of Infection resistance. Once the surgeon has evaluated in which ways the patient may be compro- Gastric hemorrhage Gastric hemorrhage may be the present- mised or susceptible to infection and to ing symptom of serious infection even if prophylactic measures which degree the physiologic response is against such hemorrhage have been taken. It is particularly sugges- inappropriate or harmful (i.e., provokes tive of perigastric abscess resulting from anastomotic leakage after multiple organ dysfunction or shock), then upper abdominal surgery. Gastric hyperacidity and bleeding general- it is important to consider which microor- ly respond to drainage of an abscess. Hemorrhagic gastritis must al- ganisms might be responsible for the pre- ways be considered a signal of occult infection, which demands senting clinical picture.This obviously varies prompt diagnosis and treatment. with the clinical situation and requires knowledge of specific con- dition-associated pathogens, as well as the prevalence of certain Delayed wound healing The absence of wound healing can pathogens in a particular hospital or ICU. indicate the presence of a significant infection. Typically in such a The prevalence of resistant bacterial strains should be moni- case, wounds left for delayed primary closure or secondary closure tored in clinical settings in order to guide empirical therapy. do not exhibit the appropriate granulation tissue and appear pale, Methicillin-resistant Staphylococcus aureus (MRSA), once an occa- dry, and unhealthy.The development of good granulation tissue is sional finding, has become so common in some ICUs and chron- a sign that infection is controlled. ic wards that surveillance and isolation programs are no longer employed. It is now the rule for extensive invasive monitoring and Laboratory Signs of Occult Infection access devices to be used in the care of critically ill patients, who Renal failure Renal failure [see 8:6 Renal Failure] is identi- thereby become particularly predisposed to gram-positive infec- fied by elevations in serum creatinine and blood urea nitrogen tion; accordingly, it is important to appreciate the likelihood that (BUN) levels, which can be highly sensitive signals of developing MRSA will be encountered. The same is true of Pseudomonas infection. A still more sensitive indicator is an alteration in creati- aeruginosa, a ubiquitous commensal and a common gram-nega- nine clearance, a laboratory test underutilized in the ICU. Such tive pathogen in hospitals. In compromised patients exposed to alterations are generally evident before changes in serum levels. multiple antibiotics, P aeruginosa readily acquires antibiotic resis- . Creatinine clearance should be measured at an early stage in high- tance that usually necessitates the use of double-agent or broad- risk patients. In the presence of shock, renal failure can develop spectrum coverage for effective management. suddenly. Otherwise, loss of renal function is insidious, but it can Recognizing the virulence of certain pathogens is as important usually be identified if sought before oliguria or anuria develops. as appreciating their antibiotic susceptibilities. Enteroinvasive Resolution of infection is associated with return of function. Escherichia coli 0157-H7, for example, may cause a rapidly pro- gressive hemorrhagic enteritis and provoke a fatal septic syndrome Hepatic and respiratory failure Hepatic failure [see 8:9 marked by acute renal failure, bleeding, and coma. Necrotizing Hepatic Failure], primarily manifested as jaundice, and respiratory soft tissue infections, particularly when caused by gram-positive failure, initially presenting as a organisms, may be precipitously fatal. Early Gram stain microscopy falling arterial oxygen tension and subsequently marked by a need to identify the specific pathogen is a critical step in the manage- for mechanical ventilation or by a change in the fraction of ment of this condition. inspired oxygen (FIO2) requirement, can behave in the same way Essentially the same clinical and laboratory assessments are as renal failure (i.e., with drainage and control of infection leading used to evaluate normally responsive and compromised or com- to restoration of function). plex patients for the presence of infection.There is, however, a sig- nificant difference in emphasis. In normally responsive patients, Abnormal platelet count Thrombocytosis is often seen in the diagnosis of infection is usually made on clinical grounds with association with infection, particularly with compromised hosts, in laboratory support, whereas in compromised or complex patients, whom the infection may be occult. Thrombocytopenia may also the diagnosis is usually made on the basis of laboratory findings indicate serious infection, though it is not a common signal.When with clinical support. this occurs in the context of sepsis, it is either because disseminat- The ICU patient presents a particular conundrum. Nosocomial ed intravascular coagulation (DIC) has developed or because infection is identified in an estimated 20% of such patients.8 there is a diminution of all blood lines indicating marrow dys- Despite the frequency with which it is suspected and reported, it function. The cause of any abnormal platelet count should be is difficult to prove unequivocally. The perceived prevalence of identified promptly if possible. nosocomial infection has created a strong predisposition toward instituting empirical antibiotic therapy in ICU patients; however, Hyperglycemia and insulin resistance Hyperglycemia the global value of this action in terms of both patient outcome and insulin resistance are often reliable signals of the presence of and the impact on the ecology of the ICU is unconfirmed and infection in diabetic patients as well as in nondiabetic patients.The requires validation. The enormous inconsistencies in how infec- degree of insulin resistance can reflect the severity of the infection tions are diagnosed have a tremendous effect on our ability to as well as the effectiveness of infection control. assess the efficacy of therapy for infection. The current approach to diagnosing infection in surgical patients, particularly those who Immune failure Immune failure is discussed in detail else- are critically ill or compromised, is still in great need of clarifica- where. Severe infection is tion and standardization.9 Until these issues are resolved, the clin-
