Pathogen Of Low Virulence Research Articles

Diagnostic Accuracy of Rotational Thromboelastometry for Low-Virulence Periprosthetic Joint Infections: A Pilot Study.

Periprosthetic joint infections (PJIs) are associated with altered coagulation dynamics; therefore, coagulation laboratory studies could be valuable for diagnosing PJI. This study aimed to evaluate the diagnostic role of Rotational Thromboelastometry (ROTEM) in detecting PJIs caused by low-virulence pathogens. A retrospective study was conducted, enrolling 78 patients who underwent exchange arthroplasty due to PJI due to high-virulence pathogens (Group A, n = 16), low-virulence pathogens (Group B, n = 20), or due to aseptic loosening (Group C, n = 20). Preoperative laboratory findings were compared among the three groups. Several ROTEM parameters differed in patients with PJIs caused by low-virulence pathogens, indicating a link between these infections and hypercoagulability. The development of low-virulence PJIs was associated with a higher maximum clot firmness (MCF) (Odds Ratio, 1.12; 95% Confidence Interval, 1.04-1.21; p = 0.001). Additionally, EXTEM MCF was found to have the highest diagnostic accuracy for these infections (Area Under the Curve, 0.841; sensitivity 90.0%; specificity 90.4%), surpassing that of C-reactive protein and the Erythrocyte Sedimentation Rate (p = 0.006 and p = 0.019, respectively). Our findings suggest that ROTEM analysis is a promising method for detecting the altered hemostatic dynamics associated with PJI caused by low-virulence pathogens.

FosA3 emerging in clinical carbapenemase-producing C. freundii.

Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C.freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii.

Sonication protocols and their contributions to the microbiological diagnosis of implant-associated infections: a review of the current scenario.

Addressing the existing problem in the microbiological diagnosis of infections associated with implants and the current debate about the real power of precision of sonicated fluid culture (SFC), the objective of this review is to describe the methodology and analyze and compare the results obtained in current studies on the subject. Furthermore, the present study also discusses and suggests the best parameters for performing sonication. A search was carried out for recent studies in the literature (2019-2023) that addressed this research topic. As a result, different sonication protocols were adopted in the studies analyzed, as expected, and consequently, there was significant variability between the results obtained regarding the sensitivity and specificity of the technique in relation to the traditional culture method (periprosthetic tissue culture - PTC). Coagulase-negative Staphylococcus (CoNS) and Staphylococcus aureus were identified as the main etiological agents by SFC and PTC, with SFC being important for the identification of pathogens of low virulence that are difficult to detect. Compared to chemical biofilm displacement methods, EDTA and DTT, SFC also produced variable results. In this context, this review provided an overview of the most current scenarios on the topic and theoretical support to improve sonication performance, especially with regard to sensitivity and specificity, by scoring the best parameters from various aspects, including sample collection, storage conditions, cultivation methods, microorganism identification techniques (both phenotypic and molecular) and the cutoff point for colony forming unit (CFU) counts. This study demonstrated the need for standardization of the technique and provided a theoretical basis for a sonication protocol that aims to achieve the highest levels of sensitivity and specificity for the reliable microbiological diagnosis of infections associated with implants and prosthetic devices, such as prosthetic joint infections (PJIs). However, practical application and additional complementary studies are still needed.

Stenotrophomonas maltophilia virulence: a current view.

Stenotrophomonas maltophilia is an opportunistic pathogen intrinsically resistant to multiple and broad-spectrum antibiotics. Although the bacterium is considered a low-virulence pathogen, it can cause various severe diseases and contributes significantly to the pathogenesis of multibacterial infections. During the COVID-19 pandemic, S. maltophilia has been recognized as one of the most common causative agents of respiratory co-infections and bacteremia in critically ill COVID-19 patients. The high ability to adapt to unfavorable environments and new habitat niches, as well as the sophisticated switching of metabolic pathways, are unique mechanisms that attract the attention of clinical researchers and experts studying the fundamental basis of virulence. In this review, we have summarized the current knowledge on the molecular aspects of S. maltophilia virulence and putative virulence factors, partially touched on interspecific bacterial interactions and iron uptake systems in the context of virulence, and have not addressed antibiotic resistance.

