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Purpose: Pediatric osteoarticular infections (OAIs) are an orthopedic emergency that can lead to severe sequelae if not treated appropriately. Approximately half of the patients with OAIs in clinical practice fail to obtain microbiological results even after undergoing aspiration or surgery, which presents a significant challenge in clinical practice. The inability to identify pathogens can lead to incorrect antibiotic usage or under-treatment, increasing the risk of adverse outcomes. This study aims to investigate the clinical characteristics and prognosis of culture-negative OAIs compared to culture-positive OAIs through a meta-analysis, providing insights to optimize treatment strategies. Methods: A systematic search was conducted to identify cohort studies comparing the clinical characteristics and prognosis of children with culture-negative OAIs to those with culture-positive OAIs. The search encompassed the databases of Wanfang Data, China National Knowledge Infrastructure, China Biology Medicine disc, Excerpta Medica Database, PubMed and the Cochrane Library, with the literature review extending up to March 2024. Data were extracted from eligible articles and assessed using the Newcastle–Ottawa scale, and the articles were selected based on predefined inclusion and exclusion criteria. Results: Twelve literature reports covering 1630 patients were included in this meta-analysis. Publication bias did not significantly affect the results. The incidence of long-term sequelae, temperature before admission, baseline laboratory indicators and possibility of surgery in the culture-negative group of patients were significantly lower than those in the culture-positive group. In addition, there were no significant differences in gender, age, race, trauma history, patient delay, antibiotic usage before admission or clinical symptoms between the two groups. Conclusions: Children diagnosed with culture-negative OAIs generally demonstrated less severe systemic inflammatory responses, required shorter treatment durations, exhibited a reduced likelihood of requiring surgical intervention and were less prone to experience long-term functional impairments compared to children with culture-positive OAIs. However, no differences in patient characteristics and clinical symptoms were found between the two groups. Further large-scale studies are still required to validate these findings. Type of study: Meta-analysis. Level of evidence: Level III.

Kfir Lavi,1 Adi Klein,1,2 Noy Shtein,1 Vered Schichter Konfino,1,2 Vered Nir1,2 1Department of Pediatrics, Hillel Yaffe Medical Center, Hadera, Israel; 2Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, IsraelCorrespondence: Vered Nir, Hillel Yaffe Medical Center, Hadera, 38100, Israel, Tel +972-4-6304331, Fax +972-4-6304186, Email veredn@hymc.gov.ilIntroduction: Acute lobar nephronia (ALN) is a focal renal infection without liquefaction, historically regarded as rare in the pediatric population, yet recent literature suggests it may be under-diagnosed, which may result in the formation of renal abscess and future renal scarring.Methods: The clinical presentation, investigations, treatment and long-term outcomes of 5 patients diagnosed with ALN was described and literature review was conducted by reviewing publications in PubMed using the keywords “acute lobar nephronia” and “pediatric”.Results: Three patients were males, aged 1 to 11 years. The primary complaint in all cases was fever, accompanied by significantly elevated inflammatory markers. Upon presentation, none of the patients exhibited pyuria on urinalysis, and all had sterile blood and urine cultures. Diagnosis was based on CT scans for three patients and renal sonography for two. Main findings included hyperechogenic renal parenchyma, and hypodense localized parenchyma. Treatment consisted of broad-spectrum intravenous antibiotics, administered for 7 to 12 days and additional 1 week course with amoxicillin-clavulanate, resulting in similar defervescence times across all patients. None of the patients demonstrated recurrence and none had renal pathology upon repeated renal sonography and upon DMSA scintigraphy.Discussion: Clinical suspicion for ALN should arise in cases of abdominal pain and markedly increased inflammatory markers. It”s crucial to note that the absence of pyuria and negative culture results should not exclude ALN diagnosis, underscoring the need for a high index of suspicion in the pediatric population.Keywords: acute lobar nephronia, culture negative, urinary tract infection, pediatric

