Risk Of Developing Infections Research Articles

Deap-seated infection and nonunion following internal fixation for Charcot foot deformity correction. A proportional meta-analysis of level 4 evidence

BackgroundGiven the paucity of literature on the management of infected metalwork and nonunion in neuropathic diabetic patients, a meta-analysis was designed to investigate the two major complications following Charcot reconstruction performed by means of internal fixation methods. MethodsWe searched PubMed, Scopus and CENTRAL until the 17th of May 2022 for completed studies investigating outcomes following midfoot and/or hindfoot and/or ankle diabetic Charcot reconstruction. For a paper to qualify for inclusion, an internal fixation element should have been considered. Random effects meta-analysis of proportion was performed to calculate the rate of post-operative deep-seated infections with the associated amputation rate and nonunions by using Open Meta-analyst software. Sub-analysis linked to anatomical location of reconstruction was performed and the quality of the included studies was appraised using the Moga tool. ResultsThirty studies with 492 eligible reconstructions were considered. Of those, deep-seated infections were diagnosed in 46 cases (Estimated proportion was 6.7%, 95% CI [4.2%–9.2%]). Debridement and antibiotic administration with or without metalwork removal were considered in the majority of the participants with successful clinical outcomes. Amputation was performed in 15 patients due to unmanageable post-operative infection and nonunion was reported in 17 studies (Estimated rates were 36.6%, 95% CI [18.4%–56.3%]; and 11.9%, 95%CI [6.6%–18.1%]; respectively). ConclusionsMeta-analysis showed that although the overall risk of infection development is less than 10%, just below one third of the infected cases undergo late amputation. Moreover, internal fixation reconstructions carry a nonunion risk of just above 10%.

Relationship between skeletal muscle index at the third lumbar vertebra with infection risk and long-term prognosis in patients with acute-on-chronic liver failure.

Infection is a major cause of increased mortality in patients with acute-on-chronic liver failure (ACLF). This study aims to examine the potential correlation of the skeletal muscle index at the third lumbar vertebra (L3-SMI) with infections among ACLF patients and to evaluate its impact on the long-term survival. This retrospective study included 126 patients who underwent abdominal computed tomography (CT) and were diagnosed with ACLF at our center between December 2017 and December 2021. L3-SMI was calculated using CT, and the clinical and biochemical data as well as MELD scores were also collected, so as to analyze the relationship between L3-SMI and infections in ACLF patients and the impact on long-term prognosis. Of the 126 ACLF patients enrolled, 50 had infections. In the multivariate logistic regression analysis, both L3-SMI [odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.81 - 0.97, P = 0.011] and hepatic encephalopathy (OR = 8.20, 95% CI = 1.70 - 39.59, P = 0.009) were independently associated with the risk of infection development. The overall survival (OS) estimates were obtained using Kaplan-Meier curves, and it was found that patients in the lowest tertile of L3-SMI had significantly lower 3-month, 6-month, 1-year, and 2-year survival rates than those in the highest tertile (P = 0.014; log-rank test). Low L3-SMI is an independent risk factor for the development of infections and significantly influences the long-term survival in ACLF patients.

151-OR: Social Determinants of Health Predict Diabetic Foot Infection Development

The objective was to identify social determinants of health (SDOH) associated with development of diabetic foot infection using the CDC Healthy People Framework at a tertiary care center. Targeted interrogation of structured and unstructured data using novel electronic medical record search engines was used to analyze patient encounters in individuals with diabetes and a concomitant diabetic foot complication during a twenty-year period (2001-2021). Among ~ 200 million encounters from people with diabetic foot complications, 8351 developed diabetic foot ulcers (DFU), and 1671 suffered a DFU infection. The risk of infection development in people with a DFU was assessed with the neighborhood disadvantaged index score from over 200 million separate patient encounters. The neighborhood disadvantaged index based on available geolocation data, provides a unitless value to describe the relative socioeconomic background of an individual as determined by the proportion (%) of non-Hispanic black, proportion (%) of female headed families with children, and the proportion of households (%) with public assistance income or food stamps in a defined area. The average disadvantaged index score for the DFU population was 0.06 and was comparable to the state of Michigan's average disadvantaged index of 0.05. In those persons who developed DFU infection, the index score averaged 0.13, 2.2x higher than the DFU population (p<0.05). Additionally, divorced individuals represented 2% of all individuals with DFU but accounted for 5% of those who developed DFU infection. This was disproportionate to other marriage statuses. These data strongly support the need to incorporate SDOH into updated DFU standard of care guidelines. Moreover, we clearly demonstrate that SDOH, more specifically geolocation data, can be used to identify individuals who are more likely to develop DFU infection. Thus, it is essential that SDOH are included in patient risk stratification to prevent severe diabetic foot complications. Disclosure B.M.Schmidt: None. A.Burant: None. N.Baker: None. A.Katona: None. C.Martin: Advisory Panel; Nevro Corp. C.M.Holmes: None. R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter & Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1K23DK131261-01A1, 5U01DK119083-05)