Can we rely on histopathological results for the diagnosis of prosthetic joint infection?

BackgroundHistopathology is one of the diagnostic criteria for prosthetic joint infection (PJI) proposed by all academic societies. The aim of this study was to compare histopathological and microbiological results from samples taken intraoperatively at the same site in patients with suspected or proven PJI. Patients and methodsWe conducted a monocenter retrospective study including all patients having undergone surgery from 2007 to 2015 with suspected or proven PJI. During surgery, both histopathological and microbiological samples were taken. Patients with a history of antimicrobial treatment 2 weeks prior to surgery were excluded. We considered as major criteria and gold standard for PJI diagnosis the presence of a sinus tract communication and/or the same microorganism in at least two cultures. ResultsFinally, 181 patients who underwent 309 surgeries were included. The median number of samples per surgery was 4 (interquartile range (IQR) = 3–5) for histopathology and 5 (IQR = 4–6) for microbiology. Major criteria were observed in 177 patients (57.3%), while positive histology in at least one intraoperative sample was present in 119 (38.5%). The concordance was 74%. The sensitivity and specificity of histopathology were 61% and 92% respectively. Available “histopathology-culture” sample pairs numbered 1247. Among them, positive histopathology was found in 292 samples (23%) and culture in 563 (45%). Concordance was 64%. The highest correlation was observed for very early infection (<1 month) (OR: 9.1, 95% CI: 3.6–23) and for virulent microorganisms, such as Staphylococcus aureus (OR: 7.8, 95% CI: 5.2–11.8), Streptococci (OR:7.8; 95% CI: 4–15.2) or Enterobacterales (OR: 7.4; 95% CI: 4.2–13.1). ConclusionHistopathologic examination is a valuable criterion for PJI diagnosis, but it may lack sensitivity for chronic infections or due to low-virulence pathogens.

Management and Clinical Outcome of Aortic Graft Infections: A Single-Center Retrospective Study.

This study aimed to evaluate the outcome of various treatment options for aortic graft infection (AGI) patients and identify factors affecting their prognosis. The data of AGI patients from January 2008 to December 2019 were retrospectively collected and analyzed. The primary endpoints were 30-day mortality and perioperative complication-related morbidity; the secondary endpoints were re-infection (RI) rates, primary and secondary graft patency, overall mortality, duration of antibiotic therapy, and the number of antibiotic types used in treatment. There was no significant difference in the 30-day mortality and perioperative-related complications between the conservative treatment, in-situ reconstruction (ISR), and extra-anatomic reconstruction (EAR) groups. The ISR group had lower re-infection rates and better overall survival rates than the EAR and conservative treatment groups. Different bypass graft conduits had no significant influence on the RI rate or primary and secondary graft patency. AGI patients infected with high-virulence pathogens had higher RI and overall mortality rates than those infected with low virulence pathogens, but this was not statistically significant. Initial procedures prior to the AGI also had no influence on the prognosis of AGI patients. Patients undergoing ISR or EAR surgery received antibiotic therapy for a longer duration than patients undergoing conservative treatment. Patients without RI received more types of antibiotics than patients with RI. ISR had lower RI rates and better overall survival rates than EAR and conservative treatment and may be a better choice for patients with AGI. Several factors were found to have no influence on patients' prognosis however, further studies are required.