  • 6. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 6 ician must be familiar with the strengths and limitations of a vari- found to be significantly elevated in patients with pulmonary aspira- ety of current diagnostic methodologies and then exercise tion that has induced bacterial infection, compared with patients thoughtfulness and disciplined diligence.The likelihood that a par- with sterile pneumonitis.12 Some investigators have suggested that ticular patient is infected (i.e., the pretest probability) is as impor- because CRP concentration appears to be particularly responsive to tant in the decision to treat as the fulfillment of any particular con- bacterial infection, it may be useful as a monitor of the efficacy of an- stellation of diagnostic criteria. tibiotic use, thereby guiding discontinuance of treatment.13 A host of cytokines, cellular adhesion molecules, oxidants, and other biomole- HISTORY AND PHYSICAL EXAMINATION cules known to participate in systemic inflammation from numerous The history should include all comorbid conditions (e.g., dia- causes are being extensively investigated to establish both diagnostic betes, lung disease, cirrhosis, hepatitis, kidney disease necessitating and therapeutic functions [see 8:26 Molecular and Cellular Mediators dialysis, and previous important infections) as well as a hospital- of the Inflammatory Response]. As yet, however, no single mediator of ization history that covers health status, surgical diagnosis and systemic inflammation has been validated as a reliable clinical tool therapy, additional therapeutic interventions (including interven- for surveillance of the progression of infection or the response of in- tional radiology, monitoring devices, drains, and drugs), and other fection to treatment. related variables. In the early postoperative period (3 to 6 days after operation), the traditional causes of the signals of infection have their origin in the wound, intravascular lines, the urinary tract, and the lungs. Deep thrombophlebitis, with or without pulmonary embolism, may also initiate a systemic inflammatory response that mimics Case Study: Clinical Picture of Sepsis without sepsis.The general physical examination is often unrewarding, but Infection a number of specific examinations should be carefully performed, Infection is a process; sepsis is the response. with emphasis given to (1) all wounds and surgical sites, (2) all invasive monitoring or therapeutic devices and surrounding areas The difficulty of managing the patient who manifests the septic re- sponse in the absence of infection is illustrated by the following case. (notably central and peripheral I.V. lines), (3) all drainage systems A 55-year-old insulin-dependent man with peripheral vascular and surrounding tissue, with particular attention paid to the disease presented with evidence of infection in both feet. nature of the drainage and whether it has recently changed in Hydration and antibiotic therapy did not prevent progression of the character or volume (particularly if it has stopped), (4) the rectal infection, and within 18 hours, it was apparent that amputation would be required for source control. In the course of the opera- examination (for pelvic or prostatic infection), (5) areas of poten- tion, gas gangrene, more extensive than had been clinically sus- tial decubitus ulcers, (6) the neck (for CNS infection), (7) pected, was discovered. The initial below-the-knee amputations intravascular lines, surrounding tissue, and proximal vessels, (8) were eventually followed by a hip disarticulation on one side and a the lungs, and (9) the legs.The physical examination is important high above-the-knee amputation on the other. Over the 36-hour as a guide for selecting specimens for microbiologic analysis, par- period during which the infectious process was being controlled, classic septic shock, renal failure, coma, and respiratory failure ticularly when there have recently been significant changes in developed. There was no change in the patient’s hyperdynamic wounds or drainage. The decision to seek radiologic consultation and hypermetabolic state after the amputations. During the next may depend on the findings on physical examination. 