Active Surveillance Cultures and Procalcitonin in Combination With Clinical Data to Guide Empirical Antimicrobial Therapy in Hospitalized Medical Patients With Sepsis.

ObjectiveThe prevalence of colonization with multidrug-resistant organisms (MDRO) has increased over the last decade, reaching levels as high as 23% in certain patient populations. Active surveillance cultures (ASC) represent a valuable tool to identify patients colonized with MDRO to apply preventive measures, reduce transmission, and guide empiric antimicrobial therapy. There is a paucity of data evaluating the impact of admission ASCs to predict future infection. The aim of this study was to evaluate the concordance between ASCs results and the development of clinical infection by the same microorganism identified in the surveillance swab (“swab-related infection”), in hospitalized septic patients, and to evaluate the presence of specific risk factors associated with the development of a swab-related infection.MethodsAll adults admitted to the Diagnostic and Therapeutic Medicine Department of the University Hospital Campus Bio-Medico of Rome with a diagnosis of infection or any other medical reason with admission surveillance swabs (rectal or nasal) between January 2018 and February 2021 were included in the study. A retrospective chart review was conducted to identify patients that developed infections with concordant MDROs identified on ASC, and the risk factors for swab-related infection. Secondary outcomes were need of intensive care unit transfer, length of stay, sepsis or septic shock development, and all-cause mortality.ResultsA total of 528 patients were included in the study, of which 97 (18.3%) had a positive surveillance swab. Among patients with positive surveillance swabs, 18 (18.5%) developed an infection with the same microorganism recovered from the swab, 57 (58.8%) developed an infection with a different microorganism than that recovered from the surveillance swab, and 22 (22.7%) did not develop an infection during hospitalization. The number of colonized sites, an interventional procedure within the previous 3 months, a Systemic Inflammatory Response Syndrome (SIRS) score ≥ 2, and a quick Sequential Organ Failure Assessment (q-SOFA) score ≥ 2 were associated with a significantly higher risk of developing a swab-related infection. SIRS and q-SOFA scores ≥ 2 and procalcitonin ≥ 0.43 ng/ml help for identifying patients with a swab-related infection.ConclusionPatients with positive surveillance swabs were at increased risk for development of infections by the same MDRO identified in surveillance swabs (swab-related infection). This study is the first to show that the positivity of surveillance swabs, in combination with anamnestic data, PCT values, and SIRS or q-SOFA scores, serves as a valuable tool to help clinicians predict patients at higher risk for swab-related infection development and guide the administration of appropriate empiric antimicrobial therapy in septic patients.

Correlation Between Stress, Immunity and Intestinal Microbiota

Recent studies have shown the correlation between stress, immunity and intestinal microbiota. Chronic stress is associated with high production of inflammation mediators and risk of infection development, chronic systemic inflammation and inflammatory diseases development, as well as depressive disorders. Intestinal microbiota produces a wide range of compounds important for the organism: all major neurotransmitters, including serotonin, cytokines, tryptophan and short-chain fatty acids. Serotonin deficiency is considered as significant cause factor for development of anxiety, aggression, affective disorders and stress. Tryptophan is the serotonin precursor. Tryptophan is produced by intestinal microbiota or derived from food can be metabolized into kinurenine. Proinflammatory cytokines activate hypothalamus-pituitary-adrenal axis that increases of the level of circulating kinurenine and reduces the serotonin synthesis. Besides that, more kinurenine enters the brain during the inflammation process, and the neurotoxic pathway of kinurenine metabolism overwhelm the neuroprotective one. The less various microbiota microbiota is associated with increased response of the hypothalamus-pituitary-adrenal system, increase of pro-inflammatory cytokines, reduction of stress resistance, and depression. Enrichment of the diet with prebiotic components increases the diversity of the intestinal microbiota. Dietary interventions for intestinal microbiome also include probiotics promoting increased body resistance and cause less exposure to depression.