Pseudomonas putida bacteremia in pediatric patients: A case series study

IntroductionBacteria of the genus Pseudomonas act as opportunistic pathogens. Pseudomonas putida has been considered a pathogen of low virulence and susceptible to multiple antibiotics, but in recent years resistant strains have emerged. The objective of this study is to describe the clinical characteristics, evolution and antibiotic resistance of P. putida bacteremia documented in pediatric hospitalized patients. MethodsRetrospective cases series. Pediatric patients admitted to the Prof. Dr. Juan P. Garrahan Hospital of Buenos Aires City, Argentina, with isolation in blood cultures of P. putida were included, between August 2015 and August 2020. ResultsSample consisting of 13 patients. Median age: 81 months (IQR 15−163). Ten of the patients were immunocompromised (77%), 11 (85%) had a central venous catheter, 2 (15%) received transfusions prior to the episode of bacteremia, and 6 (46%) had had an invasive procedure within the previous 30 days. Three patients (23%) presented bacteremia secondary to clinical focus and 10 (77%) had central venous catheter-associated bacteremia. All presented fever, 62% (8) evolved with sepsis and 15% (2) with septic shock. Two patients required admission to the intensive care unit (15%), and in 7 (54%) the central venous catheter was removed. None died. The median days of treatment was 14 (IQR 10−14). Resistance to carbapenems was 30%. ConclusionAll children had underlying comorbidities, most of them immunocompromised. Catheter-associated infection predominated. The sensitivity to antibiotics was variable. Given the emergence of multi-resistant strains, it is essential to know the local epidemiology.

Emergence of an epidemic hypervirulent clone of Enterobacter hormaechei coproducing mcr-9 and carbapenemases

Enterobacter cloacae complex (ECC) is an important nosocomial pathogen encompassing at least 22 species. Some of the species, such as E hormaechei and E asburiae, are clinically prevalent and frequently associated with a multidrug resistance phenotype.1 ECC is conventionally considered a low-virulence pathogen and often causes infections in immunocompromised patients, although interspecies diversities of pathogenicity have been noted in studies.2 A 2021 cohort study uncovered a hypervirulent species of ECC, E bugandensis, which was responsible for fatal septic shocks of newborn babies in a neonatal intensive care unit in France.

Polyphasic Analysis of Isolates from Kiwifruit Reveal New Genetic Lineages of Pseudomonas syringae pv. actinidifoliorum Look-Alike

Currently, kiwifruit cultivation arouses great economic interest in the agricultural sector in several countries of the European Union due to high consumer demand and good results achieved in terms of production potential and fruit quality. One of the main bacterial species that cause yield losses in kiwifruit plants is Pseudomonas syringae. Diseases such as bacterial canker, caused by pathovar (pv.) actinidiae; floral bud necrosis caused by pv. syringae and leaf spots caused by pv. actinidifoliorum (Pfm) are clear examples. Between 2014 and 2017, in the main kiwifruit producing areas in the north and east of Spain, several surveys were carried out in search of these pathogens. Analyses realized from symptomatic and asymptomatic plants of Actinidiadeliciosa revealed the existence of new bacterial isolates close to Pfm. These new isolates werelow virulence pathogens similar to Pfm but belonging to a new group of P. syringae that affected the leaves of A. chinensis var. deliciosa. This study focused on the characterization and classification of these new isolates by a polyphasic approach in order to provide more information for understanding how the different populations of P.syringae affecting kiwifruit. They had the phenotypic characteristics of Pfm but by molecular approaches, they constituted a supported genetic lineage closely-related to Pfm independent of the five lineages described so far. This work revealed the great diversity found in P. syringae species affecting kiwifruit plants and supports the hypothesis that Pfm is a low virulence pathogen which is long established in Europe.