3 weeks, he required ventilator support and daily hemodialysis or hemofiltration; became jaundiced and more deeply comatose; DIAGNOSTIC TESTS received fluids in amounts significantly in excess of output to main- tain blood volume; was hyperglycemic despite receiving regular insulin in dosages of 3 to 5 U/hr; and remained in a hyperdynamic Hematologic and Biochemical Tests state. Shortly after the last operation, an ileus developed, accom- After physical assessment, laboratory blood tests are routinely panied by gross fluid retention, which further increased the relied on to orient the surgeon toward or away from a clinical patient’s girth. This state of overt sepsis with hypermetabolism per- sisted while the wounds healed by primary closure, but no focus of diagnosis of infection. Leukocytosis, particularly with an infection could be found. increase in band forms, is a usual but inconsistent marker for Antibiotic therapy was stopped for 10 days after operation; the infection. The WBC count is widely used to follow the response patient’s clinical status did not change. Frequent searches were of infection to therapy and thus has been adopted as a surrogate made to ensure that no infection had been overlooked. Sug- gestions—seriously put forward—to explore the patient’s abdomen indicator of the success or failure of therapy. Surprisingly, how- because “there must be something there” were not heeded. At the ever, the documentation supporting this ubiquitous practice is end of the third week, for no obvious reason, the patient started to sparse.10,11 Not only is the daily series of complete blood counts urinate, his ileus resolved, and he was gradually weaned from often ordered in conjunction with the initiation of antibiotic the ventilator. His level of consciousness improved, the massive therapy wasteful and unpleasant for the patient, but it also typi- edema cleared, and the high cardiac output and low peripheral resistance resolved over a period of 72 hours. He was discharged cally tells the clinician little about the clinical course that cannot from the surgical ICU 1 day later and from the hospital in 3 weeks. be gleaned at the bedside. Some noninfectious process that had maintained this patient’s per- In more complex surgical patients, other biochemical cues are sistent septic response had disappeared or had been turned off, used to varying degrees as means of assessing the likelihood of infec- and the result was rapid resolution of the septic state and recovery of health. tion. In addition to thrombocytosis, thrombocytopenia, hyper- As noted, initial control of infection, though difficult, was glycemia, and metabolic acidosis, which commonly reflect the stress achieved relatively early. Subsequent therapeutic efforts involved of severe infection, changes in the erythrocyte sedimentation rate providing hemodynamic, metabolic, and physiologic support of (ESR) and in blood levels of C-reactive protein (CRP), procalcitonin the patient’s failing organs and organ systems while waiting for the (PCT), interleukin-6 (IL-6), and tumor necrosis factor (TNF) have septic response to resolve. The real problem in this case was not the infection but the patient’s unremitting septic response, which a significant association with the presence of clinical infection. Plas- was initiated by the infection but maintained in its absence. ma CRP concentration, which has been extensively used in some European countries to monitor the evolution of infection, has been
  • 7. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 7 Microbiologic Studies SIRS As a rule, Gram stains and cultures of wound tissue, sputum, As mentioned, SIRS was specifically defined in such a way as to urine, and drainage effluent are useful studies. In some cases, a bat- emphasize that this common clinical syndrome frequently occurs tery of cultures of potential sites of infection may be the only feasible without infection and does not routinely necessitate treatment, approach. Culture techniques are discussed more thoroughly else- especially with empirical antibiotic therapy. As an illustration, sim- where [see 8:27 Blood Cultures and Infection in the Patient with the Sep- ply climbing a set of stairs is often enough to enable a healthy indi- tic Response and 8:16 Nosocomial Infection]. vidual to fulfill the diagnostic criteria for SIRS—albeit briefly. The use of polymerase chain reaction (PCR) technology to detect The point that SIRS is not invariably associated with microbial bacterial DNA is emerging as a useful alternative to microbiologic invasion is especially relevant to critically ill and traumatized ICU culture for determining the presence of infection. PCR identifies and patients, in whom it is not uncommon for clinical signs and symp- amplifies a specific bacterial DNA sequence by means of a chemical toms indistinguishable from those of severe sepsis to arise or per- proliferation process that may take no longer than a few hours. Un- sist in the absence of any infection [see Sidebar Case Study: fortunately, the sensitivity and specificity of this powerful technique Clinical Picture of Sepsis without Infection]. Burn injury and pan- is highly variable. Although investigations have shown PCR to be a creatitis are classic examples of conditions that can provoke such sensitive method of confirming the presence of bacteria in the blood a response: both can give rise to a hyperdynamic, hypermetabolic of clinically septic ICU patients,14 comparison of PCR results with clinical picture identical to that of sepsis or severe sepsis, even blood culture results is problematic in that nonviable bacteria or bac- when no infection is present. Surgeons have learned not to give terial debris are likely to create false positive results, leaving the clini- antibiotics unless there is evidence of infection. The instinctive cian uncertain as to whether treatment is indicated.The accuracy of reflex to do something must be held in check: “masterful inactivi- PCR thus remains to be established, but the rapidity with which it ty” is the appropriate response until a specific source that can be yields results makes it highly promising as a potential guide to thera- controlled is identified. peutic intervention. UNCOMPLICATED SEPSIS Radiology The approach to treatment of infection in