Infective endocarditis (IE) is associated with high morbidity and a mortality rate of 9-30% due to its life-threatening complications including systemic embolization of various organs. The complications are more common in culture-positive cases. In culture-negative IE, systemic embolism especially with multiorgan involvement occurring in a single patient is very rare. Such condition may significantly increase the hospital mortality and poses unique challenges in diagnosis and management. We present a case of a 14-year-old female who presented with a oneweek history of vague left upper quadrant pain and fever. She had a history of recurrent mild chest pain in the last one month but did not seek any treatment. She had no risk factors of IE. On presentation, she was fully conscious but with signs of septic shock requiring vasoconstrictor support and administration of a broad-spectrum antibiotics. There was loud pansystolic murmur on auscultation and generalised abdominal tenderness. Abdominal ultrasound showed geographic hypoechogenicity of the spleen with small bowel wall thickening. Contrast-enhanced computed tomography (CECT) abdomen confirmed splenic and renal infarction with ischaemic small bowel. Transthoracic echocardiography showed vegetation at the mitral valve. She developed a severe headache during admission. CT head and conventional cerebral angiography demonstrated a ruptured mycotic aneurysm. Her CRP and ESR were elevated. Anti-DNase B Titre was elevated raising suspicion of previous group A streptococcus infection. All her blood culture results were persistently negative throughout admission possibly due to the initiation of antibiotics prior to sample collection. Despite a negative culture, she developed disseminated embolism to various organs as described. The planned mitral valve surgery was delayed due to the intracranial bleed, and she underwent craniectomy for clot removal. Mitral valve replacement was performed one month later. During follow-up, she had good recovery with no signs of heart failure or significant impairment of quality of life. [ABSTRACT FROM AUTHOR]

Abstract Background The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. Methods Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. Results The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24–123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). Conclusion The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up.

This study aims to compare and analyze the clinical features, diagnosis, treatment and prognosis of culture-negative and culture-positive primary pyogenic spondylitis. In a retrospective analysis, 202 cases of adult primary pyogenic spondylitis with complete clinical data in our hospital from January 2013 to January 2020 were divided into two groups according to bacterial culture results: culture negative (n = 126) and culture positive (n = 76). We compare the clinical characteristics, diagnosis, treatment and prognosis of patients with different culture results. The culture positive rate was 37.62% (76/202). There were no significant differences in age, gender, affected segment, spinal abscess, diabetes mellitus, course of disease, surgery, recurrence, and follow-up time between the two groups (p>.05). There were statistically significant differences in hospital admission erythrocyte sedimentation rate (ESR), admission C-reactive protein (CRP), admission white blood cell (WBC) count, discharge ESR, discharge CRP, ESR decline rate, CRP (p<.05). There were statistically significant differences in the rate of decline, hospitalization days, and body temperature ≥38 °C (p<.05). Higher CRP levels on admission, antibiotic treatment time <6 weeks, and body temperature ≥ 38 °C are independent risk factors for infection recurrence. The culture-negative group's admission WBC, admission ESR, admission CRP, discharge ESR, discharge CRP, ESR decline rate, CRP decline rate, and hospital stay were lower than the culture positive group, the difference was statistically significant (p<.05). The independent risk factors for infection recurrence are higher CRP levels in hospital admission, antibiotic treatment time <6 weeks, and body temperature ≥ 38 °C. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of two-stage revision for culture-negative PJI remain controversial. This study analyzed outcomes after two-stage revision in patients with culture-negative and culture-positive periprosthetic joint infection (PJI) during follow-up lasting at least two years. Methods: Data were retrospectively analysed patients who underwent hip or knee revision arthroplasty from January 2008 to October 2020 at our medical center. The primary outcome was the re-revision rate, while secondary outcomes were the rates of reinfection, readmission, and mortality. Patients with culture-negative or culture-positive PJI were compared in terms of these outcomes, as well as survival time without reinfection or revision surgery, based on Kaplan‒Meier analysis. Results: The final analysis included 87 patients who were followed up for a mean of 72.3 months (range, 24–123 months). The mean age was 58.1 years in the culture-negative group (n = 24) and 59.1 years in the culture-positive group (n = 63). The two groups (culture-negative versus culture-positive) did not differ significantly in rates of re-revision (0.0% vs. 3.2%, p > 0.05), reinfection (4.2% vs. 3.2%, p > 0.05), readmission (8.4% vs. 8.0%, p > 0.05), or mortality (8.3% vs. 7.9%, p > 0.05). They were also similar in survival rates without infection-related complications or revision surgery at 100 months (91.5% in the culture-negative group vs. 87.9% in the culture-positive group; Mantel‒Cox log-rank χ2 = 0.251, p = 0.616). Conclusion: The two-stage revision proves to be a well-tolerated and effective procedure in both culture-negative and culture-positive PJI during mid to long-term follow-up. [ABSTRACT FROM AUTHOR]