The first case of Ochrobactrum intermedium bacteremia in a pediatric patient with malignant tumor

BackgroundOchrobactrum spp. are non-fermenting, Gram-negative bacilli that are regarded as emerging human pathogens of low virulence that can cause infections. The first identified case of Ochrobactrum intermedium was reported in 1998 in a liver transplantation patient with liver abcess. There are no reports of infections in pediatric patients. Here, we report the first case of O. intermedium bacteremia in a pediatric patient.Case presentationA two and a half years old male was admitted with fever, chills and nausea. He had been diagnosed as pineoblastoma and underwent surgical resection and chemotherapy. O. intermedium was isolated from his blood cultures and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), however, the Vitek II automated system failed to identify the organism. Then the pathogen was confirmed by 16S rDNA sequencing and average nucleotide identity result (ANI) confirmed the precise identification of O. intermedium at genomic level. In addition, the patient recovered well after antibiotic combined therapy.ConclusionsThis, to our knowledge, is the first case of O. intermedium bacteremia in a pediatric patient with malignant tumor. Traditional biochemical identification methods such as API 20NE or VITEK2 system cannot differentiate O. anthropi and O. intermedium. MALDI-TOF may be a promising tool for rapid identification of microorganisms such as O. intermedium.

Bacteriemia por Pseudomonas putida en niños: serie de casos

IntroductionBacteria of the genus Pseudomonas act as opportunistic pathogens. Pseudomonas putida has been considered a pathogen of low virulence and susceptible to multiple antibiotics, but in recent years resistant strains have emerged. The objective of this study is to describe the clinical characteristics, evolution and antibiotic resistance of P. putida bacteremia documented in pediatric hospitalized patients. MethodsRetrospective cases series. Pediatric patients admitted to the Prof. Dr. Juan P. Garrahan Hospital of Buenos Aires City, Argentina, with isolation in blood cultures of P. putida were included, between August 2015 and August 2020. ResultsSample consisting of 13 patients. Median age: 81 months (IQR 15-163). Ten of the patients were immunocompromised (77%), 11 (85%) had a central venous catheter, 2 (15%) received transfusions prior to the episode of bacteremia, and 6 (46%) had had an invasive procedure within the previous 30 days. Three patients (23%) presented bacteremia secondary to clinical focus and 10 (77%) had central venous catheter-associated bacteremia. All presented fever, 62% (8) evolved with sepsis and 15% (2) with septic shock. Two patients required admission to the intensive care unit (15%), and in 7 (54%) the central venous catheter was removed. None died. The median days of treatment was 14 (IQR 10-14). Resistance to carbapenems was 30%. ConclusionAll children had underlying comorbidities, most of them immunocompromised. Catheter-associated infection predominated. The sensitivity to antibiotics was variable. Given the emergence of multi-resistant strains, it is essential to know the local epidemiology.

Osteomyelitis caused by Aggregatibacter aphrophilus – a case report

Osteomyelitis in children is often secondary to haematogenous dissemination of bacteria into long bone metaphyses. Organisms causing osteomyelitis vary with age, and the virulence of different pathogens influences clinical presentation.1 Aetiological diagnosis is important in determining appropriate antibiotic therapy. This case involves an 11-year-old girl with 4 months worsening left knee pain and difficulty weight bearing. She had no fever, preceding trauma or recent dental procedures. Inflammatory markers were unremarkable, with radiological evidence of a Brodie’s abscess. She was trialled on oral cephalexin; despite transient clinical improvement, she re-presented with worsening symptoms. She was afebrile, with distal femoral point tenderness, no evidence of knee joint involvement and 1/6 mid-systolic murmur at the pulmonic area. Intravenous flucloxacillin was commenced, with debridement and washout of the distal femoral lesion. Surgical specimens grew Aggregetibacter aphrophilus sensitive to ampicillin, with negative blood cultures. Transthoracic echocardiography showed no valvular abnormalities. Her mobility improved, and she was transitioned to amoxicillin, with planned duration of 3 months. Aggregetibacter aphrophilus is a low virulence HACEK group bacterial pathogen with potential to cause osteomyelitis.2 This case of an uncommon, low-virulence pathogen causing osteomyelitis shows the importance of aetiological diagnosis to guide appropriate management, especially in cases with indolent presentations. 1.Arnold JC, Bradley JS. Osteoarticular infections in children. Infect Dis Clin North Am 2015; 29: 557–74.2.Norskov-Lauritsen N, Kilian M. Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description of Aggregatibacter aphrophilus to include V factor-dependent and V factor-independent isolates. Int J Syst Evolutionary Microbiol 2006; 56: 2135–46.