Chronic obstructive pulmonary disease and COVID-19

The coronavirus disease 2019 (COVID-19) pandemic tends to have a more severe clinical picture in the elderly and in patients with chronic diseases, one of which is chronic obstructive pulmonary disease (COPD). Around 2%–3% of patients infected with coronavirus have had the diagnosis of COPD; the critical care, intubation requirement, and mortality rate have been higher among this group of patients with the development of hypoxemia. Exacerbation and COVID-19 pneumonia are two differential diagnoses in patients with COPD; the fever among the symptoms, lymphopenia among the laboratory findings, and typical radiological findings in thoracic tomography of patients may be helpful in the diagnosis of COVID-19. The stabilization of the disease is important in the follow-up of patients with COPD during this pandemic; the continuation of maintenance treatment of patients has been accepted as the main strategy. Droplet and contact transmissions should be decreased, and basic hygiene and nutritional rules should be followed in the COPD patient group in which the risk of infection development is high. There are various opinions on the administration of treatment through nebulizers during the pandemic; the use of inhaler devices is the safer and recommended method. Since noninvasive mechanical ventilators may increase the risk of contamination, they are not included among the routine treatment recommendations for patients with COPD.

Soluble HLA-G pre-transplant levels to identify the risk for development of infection in heart transplant recipients

Infection is still a leading cause of death during the first year after heart transplantation. We evaluated the pre-transplant levels of HLA (Human Leukocyte antigen) – G molecules as a means of identifying heart recipients at risk of serious infections. We prospectively analyzed 122 adult heart transplant (HT) recipients. Serum samples were collected beforetransplantation and analyzed for sHLA-G levels by ELISA assay. The clinical follow-up period lasted 5 years. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 39 patients (32%) developed at least 1 serious bacterial infection. Higher pre-transplant sHLA-G levels were a risk factor for serious infection (above median value 5.4 ng/ml; relative risk 3.70; 95% confidence interval 1.03–12.64; p = 0.043). Patients with high levels of pre-transplant sHLA-G are also characterized by a lower overall survival at 5 years (p = 0.017), with microbial infections as major causes of death. No association was observed with the development rejection episode. Early monitoring of sHLA-G molecules proved useful for the identification of heart recipients who are at risk of serious infections.

Early Ultrasound Signs of Splenomegaly in Neonates

The purpose of the study is to determine early non-invasive (ultrasound) diagnostic criteria of splenomegaly in neonates with a high risk of congenital or postnatal infection.Materials and methods. In the prospective study, 163 newborn infants of the first week of live were included. All neonates included in the study were classified as possessing a high risk of an intra-uterine infection (IUI). Depending on the birth weight, the infants were split into two groups: group «А» — 80 full-term newborns with normal birth weight, and group «В» — 83 full-term newborns with fetal growth restriction (FGR). A comprehensive examination of newborns including spleen ultrasound was carried out.Results. An increased spleen weight coefficient (Km) was found in newborns with high risk of infection development that included congenital oromaxillofacial and gastrointestinal defects, perinatal contacts with various microorganism. The increased spleen weight and Km reflected conditions of the immune system organ of the newborn in response to an adverse exposure including infection.Conclusion. Ultrasound examination of morphometrical characteristics of the spleen in newborns with various medical conditions represents a convenient and simple method of early diagnosis of splenomegaly. The most sensitive index is the spleen weight coefficient (Km), which reflects the immune system organ response to an adverse perinatal exposure including contact with an infectious agent. The mean spleen weight coefficient is within the range of 1.1 to 3.0. When the index exceeds 4, the risk of development of an infectious disease increases. This method can be used as a screening approach for newborns of different gestation age who have been included in the high-risk group based on a congenital or early postnatal infection.

CORR Insights(®): Is Vancomycin-only Prophylaxis for Patients With Penicillin Allergy Associated With Increased Risk of Infection After Arthroplasty?