Pseudopropionibacterium propionicum (P.p.) is an anaerobic, Gram-positive, branching beaded rod that is a component of the human microbiome. An infection of the thoracic cavity with P.p. can mimic tuberculosis (TB), nocardiosis, and malignancy. We present a case of a 77-year-old male who presented with dyspnea and a productive cough who was initially misdiagnosed with TB based on positive acid-fast staining of a pleural biopsy specimen and an elevated adenosine deaminase level of the pleural fluid. He was then diagnosed with nocardiosis based on the Gram stain of his pleural fluid that showed a Gram-positive beaded and branching rod. The pleural fluid specimen was culture-negative, but the diagnosis of thoracic P.p. infection was determined with next-generation sequencing (NGS). The patient was initially treated with imipenem and minocycline, then ceftriaxone and minocycline, and later changed to minocycline only. This report shows the utility of NGS in making a microbiological diagnosis when other techniques either failed to provide a result (culture) or gave misleading information (histopathologic exam, pleural fluid adenosine deaminase determination, and organism morphology on Gram stain). [ABSTRACT FROM AUTHOR]

Abstract Purpose The aim of this study was to compare the clinical outcomes of culture-negative periprosthetic joint infection (CN PJI) with those of culture-positive periprosthetic joint infection (CP PJI). Methods Data were obtained from Embase, Web of Science and EBSCO for all available studies comparing the clinical outcomes of CN PJI with those of CP PJI. The quality of the studies was scored using the Newcastle–Ottawa scale (NOS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess clinical outcomes. Subgroup analyses were performed to explain heterogeneity among the included studies. Publication bias was estimated using Begg’s funnel plot. Sensitivity analysis was performed to test the stability of pooled results. Results Thirty studies with 1630 (38.7%) CN PJI and 2577 (61.3%) CP PJI were included in this meta-analysis. The pooled results of the included studies showed that overall failure rate in CN PJI group (19.0%, 309/1630) was significantly lower than that in CP PJI group (23.4%, 604/2577) (OR 0.63, 95% CI 0.47–0.84, P = 0.002). We performed the subgroup analysis based on the surgical strategies, the pooled results of nine studies for patients undergoing debridement, antibiotics and implant retention (DAIR) revealed that failure rate in CN PJI group (22.2%, 53/239) was significantly lower than that in CP PJI group (29.3%, 227/775) (OR 0.62, 95% CI 0.43–0.90, P = 0.01), the pooled results of four studies for patients undergoing one-stage revision revealed that failure rate between CN PJI group (11.5%, 11/96) and CP PJI group (7.6%, 27/355) had no significant difference (OR 1.57, 95% CI 0.75–3.26, P = 0.23), and the pooled results of 19 studies for patients undergoing two-stage revision revealed that failure rate in CN PJI group (16.1%, 171/1062) was significantly lower than that in CP PJI group (20.4%, 206/1010) (OR 0.52, 95% CI 0.34–0.79, P = 0.002). Conclusions CN PJI group had similar or better survival rate when compared with CP PJI group for patients who underwent DAIR, one-stage or two-stage revision. Negative culture was not a worse prognostic factor for PJI.

Yao Liu,1– 3 Jinqing Liu,1– 3 Lei Fu,1– 3 Chuan Jiang,1– 3 Shifang Peng1– 3 1Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Viral Hepatitis of Hunan Province, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Shifang Peng, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Email sfp1988@csu.edu.cnObjective: Despite its high case-fatality risk, pyogenic liver abscess (PLA) lacks clear management guidelines in patients with negative microbial cultures. Our aim was to evaluate differences in clinical characteristics between patients with culture-negative liver abscess (CNLA) and those with culture-positive liver abscess (CPLA), and identify differences in the main causative pathogen.Methods: In this study, we retrospectively collected medical records of PLA patients admitted to a teaching hospital from January 2010 to December 2019.Results: In total, 324 PLA patients were enrolled in this study. Of these, 202 (62.3%) cases were confirmed cultural positive, including 109 patients (54%) and 20 (9.9%) patients infected with Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E.coli), respectively. Patients in the CPLA group were older (p=0.029) and had higher prevalence of abscesses larger than 5 cm in diameter (p = 0.003), gas-forming rate (p = 0.016), and percutaneous drainage (p < 0.001) compared with CNLA group. Patients with CPLA had significantly longer hospitalizations than those with CNLA (p = 0.010). Nevertheless, there was no significant difference in in-hospital mortality between the two groups (p = 0.415). Compared with patients with E. coli, those with K. pneumoniae had higher incidence of diabetes mellitus (p = 0.041), solitary abscess (p < 0.001), localization in the right hepatic lobe (p = 0.033), abscess size larger than 5 cm (p < 0.001) and percutaneous drainage (p = 0.002), but mortality was not significantly different (p = 1.000).Conclusion: No significant difference in in-hospital mortality was found between patients with CNLA and those with CPLA group. However, clinical characteristics and management were different between the main causative pathogens, including K. pneumoniae and E. coli.Keywords: PLA, culture negative, culture positive, Klebsiella pneumoniae, Escherichia coli