A Case Report of Methylobacterium radiotolerans Bacteremia and Brain Abscesses

Abstract Methylobacterium radiotolerans is a ubiquitous organism found in the environment and is considered an opportunistic pathogen of low virulence in humans. Most human infections from M. radiotolerans have been reported in immunocompromised hosts and have been reported mainly as bloodstream infections related to central venous catheters. We present the first known case of M. radiotolerans as a causative agent of multiple brain abscesses in an immunocompromised host.

Management of periprosthetic infection after reverse shoulder arthroplasty.

Periprosthetic shoulder infection (PSI) remains a devastating complication after reverse shoulder arthroplasty (RSA). Currently, scientific data related to the management of PSI are limited, and the optimal strategy and related clinical outcomes remain unclear. Guidelines from the Infectious Diseases Society of America for the management of periprosthetic joint infection are mainly based on data from patients after hip and knee arthroplasty. The aim of this study was to evaluate whether these guidelines are also valid for patients with PSI after RSA. In addition, the functional outcome according to the surgical intervention was assessed. An RSA database was retrospectively reviewed to identify infections after primary and revision RSAs, diagnosed between 2004 and 2018. Data collected included age, sex, indication for RSA, causative pathogen, surgical and antimicrobial treatment, functional outcome, and recurrence. Thirty-six patients with a PSI were identified. Surgical treatment was subdivided into débridement and implant retention (DAIR) (n = 6, 17%); 1-stage revision (n = 1, 3%); 2-stage revision (n = 16, 44%); multiple-stage revision (>2 stages) (n = 7, 19%); definitive spacer implantation (n = 2, 6%); and resection arthroplasty (n = 4, 11%). The most common causative pathogens were Staphylococcus epidermidis (n = 11, 31%) and Cutibacterium acnes (n = 9, 25%). Recurrence was diagnosed in 4 patients (11%), all of whom were initially treated with a DAIR approach. The median follow-up period was 36 months (range, 24-132 months). PSI is typically caused by low-virulence pathogens, which often are diagnosed with a delay, resulting in chronic infection at the time of surgery. Our results indicate that treatment of patients with chronic PSI with DAIR has a high recurrence rate. In addition, implant exchange (ie, 1- and 2-stage exchange) does not compromise the functional result as compared with implant retention. Thus, patients with chronic PSI should be treated with implant exchange. Future research should further clarify which surgical strategy (ie, 1-stage vs. 2-stage exchange) has a better outcome overall.

Phenotypic Modulation of Biofilm Formation in a Staphylococcus epidermidis Orthopedic Clinical Isolate Grown Under Different Mechanical Stimuli: Contribution From a Combined Proteomic Study.

One of the major causes of prosthetic joint failure is infection. Recently, coagulase negative Staphylococcus epidermidis has been identified as an emergent, nosocomial pathogen involved in subclinical prosthetic joint infections (PJIs). The diagnosis of PJIs mediated by S. epidermidis is usually complex and difficult due to the absence of acute clinical signs derived from the host immune system response. Therefore, analysis of protein patterns in biofilm-producing S. epidermidis allows for the examination of the molecular basis of biofilm formation. Thus, in the present study, the proteome of a clinical isolate S. epidermidis was analyzed when cultured in its planktonic or sessile form to examine protein expression changes depending on culture conditions. After 24 h of culture, sessile bacteria exhibited increased gene expression for ribosomal activity and for production of proteins related to the initial attachment phase, involved in the capsular polysaccharide/adhesin, surface associated proteins and peptidoglycan biosynthesis. Likewise, planktonic S. epidermidis was able to aggregate after 24 h, synthesizing the accumulation associate protein and cell-wall molecules through the activation of the YycFG and ArlRS, two component regulatory pathways. Prolonged culture under vigorous agitation generated a stressful growing environment triggering aggregation in a biofilm-like matrix as a mechanism to survive harsh conditions. Further studies will be essential to support these findings in order to further delineate the complex mechanisms of biofilm formation of S. epidermidis and they could provide the groundwork for the development of new drugs against biofilm-related infections, as well as the identification of novel biomarkers of subclinical or chronic infections mediated by these emerging, low virulence pathogens.

