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Obesity and Infection Review Obesity and infection Matthew E Falagas, Maria Kompoti Lancet Infect Dis 2006; 6: Obesity increases morbidity and mortality through its multiple eff ects on nearly every human system. However, the 438–46 various aspects of the association between obesity and infection have not been reviewed. Thus, we reviewed the relevant Alfa Institute of Biomedical literature focusing on clinical aspects of this association. Obesity has a clear but not yet precisely defi ned eff ect on the Sciences (AIBS), Athens, Greece immune response through a variety of immune mediators, which leads to susceptibility to infections. Data on the (M E Falagas MD, M Kompoti MD); Department of Medicine, incidence and outcome of specifi c infections, especially community-acquired infections, in obese people are so far Tufts University School of limited. The available data suggest that obese people are more likely than people of normal weight to develop infections Medicine, Boston, MA, USA of various types including postoperative infections and other nosocomial infections, as well to develop serious (M E Falagas), and Department complications of common infections. Large prospective studies are required to further defi ne the burden of infectious of Medicine, Henry Dunant Hospital, Athens (M E Falagas) morbidity and mortality conferred by obesity. Correspondence to: Dr Matthew E Falagas, Alfa Introduction including obesity-related mechanisms that lead to Institute of Biomedical Sciences The US National Institutes of Health and the WHO classify predisposition to infections, the epidemiology of (AIBS), 9 Neapoleos Street, people regarding their body weight according to the body nosocomial and community-acquired infections in the 151 23 Marousi, Greece. Tel +30 (694) 611 0000; mass index (BMI), calculated as body weight (in kg) divided obese population, and special issues related to the fax +30 (210) 683 9605; by the body height (in m) squared. Overweight, obese, and management of infections in the obese patient. We briefl y [email protected] morbidly obese people are those with a BMI 25–30 kg/m², review infections that are the result of procedures for the 30–40 kg/m², and greater than 40 kg/m², respectively. management of obesity. In addition, we mention the Normal weight and underweight people are those with evidence for the reverse association between obesity and BMI 20–25 kg/m² and less than 20 kg/m², respectively. infection—namely, the possibility that infectious agents Obesity, through various well-described pathophysiological may have an aetiological role in obesity, an idea known as interactions, increases the risk of cardiovascular and other “infectobesity”. diseases, compromises the quality of life, and increases overall mortality.1,2 However, the various aspects of the Mechanisms that predispose obese patients to association between obesity and infection have not been infection reviewed. It has been recently recognised that the adipose tissue We review the available evidence regarding the various participates actively in infl ammation and immunity, aspects of the association between obesity and infection, producing and releasing a variety of proinfl ammatory and anti-infl ammatory factors, including the well-studied adipokines leptin and adiponectin, as well as cytokines Thymus and chemokines.3 Adiponectin is potently immuno- Protects thymocytes from 4 steroid-induced apoptosis suppressive, while leptin activates polymorphonuclear neutrophils,5 exerts proliferative and anti-apoptotic T cells activities on T lymphocytes, aff ects cytokine production, Regulates number and regulates the activation of monocytes/macrophages, and Obesity activation contributes to wound healing (fi gure).6 Leptin induction Increases interferon γ and inhibits interleukin 4 production seems to be a protective component of the immune Up-regulates the expression response and genetic leptin defi ciency in human beings Deficiency/resistance Regulates Modulates of adhesion molecules has been associated with increased mortality due to energy immune (VLA-2, ICAM-1) infections.7 The genetic defect of leptin-defi cient ob/ob homeostasis response mice, which causes a severe obese phenotype, is associated Macrophages with increased sensitivity to proinfl ammatory monocyte/ Modulates phagocytosis Inhibits macrophage-activating stimuli and impair ment of food and cytokine production 8 intake phagocytic functions, as well as reduced T-cell function. Leptin PMN cells These mutant mice are highly susceptible to bacterial Increases energy Regulates oxidative capacity infections with, for example, Listeria monocytogenes, consumption Klebsiella pneumoniae, etc.9,10 Monocytes Adipocytes participate in fatty acid composition and Induces release of TNFα, expression control of