Introduction: Culture-positive peritoneal dialysis (PD)-related peritonitis depends on proper sample collection and culture technique. Patients are investigated for fungal and tubercular peritonitis once the initial peritoneal effluent grows no bacteria and the patient is unresponsive to antimicrobials. However, they are diagnosed late in the course of illness and lead to irreversible peritoneal damage preventing reinsertion of PD catheter. The aim of the study was to assess the role of polymerase chain reaction (PCR) in diagnosis of fungal and Mycobacterium tuberculosis (MTB)-related peritonitis in patients on PD who presented with features of peritonitis. Materials and Methods: This was a prospective study and included patients who were diagnosed to have PD-related peritonitis as per the International Society of PD guidelines. All patients underwent panfungal and MTB complex (MTC) PCR of PD effluent on day 1 of admission. Results: Eighty-five patients with PD-related peritonitis were included in the study. In patients with no bacterial growth on PD fluid, panfungal PCR was positive in 22 (25.8%) patients and 2 (2.4%) patients had positive MTC PCR. Fungal organism could be isolated in 10 (11.7%) patients. Nine percent of patients with fungal peritonitis died. Conclusion: The use of PCR in patients with PD-related peritonitis will help in early diagnosis and management of fungal and tubercular peritonitis. It will also help in reducing mortality in these patients.

Background The optimal duration for antibiotics in patients hospitalized with culture-negative serious infection (CNSI) is unknown. We compared outcomes in patients with CNSI treated with 3 or 4 vs ≥5 days of antibiotics. Methods CNSI was identified among adults admitted to 111 US hospitals between 2009 and 2014 via electronic health record data, defined as suspected serious infection (blood cultures drawn and ≥3 days of antibiotics) and negative culture- and nonculture-based tests for infection. Patients treated with antibiotics on their last hospital day and patients with diagnosis codes for sepsis-mimicking conditions were excluded. Among patients without fevers/hypothermia or vasopressors by day 3, we calculated odds ratios for in-hospital mortality or discharge to hospice associated with 3 or 4 vs ≥5 days of antibiotics, adjusting for confounders. Results Antibiotics were discontinued in 3 or 4 days in 1862 (9%) of 20 714 patients with CNSI. Early discontinuation was not associated with higher mortality odds overall (adjusted odds ratio [aOR], 1.27; 95% CI,.98–1.65), in patients presenting with (1.39;.88–2.22) and without sepsis (1.17;.81–1.69), and in those with pulmonary (1.23;.65–2.34) and nonpulmonary CNSI (1.30;.99–1.72). Early discontinuation appeared detrimental with propensity score weighting (aOR, 1.36; 95% CI, 1.03–1.80) and when retaining patients with sepsis mimics (1.38; 1.16–1.65), but it was protective (0.48;.37–.64]) when retaining patients who received antibiotics on their last hospital day. Conclusions Early discontinuation of antibiotics in CNSI was not associated with significant harm in our primary analysis, but different conclusions based on alternative analytic decisions, as well as risk of residual confounding, indicate that randomized controlled trials are needed. [ABSTRACT FROM AUTHOR]