Low-grade-infections after spondylodeses-Achameleon? : Current findings and therapeutic strategies

Low-grade infections are caused by low-virulence pathogens. The course of these infections is often mild, which is why they are often delayed or not recognized at all. Chronic infections can lead to osteolysis and implant loosening. The rate of complications requiring revision, such as implant loosening or material failure, is known from the literature. However, the rate of low-grade infections in patients requiring spinal revision surgery remains unclear. The aim of this review is to present the latest treatment strategies for low-grade infections. The diagnostic and therapeutic options are summarized in the form of algorithms. The aim of this work is to raise an awareness of the possibility of alow-grade infection in patients undergoing spinal revision surgery. Review of the literature RESULTS: The detection of low-grade infections is difficult from both aclinical and aradiological point of view. In the event of unexplained implant loosening or failure despite the lack of local inflammatory signs and often normal laboratory parameters, alow-grade infection must be considered. Multiple microbiological sampling must be requested as part of the revision surgery. A histological examination is recommended for all revision surgery, especially if alow-grade infection is suspected. The diagnosis should ideally be completed by sonicating the implants with subsequent microbiological incubation of the preserved samples. If alow-grade infection is suspected, the biofilm-covered implant should be removed or replaced if instability/no fusion is present. The use of topical antibiotics could be useful, but its effectiveness in treating low-grade infections has not yet been sufficiently demonstrated. An algorithm for clinical decision-making in terms of diagnostic and therapeutic options is suggested.

Proteomic Analysis Reveals a Biofilm-Like Behavior of Planktonic Aggregates of Staphylococcus epidermidis Grown Under Environmental Pressure/Stress.

Prosthetic joint replacement failure has a huge impact on quality of life and hospitalization costs. A leading cause of prosthetic joint infection is bacteria-forming biofilm on the surface of orthopedic devices. Staphylococcus epidermidis is an emergent, low-virulence pathogen implicated in chronic infections, barely indistinguishable from aseptic loosening when embedded in a mature matrix. The literature on the behavior of quiescent S. epidermidis in mature biofilms is scarce. To fill this gap, we performed comparative analysis of the whole proteomic profiles of two methicillin-resistant S. epidermidis strains growing in planktonic and in sessile form to investigate the molecular mechanisms underlying biofilm stability. After 72-h culture of biofilm-forming S. epidermidis, overexpression of proteins involved in the synthesis of nucleoside triphosphate and polysaccharides was observed, whereas planktonic bacteria expressed proteins linked to stress and anaerobic growth. Cytological analysis was performed to determine why planktonic bacteria unexpectedly expressed proteins typical of sessile culture. Images evidenced that prolonged culture under vigorous agitation can create a stressful growing environment that triggers microorganism aggregation in a biofilm-like matrix as a mechanism to survive harsh conditions. The choice of a unique late time point provided an important clue for future investigations into the biofilm-like behavior of planktonic cells. Our preliminary results may inform comparative proteomic strategies in the study of mature bacterial biofilm. Finally, there is an increasing number of studies on the aggregation of free-floating bacteria embedded in an extracellular matrix, prompting the need to gain further insight into this mode of bacterial growth.

Periprosthetic joint infection: current concepts and outlook.