both normally respon- A chest x-ray is mandatory. Ultrasonographic examination of the sive and compromised patients with mild to moderate sepsis in- operative site may be useful to evaluate the possibility of a deep ab- cludes five steps: (1) resuscitation and reestablishment of homeosta- scess. Computed tomography of the operative site is often more use- sis and organ function, if necessary; (2) identification of the focus of ful than ultrasonography because the presence of wounds, dressings, infection by clinical or radiologic examination; (3) source control, and drainage tubes may obscure ultrasonographic findings.The pos- which implies removal, containment or control of the infectious fo- sibility of acalculous cholecystitis must be kept in mind, though this cus (e.g., open drainage of an infected wound; resection of compro- is probably an overdiagnosed entity of unvalidated clinical signifi- mised bowel, as for appendicitis or advanced diverticulitis; or percu- cance. taneous drainage, as for pancreatic abscess); (4) microbiologic In compromised or complex patients who have not recently undergone an operation, the medical and surgical histo- characterization of the offending pathogen by means of culture, ry combined with the radiologic examination may be the only guide Gram stain, or both; and (5) empirical or targeted treatment with to the potential infectious focus (e.g., ulcer, diverticulitis, cholecysti- antibiotics, depending on the clinical urgency. tis or cholangitis, or obstructed ureter). Percutaneous aspiration of In compromised patients, empirical antibiotic therapy is often potentially infected fluid should be considered, and this fluid should started before diagnosis, and its efficacy gauged by the patient’s be microbiologically examined if possible. subsequent clinical course [see Discussion, below]. In normal hosts with uncomplicated sepsis, many would consider it appropriate to withhold empirical therapy until source control has been effected Institution of Therapy and the pathogen or pathogens characterized. Adequate source As noted, the response to infection occu- control, when possible, is often all that is required for successful pies a continuum ranging from virtually no management of sepsis, particularly in healthy hosts. In such cases, clinical expression in the immunosup- antibiotic use for prophylaxis against complications such as SSIs is pressed patient to full-blown septic shock. of proven benefit; however, there actually is little evidence to indi- Sepsis, in its basic form, represents a mild cate that antibiotics are necessary to treat sepsis if mechanical to moderate response to infection that source control has been definitively achieved. occurs in normally responsive patients as Antibiotic Treatment well as in many compromised or complex patients. On the basis of the results of clin- In the absence of convincing culture data, antibiotic treatment ical or laboratory tests, the clinician can evaluate the magnitude of must be directed against a likely cause, as determined by recent the septic response and thus its clinical gravity. history (particularly procedures), past history, and physical exam- It is therefore the magnitude of the host response, in combina- ination. Examples of likely causes are (1) urinary manipulation, tion with the health of the patient and the nature of the likely which necessitates coverage against enterococci and gram-nega- infecting organism, that directs the clinician’s approach to therapy. tive bacteria with ampicillin and an aminoglycoside; (2) colonic The greater the degree of sepsis, the greater the clinical urgency of flora, which mandates wide coverage against anaerobes and aer- solving the two fundamental problems involved: resolution of the obes; (3) infected vascular lines, which warrant coverage against initiating process (i.e., treatment of the infection) and modulation gram-positive organisms; (4) cholangitis, which calls for coverage of the response to that process (i.e., management of sepsis) [see against aerobic gram-negative bacteria with ceftriaxone or an 8:13 Multiple Organ Dysfunction Syndrome]. The therapeutic aminoglycoside; and (5) pneumonia, which necessitates coverage approach to a given patient is based on the need for speed. against gram-positive and gram-negative aerobes.
  • 8. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 8 Drainage SEVERE SEPSIS AND SEPTIC SHOCK The search for the focus of infection is important because For assessment and management of se- drainage may resolve the entire problem. The clinical state can vere sepsis and septic shock [see Sidebar be changed dramatically by technical or mechanical manage- Definitions of Key Concepts], the four ment of pus behind an obstruction (e.g., in the biliary tree, the steps in treatment—resuscitation, diagno- urinary tract, or the tracheobronchial tree) or pus under pres- sis of the infectious focus, antibiotic thera- sure (e.g., an abscess), by manipulation of a drain, or by py, and drainage—must be performed removal of a foreign body (e.g., an intravascular line). Prompt concurrently. Specifically, I.V. administra- elimination of all foci of infection that can be drained or are tion of empirical antibiotics must be initi- operable is critical. Needle aspiration of peritoneal or pleural ated promptly, before the diagnostic fluid may be very helpful. Wounds must be reevaluated con- process is completed, and any potentially drainable focus must be stantly and the presence of pressure sores ruled out. Drainage identified via physical examination or radiologic imaging. The can often be performed either percutaneously (e.g., for choice