Where Are We Now? Deep prosthetic joint infections (PJI) following total joint arthroplasty (TJA) can be catastrophic. Timely administration of intravenous antibiotics prior to surgical incision is one of the most effective strategies to prevention of postoperative infections [6]. Currently, first- or second-generation cephalosporins are recommended for prophylaxis prior to routine THA and TKA [1]. However, in recent years, changes in patient demographics and increasing prevalence of resistant organisms in patients undergoing lower-extremity arthroplasty have raised the question of whether current recommendations are adequate. Combination therapies including the routine addition of vancomycin to the prophylactic antimicrobial regimen have shown only comparable efficacy to monotherapy in some studies, while increasing the risk of acute kidney injury in others [3, 8]. Furthermore, decolonization protocols have also been shown to be variable in terms of compliance and efficacy [10]. Therefore, the question remains: What is the correct approach to antibiotic prophylaxis prior to hip or knee replacement? In this article, Tan et al. present an interesting study on the use of vancomycin alone for prophylaxis in patients with penicillin allergies undergoing TJA. The authors found that administration of vancomycin alone did not increase the rate of deep surgical site infections, but decreased the risk for infections with Gram-positive organisms and antibiotic resistant organisms. Where Do We Need To Go? This work adds valuable information, but a number of questions remain. It would be important to validate these findings in other centers, and in prospective studies that permit tighter standardization of clinical practices. Of course, the endpoint we are most interested in—deep infection—requires much larger (and almost certainly multicenter) studies. The allure of widespread utilization of vancomycin as an effective agent to prevent infections with resistant organisms must be tempered by the potential risks, including renal toxicity, ototoxicity, and antimicrobial resistance. However, this is a common clinical scenario that not only affects arthroplasty surgeons, but all orthopaedic surgeons. Even though cross-reactivity and true anaphylaxis resulting from cephalosporin administration is only approximately 10% [2], most surgeons opt for antibiotic alternatives rather than “test-dosing” the patient under anesthesia to determine the presence or absence of true allergy. Vancomycin and clindamycin are commonly used alternatives in these situations, but concerns remain with regards to the efficacy of clindamycin and coverage of vancomycin as stand-alone agents [9]. Other studies have shown an increased risk of infections when only vancomycin is administered for routine prophylaxis [7]. Consequently, larger, prospective studies taking into account host factors, local antibiograms, and clinical practices such as decolonization protocols will be needed to definitively define the indications and efficacy for various antibiotic prophylactic protocols surrounding TJA. How Do We Get There? Many factors contribute to the risk of surgical site infections, and so to study the impact of antibiotics on infection properly, a multidisciplinary approach is called for. First, standardization of definitions and clinical practices will allow us to collaborate to find an answer to this problem without introducing confounding variables and bias. Today, there are established criteria for the work-up and diagnosis for infected TJA as well as clinical practice guidelines for the management of the infected TJA [5]. Second, a creation and contribution of surgical site infection and PJI data to various local and national registries will allow surveillance at a population level and the development of protocols based on specific antibiograms. Finally, and perhaps most challenging, is the need to define the “optimized” candidate for joint arthroplasty. Conditions such as diabetes, chronic kidney disease, obesity, and malnutrition have been shown to place patients at increased risk for development of infections postoperatively [4]. We need more studies that specifically ascertain at what point we should consider those sorts of conditions “well enough” managed that it is clinically reasonable to proceed with elective arthroplasty. Because of the increased risk, those studies also should help us to determine whether these higher-risk patients should be treated with different antibiotic approaches than low-risk patients? Identifying the correct antibiotic prophylaxis protocols can have profound and wide-reaching impact. The cost to prevent a single patient's infection must be counterbalanced against the risks in that patient of adverse effects, but also against societal costs, such as the development of antibiotic-resistant organisms. Orthopaedic surgeons, will be at the forefront of this dilemma and must play a part in practicing good, evidence-based, antibiotic stewardship.

Nasal colonization in children with community acquired methicillin-resistant Staphylococcus aureus.

Background:Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infections. The changing epidemiology of MRSA became evident in the 1990s when CA-MRSA cases were first reported. Nasal carriage of CA-MRSA is associated with an increased risk for development of infections in various populations.Materials and Methods:Anterior nares culture for the presence of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA was taken from 345 children attending kindergartens, who didn’t have any known risk factor for MRSA colonization. Also, children demographic variables were recorded. Identification of SA and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with standard microbiological test was performed. Finally, the susceptibility of isolated to various antibiotics determined. The data were analyzed with Whonet 5.6 software.Results:Of 345 children, 20 children (5.8%) were colonized with CA-MRSA, 86 children (24.9%) with MSSA and 239 cases (69.3%) didn’t have SA colonization. The highest rate of MSSA and MRSA colonization was obtained at the age of 6 years. The frequency distribution of SA (MSSA and MRSA) colonization prevalence didn’t have any significant differences based on age, gender and the admission time (P > 0.05); but it was significantly different in the urban areas (P < 0.001). The lowest resistance rate of CA-MRSA isolates, with a frequency of 10%, was detected with gentamicin, rifampin, and trimethoprim-sulfamethoxazole.Conclusions:In summary, CA-MRSA colonization was observed in child care centers remarkably. Therefore, by facing various infections due to SA especially in areas of low socio-economic status, it must be considered. Based on antibiogram test, empirical treatment with rifampin, gentamicin and ciprofloxacin is recommended during CA-MRSA infections.