Periprosthetic joint infection (PJI) is a serious complication occurring in 1% to 2% of primary arthroplasties, which is associated with high morbidity and need for complex interdisciplinary treatment strategies.The challenge in the management of PJI is the persistence of micro-organisms on the implant surface in the form of biofilm. Understanding this ability, the phases of biofilm formation, antimicrobial susceptibility and the limitations of host local immune response allows an individual choice of the most suitable treatment.By using diagnostic methods for biofilm detection such as sonication, the sensitivity for diagnosing PJI is increasing, especially in chronic infections caused by low-virulence pathogens.The use of biofilm-active antibiotics enables eradication of micro-organisms in the presence of a foreign body. The total duration of antibiotic treatment following revision surgery should not exceed 12 weeks.Cite this article: EFORT Open Rev 2019;4:482-494. DOI: 10.1302/2058-5241.4.180092

Central Nervous System Opportunistic Infections.

Opportunistic infections of the central nervous system are classically associated with immunosuppression arising from infection with human immunodeficiency virus and with various hematologic malignancies. However, over the past few years, they are increasingly associated with transplantation and various immunosuppressive treatments used to treat autoimmune diseases. They cause significant morbidity and mortality and remain a diagnostic challenge due to the absence of typical signs and symptoms of infection and mimicry by various noninfectious causes. The pathogens associated with these infections are often commonly found pathogens of low virulence in immunocompetent hosts and include various bacteria, parasites, fungi, or viruses. These infections can present as various clinical syndromes, including meningitis, encephalitis, space-occupying lesions, stroke-like presentations, or even neoplastic manifestations. Progressive multifocal leukoencephalopathy can be seen in patients with multiple sclerosis on various new immunomodulatory drugs in addition to patients with human immunodeficiency virus, transplantation, or hematologic malignancies, and is characterized by multifocal white matter lesions. Human herpesvirus-6 causes severe encephalitis in transplant recipients, known as posttransplantation acute limbic encephalitis. Neoplastic manifestations like Epstein-Barr virus-associated primary central nervous system lymphoma and posttransplantation lymphoproliferative disorders are particularly challenging to diagnose and manage. Modern diagnostic techniques, including advanced imaging techniques like magnetic resonance spectroscopy, use of polymerase chain reaction, and metagenomic sequencing, can be helpful in early recognition of pathogens. Treatment of most of these involves lowering of immunosuppression when possible and use of specific antimicrobial agents when available. Improved outcomes can be seen when early diagnosis is made.

Serum C-reactive protein relationship in high- versus low-virulence pathogens in the diagnosis of periprosthetic joint infection.

Little is known about the relationship between the virulence of pathogens in periprosthetic joint infection (PJI) and C-reactive protein (CRP) levels. In this context, we assessed the performance of CRP for PJI. We collected the following data from 987 cases of total joint revision due to PJI and 386 cases of aseptic revision: age, gender, comorbidities, values for serum CRP, leukocytes, microbiology for preoperatively taken aspirations and at least 2 intraoperative biopsies, and presence or absence of a draining sinus. The mean CRP value in the PJI group was 50.2 mg l-1 (sd=62.2), while a lower CRP value of 11.6 mg l-1 (sd=25.3) was found in the control group. There were no significant differences for the CRP values between patients with and without draining sinus (P=0.4423). The difference in CRP between high-virulence and low-virulence micro-organisms was significant for both the hip and the knee (P<0.0001). For the hip, the area under the receiver operating characteristic curve (AUC) of CRP as a diagnostic marker for PJI was 0.830 and, for the knee, the AUC was 0.884. The optimal cutoff point for CRP as a diagnostic marker of PJI, calculated using Youden's index, was 8.90 mg l-1 for the hip and 9.99 mg l-1 for the knee. The study results add valuable new information regarding the organism profile that may help with the diagnostic workup and with the research and development of new strategies for diagnosing and treating PJI.