of antibiotic depends on (1) what the likely source of infec- pyelonephritis from ureteral obstruction or for subphrenic tion is (e.g., a lung, a perforated viscus, or the biliary tract), (2) abscess) or endoscopically (e.g., for cholangitis). Antibiotics whether the infection is hospital acquired (in which case antibiot- alone may suffice to treat small collections not accessible by ic resistance must be considered), and (3) whether the patient has means of percutaneous techniques. previously received antibiotic therapy. Discussion Approaches to Specific Infections in Complex Surgical nary tract infection (UTI).8 Bacteria adhere to urinary catheter Patients surfaces, where they promote growth of a so-called biofilm com- The following infections may occur in all surgical patients.They posed of microorganisms, bacterial glycocalices, Tamm-Horsfall are, however, much more difficult to identify in complex surgical protein, and urinary salts. Eradication of this infectious nidus is patients, such as those admitted to the ICU. Because the signals of essentially impossible without catheter removal.16 The standard infection are less specific and extremely difficult to interpret after criterion for the diagnosis of UTI (105 bacteria/ml) is difficult to injury or operation, the approach to diagnosing and treating infec- apply in catheterized patients because antibiotic therapy without tion must be cautious and disciplined. removal of the catheter and the source of bacteriuria would be ineffective. Furthermore, it is well established that urine cultures SURGICAL SITE INFECTION demonstrating as few as 101 or 102 bacteria/ml increase 1,000-fold SSIs include all infections occurring within the operative field, within 1 to 2 days17; effectively, therefore, any bacterial growth on from the skin to the actual area of surgery [see 1:1 Prevention of a urine culture from a catheterized patient signals heavy coloniza- Postoperative Infection].15 The patient history should address previ- tion, if not infection. ous diseases as well as issues concerning the operation itself, such More important than quantifying the degree of bacteriuria is as wound risk classification, duration, difficulty, urgency, use of determining whether there is any evidence of tissue invasion by drains, other details of the procedure, time elapsed since the oper- urinary bacteria, which would present as pyelonephritis, cystitis, ation, and whether the patient was immunosuppressed, experi- prostatitis, epididymitis, bacteremia, or sepsis. The patient history enced trauma, or received chemotherapy. Physical examination should determine whether a Foley catheter was used and for how should focus on the cardinal signs of infection and the absence or long; how, when, and why it was inserted; instrumentation (e.g., a presence of a healing ridge. so-called in-and-out catheter, cystoscopy, or transurethral resec- Deeper infections tend to become apparent later in the postop- tion of the prostate); and whether the patient has had any previous erative course, often after a period in which the patient appears to UTIs. The physical examination should ascertain whether there is be recovering, and are associated with a variety of signals, some of any costovertebral angle tenderness or evidence of prostatic or epi- which can appear suddenly.The physical examination is often use- didymal tenderness. less or misleading because of discomfort associated with the oper- Laboratory tests should include gross and microscopic urinaly- ation. Surgical site pain that increases or fails to resolve in the 7 to sis, urine culture, and sensitivity tests. Blood culture is important 10 days following surgery is an important yet subtle marker for because it may substantiate the diagnosis, identify the bacteria pres- occult infection that calls for investigation. Rectal examination is ent, and determine the degree of invasiveness of the infectious important because it may detect abscess formation or bleeding. process. Return of ileus after an abdominal operation is a significant clue to the presence of abdominal infection. VASCULAR CATHETER INFECTION Culture is essential because use of the correct antibiotics is par- The most frequent sites of infection postoperatively are I.V. ticularly vital in treatment of compromised or complex patients. catheters, particularly peripheral ones. Diagnosis of peripheral Knowledge of the organism and its sensitivities is the key to iden- catheter infection is simple and is made on clinical grounds. tifying epidemic or multiresistant strains. Diagnosis of central venous catheter (CVC) infection is more dif- ficult. Because hospitalized patients are increasingly being man- URINARY TRACT INFECTION aged with monitoring or therapeutic modalities that depend on Nearly all patients admitted to the ICU have a urinary catheter vascular access (e.g., total parenteral nutrition and dialysis), line in place; of these, it is estimated that about 20% progress to uri- infections have become more common, with an incidence ranging