Mesenchymal stromal cell implantation for stimulation of long bone healing aggravates Staphylococcus aureus induced osteomyelitis

Large bone defects requiring long-term osteosynthetic stabilization or repeated surgeries show a considerable rate of infection. Mesenchymal stromal cells (MSCs) have been successfully used to enhance bone regeneration, but their powerful immunomodulatory effects may impose an enhanced risk for osteomyelitis development. In order to unravel whether implantation of MSCs aggravates a simultaneous bone infection, a hydrogel-supported osteomyelitis ostectomy model was developed in which rats received a femoral bone defect with rigid plate-fixation. After fibrin-assisted transfer of Staphylococcus aureus (SA), effects of MSC implantation on osteomyelitis development were quantified over 3–4weeks.All SA-infected animals developed an acute local osteomyelitis with significantly increased blood neutrophil count, abscess formation and bone destruction. MSC-treatment of infected defects aggravated osteomyelitis according to a significantly elevated osteomyelitis score and enhanced distal bone loss with spongy alteration of cortical bone architecture. Increased attraction of macrophages, osteoclasts and regulation of pro- and anti-inflammatory mediators were potential MSC actions.Overall trophic actions of MSCs implanted into non-sterile bone defects may enhance an infection and/or exacerbate osteomyelitis. Studies on antibiotic carrier augmentation or antibiotic treatment are warranted to decide whether MSC implantation is a safe and promising therapy for orthopedic implant-stabilized bone defects at high risk for development of infection.

Risk factors for periprosthetic infection after reverse shoulder arthroplasty

Management of periprosthetic infection after reverse shoulder arthroplasty (RSA) remains a challenge. Whereas the infection rate after RSA has improved, more information would be helpful to identify patient risk factors for infection after RSA. The purpose of this study was to evaluate risk factors for infection after RSA. We identified 301 primary RSAs with a minimum of 1-year follow-up in a prospectively collected shoulder arthroplasty registry. We performed bivariate and multivariable logistic regression analyses to assess the association between patient demographic and clinical characteristics (age, sex, smoking, diabetes, rheumatoid arthritis, body mass index, and history of prior failed hemiarthroplasty or total shoulder arthroplasty) and periprosthetic infection after RSA. There were 15 periprosthetic infections after RSA (5.0%). Patients with a history of RSA for failed arthroplasty (odds ratio, 5.75; 95% confidence interval, 2.01-16.43; P = .001) and patients younger than 65 years had an increased risk for development of an infection (odds ratio, 4.0; 95% confidence interval, 1.21-15.35; P = .021). History of smoking, diabetes, rheumatoid arthritis, or obesity did not contribute to an increased risk of infection after RSA. This is the first study evaluating risk factors for infection after RSA while controlling for confounding variables with multivariable analysis. The greatest risk factors for infection after RSA were history of a prior failed arthroplasty and age younger than 65 years. Patients with these clinical characteristics should be counseled preoperatively about the increased risk for development of infection after RSA.

SAT0299 Rituximab Treatment of the Antisynthetase Syndrome

BackgroundAntisynthetase syndrome (ASS) is a severe variant of idiopathic inflammatory myopathies. Unfavorable prognosis of this disease is associated with interstitial lung disease (ILD). Conventional treatment with glucocorticoids (GC) and cytotoxic...