Background: A preoperative pathogen detection is considered a prerequisite before undergoing one-stage exchange for prosthetic joint infection (PJI) according to most guidelines. This study compares patients with and without preoperative pathogen detection undergoing one-stage exchange for PJI of the hip. The authors put up the hypothesis that a preoperative pathogen detection is no prerequisite in selected cases undergoing one-stage exchange. Methods: 30 consecutive patients with PJI of the hip, treated with one-stage exchange, between 2011 and 2021, were retrospectively included. Mean age was 70 years and mean follow-up 2.1 ± 1.8 years. PJI was defined according to the European Bone and Joint Infection Society. One-stage exchange was performed in (1) chronic PJI longer than 4 weeks, (2) well-retained bone condition, (3) absence of multiple prior revisions for PJI (≤ 2) with absence of difficult-to-treat pathogens in the past, and (4) necessity/preference for early mobility due to comorbidities/age. Results: One-stage exchange was performed in 20 patients with and in 10 without a preoperative pathogen detection. Age (71 years, 68 years, p = 0.519), sex (50% and 30% males, p = 0.440), American Society of Anesthesiologists Score (2.2, 2.4, p = 0.502), and Charlson Comorbidity Index (3, 4, p = 0.530) did not differ among the two groups. No significant differences were noted concerning preoperative CRP (15 mg/l, 43 mg/l, p = 0.228), synovial cell count (15.990/nl, 5.308/nl, p = 0.887), radiological signs of loosening (55%, 50%, p = 0.999), and intraoperative histopathology. Except a higher rate of coagulase-negative staphylococci (70%, 20%, p = 0.019) in patients with a preoperative pathogen detection, no significant differences in pathogen spectrum were identified among groups. Revision for PJI recurrence was performed in one patient with an initial preoperative pathogen detection (3.3%). Additional revisions were performed for dislocation in two and postoperative hematoma in one patient. Revision rate for both septic and aseptic causes (p = 0.999), stay in hospital (16 and 15 days, p = 0.373) and modified Harris Hip Score (60, 71, p = 0.350) did not differ between groups. Conclusion: Patients with and without a preoperative pathogen detection did not show significant differences concerning baseline characteristics, clinical and functional outcomes at 2 years. An absent preoperative pathogen detection is no absolute contraindication for one-stage exchange in chronic PJI, if involving good bone quality and absence of multiple prior revisions. [ABSTRACT FROM AUTHOR]

Pseudopropionibacterium propionicum (P.p.) is an anaerobic, Gram-positive, branching beaded rod that is a component of the human microbiome. An infection of the thoracic cavity with P.p. can mimic tuberculosis (TB), nocardiosis, and malignancy. We present a case of a 77-year-old male who presented with dyspnea and a productive cough who was initially misdiagnosed with TB based on positive acid-fast staining of a pleural biopsy specimen and an elevated adenosine deaminase level of the pleural fluid. He was then diagnosed with nocardiosis based on the Gram stain of his pleural fluid that showed a Gram-positive beaded and branching rod. The pleural fluid specimen was culture-negative, but the diagnosis of thoracic P.p. infection was determined with next-generation sequencing (NGS). The patient was initially treated with imipenem and minocycline, then ceftriaxone and minocycline, and later changed to minocycline only. This report shows the utility of NGS in making a microbiological diagnosis when other techniques either failed to provide a result (culture) or gave misleading information (histopathologic exam, pleural fluid adenosine deaminase determination, and organism morphology on Gram stain).

Purpose: The aim of this study was to compare the clinical outcomes of culture-negative periprosthetic joint infection (CN PJI) with those of culture-positive periprosthetic joint infection (CP PJI). Methods: Data were obtained from Embase, Web of Science and EBSCO for all available studies comparing the clinical outcomes of CN PJI with those of CP PJI. The quality of the studies was scored using the Newcastle–Ottawa scale (NOS). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess clinical outcomes. Subgroup analyses were performed to explain heterogeneity among the included studies. Publication bias was estimated using Begg's funnel plot. Sensitivity analysis was performed to test the stability of pooled results. Results: Thirty studies with 1630 (38.7%) CN PJI and 2577 (61.3%) CP PJI were included in this meta-analysis. The pooled results of the included studies showed that overall failure rate in CN PJI group (19.0%, 309/1630) was significantly lower than that in CP PJI group (23.4%, 604/2577) (OR 0.63, 95% CI 0.47–0.84, P = 0.002). We performed the subgroup analysis based on the surgical strategies, the pooled results of nine studies for patients undergoing debridement, antibiotics and implant retention (DAIR) revealed that failure rate in CN PJI group (22.2%, 53/239) was significantly lower than that in CP PJI group (29.3%, 227/775) (OR 0.62, 95% CI 0.43–0.90, P = 0.01), the pooled results of four studies for patients undergoing one-stage revision revealed that failure rate between CN PJI group (11.5%, 11/96) and CP PJI group (7.6%, 27/355) had no significant difference (OR 1.57, 95% CI 0.75–3.26, P = 0.23), and the pooled results of 19 studies for patients undergoing two-stage revision revealed that failure rate in CN PJI group (16.1%, 171/1062) was significantly lower than that in CP PJI group (20.4%, 206/1010) (OR 0.52, 95% CI 0.34–0.79, P = 0.002). Conclusions: CN PJI group had similar or better survival rate when compared with CP PJI group for patients who underwent DAIR, one-stage or two-stage revision. Negative culture was not a worse prognostic factor for PJI. [ABSTRACT FROM AUTHOR]