  • 9. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 9 from two to 30 infections per 1,000 CVC days.18 The combined same group of patients.) Because maxillary or frontal area tender- pressures imposed by (1) the need to maintain vascular access in ness is nonspecific in very ill surgical patients, the diagnosis is usu- sicker and more complex patients and (2) the increasing predom- ally based on CT demonstration of sinus opacification or air-fluid inance of gram-positive CVC infections observed since the late levels. As a first step, sinus drainage should be reestablished by 1970s have led clinicians in many centers to administer empirical removal of an unnecessary nasogastric tube. Some authorities therapy without line removal to complex patients as a matter of advocate sinus aspiration for culture before empirical antibiotic course; some even advocate 10 to 21 days of vancomycin-based therapy is begun in urgent cases. therapy. The problems associated with the latter approach— PAROTITIS emerging vancomycin resistance, nephrotoxicity, and rash—are serious and relate specifically to the diagnostic strategy used to Parotitis is an increasingly common clinical diagnosis in elderly manage potential CVC infections. Distinguishing between contam- patients. It is usually caused by S. aureus and diagnosed on the ination, colonization, and true infection is problematic; as a result, basis of the presence of the classic local signs of inflammation. a number of diagnostic strategies have been advocated that are Culture of Stensen’s duct and blood culture are useful. predicated more on practicality and cost-effectiveness than on PROSTATITIS microbiologic reality. It is believed that CVC infection most commonly arises from Prostatitis (diagnosed by rectal examination) and epididymitis invasion by skin microorganisms (S. aureus or S. epidermidis in are clinical expressions of Foley catheter–related infection.The aid about 80% of cases), which may manifest itself as exit-site puru- of prostatic massage is important in obtaining specimens for cul- lence with or without local cellulitis, as a tunnel infection that may ture. It should be remembered that a blocked Foley catheter is the be clinically difficult to detect, or as catheter-related bloodstream most common cause of hospital anuria. This obstruction can lead infection (CR-BSI). Of these, CR-BSI, which complicates as many to devastating purulent cystitis and upper UTI. as 5% of line placements, is the most clinically important entity. It PSEUDOMEMBRANOUS ENTEROCOLITIS is strictly diagnosed by identification of the same microorganism (identical species and antibiogram) grown from both the catheter Antibiotic-associated pseudomembranous enterocolitis is diag- and a peripheral blood culture. nosed by obtaining specimens for serology and culture and per- The catheter may be cultured in one of several ways, the most forming proctosigmoidoscopy. Clostridium difficile is frequently common of which is the roll-plate method [see 8:16 Nosocomial In- identified as the causative pathogen. Although pseudomembran- fection]. Because it is theoretically possible that this technique may fail ous colitis is rarely clinically impressive and is easy to overlook, it to detect bacteria harbored within the catheter lumen, some authori- can be rapidly fatal. Initial appropriate antibiotic therapy is not ties advocate the more sensitive sonication method, in which the always successful; therefore, reevaluation at the end of the treat- catheter segment is immersed and agitated in a medium to produce a ment course is required. broth that contains bacteria from both the internal and the external surfaces of the line.This technique is both more costly and more time consuming, in that it requires quantitative cultures that are deemed Problems with Empirical Treatment of Infection positive only when more than 103 colony-forming units are detected. The frequent presence of SIRS in complex or critically ill surgi- More often, blood drawn through the CVC or cultured from an exit- cal patients usually prompts a reflexive response to “pan-culture” site exudate is compared with peripheral cultures, and thus there is the patient if no credible source of infection is apparent.When per- no need to remove the line. If quantitative cultures are done, a line missive or loose diagnostic criteria for infection are invoked, the blood culture showing five to 10 times more growth than the periph- inevitable result is the commencement of empirical antibiotic ther- eral sample strongly suggests that the catheter is the source of the apy for suspected infection, which is often, by default, continued bacteremia. A less costly method that renders quantitative cultures for days, if not weeks, pending definitive culture results or clinical unnecessary relies on the speed of bacterial growth: if growth in improvement. This strategy may seem reasonable and is under- catheter-drawn blood is faster than that in peripherally drawn blood, standably difficult to resist, but it is potentially deleterious in many a primary line infection is likely. On its own, a line blood culture is ways, and there are many sound objections to its reflexive use.21 not sensitive or specific enough to be diagnostically useful. Empirical antibiotic therapy can obfuscate future cultures, pre- dispose to the emergence of resistant organisms (which are associ- PULMONARY INFECTION ated with increased attributable mortality), promote derepression Diagnosis and management of nosocomial pneumonia in surgical of homeostasis-maintaining endogenous flora, cause toxic reac- patients is addressed in detail elsewhere, tions and secondary effects, alter the ecology of the unit in which The central issue is that there is no universal agreement it is used (as shown by the rising prevalence of MRSA and van- as to how pneumonia—particularly ventilator-associated pneumo- comycin-resistant enterococci in both European and North nia—should be diagnosed. Of the innumerable diagnostic options, American centers), and raise the cost of patient care. This widely none can rely on demonstration of tissue invasion by microorgan- used strategy is largely unvalidated.10,11 It must be emphasized that isms, as would be ideal: all are to some degree nonspecific, and