lipolysis. Prolonged, low-level immune and secretion of interleukin 1Ra stimulation induces hypertrophy of adipose tissue that partly emancipates the immune system from fl uctuations Figure: Leptin has a key role in linking nutritional state to the immune response in the abundance and composition of dietary lipids.11 Leptin regulates energy homeostasis by reducing food intake and increasing energy consumption and modulates the immune response to infl ammatory/infectious stimuli. Leptin defi ciency has been associated with susceptibility Increased susceptibility to infections in obese patients may to infections in animals as well as in human beings. PMN=polymorphonuclear, TNF=tumour necrosis factor. be related to decreased availability of arginine and 438 http://infection.thelancet.com Vol 6 July 2006 Review glutamine, resulting in decreased tumour necrosis factor adequate and trained staff . Risk of skin breakdown is (TNF)α production and increased nitric oxide release, as increased due to immobility caused by underlying disease, has been noted in obese rats.12 On the other hand, sepsis- improperly sized rooms and equipment, and inadequate related morbidity in obese patients may refl ect staff numbers or inadequately trained staff . Due to these microvascular infl ammation and thrombosis. In an diffi culties, obese patients may experience a prolonged experimental model, it was shown that obese mice length of stay, thus increasing their risk of acquiring a exhibited an exaggerated proinfl ammatory and thrombo- nosocomial infection.16–18 Most available data concern obese genic response to the same stimuli than their lean surgical patients and reveal a high incidence of clinically counterparts.13 relevant nosocomial infections such as pneumonia, wound In another animal model comparing the ability of obese infection, bacteraemia, and Clostridium diffi cile colitis.19 and lean Zucker rats to clear candida from the circulation and tissues, it was shown that 9 days after intravenous Surgical site infections injection of yeast suspension, obese rats carried a higher Surgical-site infections following various surgical burden of yeasts, residing particularly in the kidney.14 procedures are more common in obese compared with However, whether these fi ndings apply to human beings non-obese patients.20 Local changes, such as an increase remains to be studied. in adipose tissue, increase in local tissue trauma related The connection of proinfl ammatory states of obesity to retraction, lengthened operative time, and disturbance with the risk of infection has not been precisely determined, of body homeostatic balance, may contribute to the but leptin seems to have an important role in the immune increased incidence of surgical-site infections caused by response. Leptin defi ciency has been associated with obesity.21 Subcutaneous tissue oxygenation is reduced in susceptibility to infections in animals as well as in human obese patients and this may predispose to wound beings. More studies are needed in leptin-resistant obese infection, particularly after laparoscopic procedures.22 human beings. Additional research is needed to clarify Obesity was found to be independently associated with whether various interventions such as weight loss, exercise, Staphylococcus aureus nasal carriage, which is a risk or nutrient supplementation could help to ameliorate the factor for surgical-site infections.23 Obese women alterations in immunity of obese individuals.15 undergoing elective hysterectomy for benign conditions (dysfunctional bleeding or fi bromas) had an increased Obesity and clinical infections risk of surgical-site infections, particularly if no Nosocomial infections antimicrobial prophylaxis had been administered.24 The incidence of nosocomial infections in overweight and Morbid obesity was recognised as an independent risk obese patients is increased compared with normal weight factor for surgical-site infections after spinal surgery patients. Routine medical care of obese patients in everyday (laminectomy or spinal fusion).25,26 practice may present certain diffi culties. In some instances Obese patients, burdened with a high cardiovascular usual diagnostic and treatment procedures must be risk, frequently undergo cardiothoracic surgery. The modifi ed. For example, some computed tomography incidence of mediastinitis as well as of deep and super- equipment cannot accommodate obese patients above a fi cial sternal infection after coronary artery bypass certain weight limit. Routine care of non-ambulatory grafting is increased in obese compared with normal morbidly obese patients (eg, lifting and bathing) requires weight patients.27–29 In a large retrospective study of Reference Number of patients Comparison groups according to BMI (kg/m²) Type of infection Odds ratio
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