Chemical Chaperones Curcumin and 4-Phenylbutyric Acid Improve Secretion of Mutant Factor H R127H by Fibroblasts from a Factor H-Deficient Patient

Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. Patients with FH deficiency have a higher risk for development of infections and kidney diseases because of the uncontrolled activation and subsequent depletion of the central regulatory component C3 of the complement system. In this study, we investigated the consequences of the Arg(127)His mutation in FH (FH(R127H)) previously described in an FH-deficient patient, on the secretion of this protein by skin fibroblasts in vitro. We observed that, although the patient cells stimulated with IFN-γ were able to synthesize FH(R127H), the mutant protein was largely retained within the endoplasmic reticulum (ER), whereas normal human fibroblasts stimulated with IFN-γ secrete FH without retention in the ER. Moreover, the retention of FH(R127H) provoked enlargement of ER cisterns after treatment with IFN-γ. A similar ER retention was observed in Cos-7 cells expressing the mutant FH(R127H) protein. Despite this deficiency in secretion, we show that the FH(R127H) mutant is capable of functioning as a cofactor in the Factor I-mediated cleavage of C3. We then evaluated whether a treatment could increase the secretion of FH, and observed that the patient's fibroblasts treated with the chemical chaperones 4-phenylbutiric acid or curcumin increased the secretion rate of FH. We propose that these chemical chaperones could be used as alternative therapeutic agents to increase FH plasma levels in FH-deficient patients caused by secretion delay of this regulatory protein.

Clinicopathologic Characteristics and Endoscopic Treatment of Post-Traumatic Pancreatic Pseudocysts

Surgery is the treatment of choice for traumatic pseudocyst. Minimally invasive management of these collections has been used. The aim was to analyze the outcome after endoscopic treatment and the integrity of the main pancreatic duct caused by abdominal trauma. A total of 51 patients with traumatic pseudocyst who underwent endoscopic therapy were studied. All were symptomatic with a persistent collection for more than 6 weeks. Endoscopic retrograde pancreatography allowed characterization according to Takishima classification (1, 2, and 3), in which guided therapy was divided into transpapillary drainage (Takishima 2 and 3 without bulging), transmural (type 1), or combined (type 2 or 3 with bulging). Endoscopic retrograde pancreatography was obtained in 47 (90%) of 51 patients. Drainage was transmural in 13, combined in 24, and transpapillary in 10. The success and recurrence rates of endoscopic treatment were 94% and 8%, respectively. There were 9 complications but no procedure-related deaths. Patients with penetrating trauma had more recurrences (P = 0.01) and risk for development of infection (P = 0.045) than those with blunt trauma. Endoscopic treatment of traumatic pancreatic collection is safe and effective and can be considered a first-choice alternative to surgical treatment. Endoscopic retrograde pancreatography and Takishima classification are useful in determining the best endoscopic approach.

Families and the Sepsis Work-up: Considering their Fears

The neonatal patient is at significant risk for sepsis sometime during initial hospitalization in the Neonatal Intensive Care Unit (NICU). These risks include: an immature immune system; a skin barrier that is fragile and/or often penetrated to obtain needed lab testing or intravenous access; and poor nutritional status. Neonatal patients routinely require central venous access to provide long term nutrition and delivery of medications. Invasive lines as well as other foreign bodies like endotracheal tubes increase the incidence of sepsis in this population. 1 According to Kugelman, et al (2008) 2 the incidence of iatrogenic infections of the neonate during hospitalization is 18.2%. There is a significant inverse relationship between gestational age, birth weight and infection rates. That is with decreasing gestational ages and birth weights, preterm infants are at increased risk for development of infection. Infants who weigh less than 1000 grams and are 24 to 27 weeks gestation have an expected infection rate of 57% before hospital discharge. 3 Thus, sepsis is an issue of concern to both health

Humoral and cellular immune monitoring might be useful to identify liver transplant recipients at risk for development of infection

Orthotopic liver transplantation (OLT) is a successful therapy for patients with end-stage liver disease, and infection remains a significant cause of morbidity and mortality for patients undergoing this procedure. To assess humoral and cellular immunity markers as potential risk factors for development of infection, 46 consecutive liver transplant recipients (hepatitis C virus cirrhosis [n=17], alcoholic liver disease [n=15], hepatocellular carcinoma [n=9], autoimmune hepatitis [n=2], and other [n=3]) performed at a single center were prospectively studied. Maintenance therapy included tacrolimus (n=37) or cyclosporine (n=9) and prednisone. During follow-up, 27 patients had at least 1 episode of infection (58.7%). Pre-OLT immunoglobulin G (IgG) hypergammaglobulinemia (relative risk [RR] 2.78; 95% confidence interval [CI], 1.17-6.60, P=0.02), pre-OLT IgA hypergammaglobulinemia (RR 2.77, CI=1.24-6.19, P=0.012), and pre-OLT C3 hypocomplementemia (RR 3.02, CI=1.21-7.55, P=0.018) were associated with an increased risk for development of infection. Monitoring of Ig and complement levels might help to identify the risk of developing infection in OLT.