any the paramount principle of therapy for infection is treatment may be invoked to justify initiation of antibiotic therapy.19 Random- focused on appropriate microbiologic cultures in the context of ized trials linking mode of diagnosis to therapeutic strategy and then strict diagnostic criteria for infection. to outcome are yet to resolve this issue.20 Many authorities espouse streamlining of empirically begun broad-spectrum antibiotic therapy in response to microbiologic SINUSITIS data once culture results are available; however, it is frequently dif- All patients undergoing prolonged nasogastric intubation are ficult to discontinue antibiotics once they have been started.When predisposed to sinus infection. Previous facial trauma and a histo- strict diagnostic criteria for infection are not met or, more impor- ry of sinusitis are potential contributing factors as well. (Otitis and tant, when antibiotic therapy based on nonmicrobiologic evidence pharyngitis, which are not often considered, occur in much the of infection yields negligible results, strong consideration should be
  • 10. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 10 given to stopping the antibiotics, and an exhaustive effort should be it may also resolve completely on its own. What actually consti- made to identify and control any occult persistent cause of the tutes adequate source control and how this can be measured are inflammatory state. Of course, this is easier said than done. More- critical questions and remain the subject of debate. These ques- over, positive cultures do not automatically confirm infection, and tions become particularly problematic with respect to ICU great discretion must be exercised in determining how the micro- patients, in whom SIRS is highly nonspecific. biologic information obtained should be used. For example, tracheal It would seem rational to take our current understanding of SIRS aspirates from intubated patients routinely reveal gram-negative flora, as encompassing both infectious and noninfectious pathology and but this finding in no way confirms pneumonia. A single blood cul- extrapolate it to the concept of source control. Indeed, as regards ture growing S. epidermidis is similarly difficult to interpret. more complex surgical patients, it may be appropriate to broaden Despite ubiquitous use in surgical patients, there is not a great the definition of source control to include control of all causes of deal of evidence in the clinical literature to substantiate the effec- SIRS, not merely infectious ones. For example, debriding devitalized tiveness of either empirical or streamlined antibiotic therapy. injured tissue, removing a rejected allograft, and resolving postoper- Further efforts must be made to find such evidence because this ative atelectasis are all important for successfully abating a systemic practice could theoretically exact a substantial cost from both the inflammatory state that might easily be mistaken for a manifestation patient and the environment in which the patient is cared for. In of infection. Deemphasizing infection as the predominant cause of the meantime, clinicians must approach the development of SIRS SIRS and withholding antibiotic therapy until stricter, more focused or other nonspecific signs of infection in their patients by predi- diagnostic criteria for infection are met should make treatment para- cating antimicrobial use on carefully formulated diagnostic crite- digms for managing difficult surgical patients, if not altogether more ria for the presence of infection; CDC consensus definitions of effective, at least more evaluable. infection are a good starting point. If one assumes that source control is in fact a therapeutic response to the presence of SIRS, one may then think of it as being either assisted or unassisted. The therapeutic response is initiated Source Control for Management of SIRS by the host, with either complete or partial success. Only in the lat- In the past, because the term sepsis was loosely used to describe ter instance should one assist the host’s efforts at source control by any general systemic inflammatory state and because such states providing antibiotics or taking surgical measures. This is by no often arose as a result of infection, it was assumed that antimicro- means to suggest that one should not search diligently for a cor- bial therapy was generally appropriate in the management of “sep- rectable cause of infection or inflammation but rather to suggest tic” patients. Now that sepsis has been redefined exclusively as that when such an effort yields negligible results, one should con- SIRS in a patient in whom a causative source of infection has been sider the possibility that SIRS may be not only appropriate but identified, it is clear that the use of antibiotics in “septic” (i.e., desirable and may represent the patient’s own adequate manage- SIRS) patients should be more discriminating. ment of the underlying physiologic insult. Thus, in certain situa- In the same vein, so-called source control was developed as a tions, source control may be best regarded as an endogenous or strategy for managing “septic” patients. Like the term sepsis, the unassisted event. For instance, when fever, tachycardia, and leuko- term source control traditionally connotes management of infec- cytosis are observed in a surgical patient who is coping well, antibi- tion rather than, more generally, management of a cause of inflam- otics should not necessarily be given automatically. Indeed, such mation. Classically, source control consists of a three-pronged “default therapy” should be actively discouraged. One should also approach employing measures to (1) eradicate a focus of infection, keep in mind that some forms of injury or insult (e.g., some viral (2) eliminate ongoing microbial contamination, and (3) render the infections) not only are very well managed without intervention but local environment inhospitable to microbial growth and tissue may not even prompt clinically evident SIRS. invasion. Diligent source control has long been considered pivotal The notion that no intervention may be required is under- to successful management of sepsis. Although this traditional standably difficult for many surgeons to embrace at the bedside. approach addresses the infectious causes of local or systemic Nonetheless, extensive ongoing research elucidating the complex inflammation very well in a great variety of clinical situations, good dynamic of circulating proinflammatory and counterinflammato- judgment must not yield to dogmatism in deciding which process- ry mediators (e.g., TNF, the interleukins, and a host of other es are required to control infection and inflammation. Challenging cytokines) suggests that a poorly understood but highly sophisti- convention, a surprising number of investigators have successfully cated biologic apparatus exists for responding to injury and insult. managed many supposedly surgical conditions (e.g., appendicitis22 Indeed, it is widely hypothesized (though yet unproved) that this and intra-abdominal abscess23) without intervention or by using systemic response can be manipulated to restore health in stressed only prolonged antibiotic therapy. Seasoned general surgeons are or deteriorating surgical patients. The prospect of untangling the well aware that if acute cholecystitis is not operated on urgently, it complex biology of systemic inflammation through advances in may certainly harm the patient or cause recurring discomfort, but this field is truly engaging. References 1. Marshall J, Sweeny D: Microbial infection and the 3. Goris RJA, Boekhorst TAP, Nuytinck JKS, et al: of sepsis. Crit Care Med 19:973, 1991 septic response in critical surgical illness. Arch Multiple organ failure: generalized autodestruc- 6. Sibbald WJ, Marshall J, Christou N, et al: “Sep- Surg 125:17, 1990 tive inflammation? Arch Surg 120:1109, 1985 sis”—clarity of existing terminology . . . or more 2. Meakins JL, Marshall JC:The gut as the motor of 4. Bone RC, Fisher CJ Jr, Clemmer TP, et al: Sepsis confusion? Crit Care Med 19:996, 1991 multiple system organ failure. Splanchnic syndrome: a valid clinical entity. Crit Care Med 7. American College of Chest Physicians/Society of Ischemia and Multiple Organ Failure. Marston A, 17: 389, 1989 Critical Care Medicine Consensus Conference: Ed. Edward Arnold, London, 1989, p 339 5. Bone RC: Let’s agree on terminology: definitions Definitions for sepsis and organ failure and guide-
  • 11. © 2003 WebMD Inc. All rights reserved. ACS Surgery: Principles and Practice 8 Critical Care 14 DIAGNOSIS OF INFECTION — 11 lines for the use of innovative therapies in sepsis. 13. Young B, Gleeson M, Cripps AW: C-reactive 19. American Thoracic Society: Hospital-acquired Crit Care Med 20:864, 1992 protein: a critical review. Pathology 23:118, 1991 pneumonia in adults: diagnosis, assessment of 8. Vincent J, Bihari DJ, Suter PM, et al: The preva- 14. Cursons RTM, Jeyerajah E, Sleigh JW: The use severity, initial antimicrobial therapy, and pre- lence of nosocomial infection in intensive care of polymerase chain reaction to detect sep- ventive strategies: a consensus statement. Am J units in Europe: results of the European ticemia in critically ill patients. Crit Care Med Respir Crit Care Med 153:1711, 1995 Prevalence of Infection in Intensive Care (EPIC) 27:937, 1999 20. Sterling TR, Ho EJ, Brehm WT, et al: Diag- Study. JAMA 274:639, 1995 15. The Society for Hospital Epidemiology of nosis and treatment of ventilator-associated pneu- 9. Casadevall A: Crisis in infectious diseases: time America, the Association for Practitioners in monia-impact on survival. Chest 110:1025, for a new paradigm? Clin Infect Dis 32:790, Infection Control, the Centers for Disease 1996 1996 Control, the Surgical Infection Society: Consensus paper on the surveillance of surgical 21. Timsit M, Misset B, Renaud B, et al: Effect of 10. Lennard ES, Mineshew BH, Dellinger EP, et al: previous antimicrobial therapy on the accuracy Leukocytosis at termination of antibiotherapy: wound infections. Infect Control Hosp Epide- miol 13:599, 1992 of the main procedures used to diagnose noso- its importance for intra-abdominal sepsis. Arch comial pneumonia in patients who are using Surg 115:918, 1980 16. Stamm WE, Hooton TM: Management of uri- mechanical ventilation. Chest 108:1036, 1997 11. Stone HH, Bourneuf AA, Stinson LD: Re- nary tract infection in adults. N Engl J Med liability of criteria for predicting recurrent sepsis. 329:1328, 1993 22. Eriksson S, Granstrom L: Randomized control- Arch Surg 120:17, 1985 17. Stark RP, Maki DG: Bacteriuria in the catheter- led trial of appendectomy versus antibiotic ther- ized patient: what quantitative level of bacteri- apy for acute appendicitis. Br J Surg 82:166, 12. Adnet F, Borron SW, Vicault E, et al: Value of C- 1995 reactive protein in the detection of bacterial con- uria is relevant? N Engl J Med 311:560, 1984 tamination at the time of presentation in drug- 18. Bullard KM, Dunn DL: Diagnosis and treat- 23. Montgomery RS, Wilson SE: Intraabdominal induced aspiration pneumonia. Chest 112:466, ment of bacteremia and intravascular catheter abscess: image-guided diagnosis and therapy. 1997 infections. Am J Surg 172(suppl 6A):13S, 1996 Clin Infect Dis 23:28, 1996