Immune Monitoring to Predict the Development of Infections After Immunosuppression for Solid Organ Transplantation and Autoimmune Diseases

Infections are relevant complications that cause morbidity in solid organ transplantation and autoimmune diseases. Infection represents a leading single cause of death in these patients. Identification of patients at risk for development of infections and specific intervention to decrease infection risk might lead to better outcomes, though one needs first to evaluate the presence of risk factors for infection. Underlying disease itself, activity of the disease, presence of co-morbidities, transplantation procedures along with immunosuppressive and immunomodulatory therapies may be associated with an increased risk of infections. Among host factors, there are no reliable immunological markers to predict infections. Immune monitoring (assessment of immunocompetence) to estimate the risk of infection has so far not been performed routinely, with the only exception of neutrophil counts, tuberculin skin testing and serological evaluation of donor and recipients of transplants for anti-cytomegalovirus IgG antibodies. However, alterations of specific and non specific humoral and cellular immunity may be associated with a higher risk of infection among immunosuppressed patients. We review studies that have been designed to assess immune monitoring for prediction of infections in patients with selected solid organ transplantations and systemic autoimmune diseases.

IgG monitoring to identify the risk for development of infection in heart transplant recipients

Infectious complication represents a significant source of morbidity and mortality in heart transplant recipients. To assess humoral immunity markers that can predict the development of infection, 38 consecutive recipients of heart transplants performed at a single center were prospectively studied. Induction therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood samples obtained before transplantation, and 7 days and 1 month after transplantation. During a mean follow-up of 16.9 months, 13 patients had at least one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV) infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1 patient had bacterial septicemia, 1 patient had urinary tract infection, and 1 patient had pulmonary nocardiosis. No significant association was found between infection and age, sex, immunosuppression, CMV serostatus of donor and recipient, or treated rejection episodes. Pre-transplant IgG (below median value=1140 mg/dL; relative risk [RR] 3.69; 95% confidence interval [CI] 1.01-13.54; P=0.04) and post-transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI 1.04-89.48; P=0.022) were associated with an increase in the risk for developing infections. Early monitoring of immunoglobulin levels might help to identify the risk for developing infection in heart transplantation.

Decreased Levels of Serum Immunoglobulins as a Risk Factor for Infection After Heart Transplantation

Objective We aimed to assess humoral immunity markers that provide prognostic value for the development of infections in heart transplant recipients. Patients and methods Forty-one heart transplant recipients underwent humoral immunity studies, including Immunoglobulin (IgG, IgA, IgM) and IgG subclasses determined by nephelometry on serum samples obtained before transplantation and 1 month after transplantation. Potential clinical risk factors were evaluated: waiting time for transplantation, pretransplant cytomegalovirus (CMV) serologic status of donor and recipient; recipient age; gender; cardiac disease severity before transplantation; type of immunosuppression; and occurrence of rejection. Outcome measures We measured infections requiring intravenous (IV) drug therapy during the first year. The association between variables and outcome was assessed using Cox proportional hazards modelling. Immunoglobulin levels were split into two groups using the median value observed as the cut-off. Results Of 41 patients studied, 19 (46%) had at least one episode of infection, 16 of which were CMV infections treated with IV gancyclovir, 1 CMV disease + aspergillosis and 2 bacterial pneumonia. Pretransplant IgG (<1055 mg/dL; RR 5.32; 95% confidence interval [CI] 1.73 to 16.29; P = .0034); pretransplant IgG1 (<695 mg/dL; RR 4.80; CI 1.57 to 14.68; P = .006), and posttransplant IgG levels (<589 mg/dL; RR 3.38; CI 1.21 to 9.44, P = .019) were associated with an increased risk of developing infections. Both waiting time for transplantation (RR 0.95; CI 0.91 to 0.98, P = .007) and pretransplant cardiac disease severity (RR 1.94; CI 1.17 to 3.21, P = .009) were significant risk factors for infection. After adjustment for clinical predictive variables, decreased values of posttransplant IgG remained significant predictors. Conclusions The existence of decreased levels of IgG in the setting of heart transplantation was associated with an higher risk for infection. Monitoring of immunoglobulin levels, a rapid and well-standardized nephelometric determination, in heart transplantation, may identify a subset of patients at risk for development of infections.