Purpose: The main requirement for performing the one-stage septic exchange is the pre-operative identification of the pathogen and its susceptibility. The purpose of this study is to evaluate the success rate with special focus on reinfection in a cohort of patients who underwent one-stage septic knee or hip revision for pre-operative culture-negative PJI. Methods: We retrospectively analyzed 640 patients treated by one-stage revision for chronic knee or hip PJI between January 1, 2016, and December 31, 2018. Only cases with pre-operative culture-negative PJI, with culture-negative synovial aspirations and one negative open biopsy, were analyzed. We evaluated the septic and aseptic complication and the rate of complication-free survival defined as the time from the date of first operation and the date of complication events. Results: A total of 22 patients fulfilled the inclusion and were enrolled. The mean age of the group was 73.2 ± 9.8 years, with a median ASA score of 3 (range 3–4). After mean follow-up of 3.6 ± 2.6 years, 86.4% (19 out of 22) of patients reported no complications. Two patients (9.1%) after one-stage hip required revision arthroplasty due to septic failure, while one patient (4.5%) with one-stage knee had revision for femoral component aseptic loosening. Conclusion: Our analysis suggests that the absence of pre-operative pathogen detection may not be contraindication to the one-stage revision in selected patients. The one-stage exchange might be considered in patients with pre-operative negative cultures in presence of ASA > 3 and multiple comorbidities that are not able to tolerate multiple surgeries. [ABSTRACT FROM AUTHOR]

Introduction: Fracture-related infection (FRI) represents a challenging clinical scenario. Limited evidence exists regarding treatment failure after initial management of FRI. The objective of our investigation was to determine incidence and risk factors for treatment failure in FRI. Materials and methods: We conducted a retrospective review of patients treated for FRI between 2011 and 2015 at three level 1 trauma centers. One hundred and thirty-four patients treated for FRI were identified. Demographic and clinical variables were extracted from the medical record. Treatment failure was defined as the need for repeat debridement or surgical revision seven or more days after the presumed final procedure for infection treatment. Univariate comparisons were conducted between patients who experienced treatment failure and those who did not. Multivariable logistic regression was conducted to identify independent associations with treatment failure. Results: Of the 134 FRI patients, 51 (38.1%) experienced treatment failure. Patients who failed were more likely to have had an open injury (31% versus 17%; p = 0.05), to have undergone implant removal (p = 0.03), and additional index I&D procedures (3.3 versus 1.6; p < 0.001). Most culture results identified a single organism (62%), while 15% were culture negative. Treatment failure was more common in culture-negative infections (p = 0.08). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common organism associated with treatment failure (29%; p = 0.08). Multivariate regression demonstrated a statistically significant association between treatment failure and two or more irrigation and debridement (I&D) procedures (OR 13.22, 95% CI 4.77–36.62, p < 0.001) and culture-negative infection (OR 4.74, 95% CI 1.26–17.83, p = 0.02). Conclusions: The rate of treatment failure following FRI continues to be high. Important risk factors associated with treatment failure include open fracture, implant removal, and multiple I&D procedures. While MRSA remains common, culture-negative infection represents a novel risk factor for failure, suggesting aggressive treatment of clinically diagnosed cases remains critical even without positive culture data. Level of evidence: Retrospective cohort study; Level III. [ABSTRACT FROM AUTHOR]

Introduction: Different approaches have been proposed for bacterial identification in patients with a suspected periprosthetic joint infection (PJI). If a one-stage procedure is considered, a higher rate of preoperative bacterial identification can be achieved if biopsy is included in the diagnostic work-up. The performance of open biopsy (OB) in the context of PJI has not been clearly determined yet. The purpose of this study was to determine the value of an OB added to two consecutive culture-negative joint aspirations during PJI workup. Materials and methods: We retrospectively analyzed the OB data from a single institution. Patients under PJI work-up of the hip or knee with two culture-negative periprosthetic aspirations who underwent OB were included. Sensitivity and specificity were calculated using the musculoskeletal infection society (MSIS) criteria as gold standard. Patients undergoing urgent irrigation and debridement and patients with history of surgery to the affected joint in the prior 6 weeks were excluded. Results: 126 patients were included in this study. 62 (49.2%) patients had prior revisions, 48 of them due to PJI. The sensitivity and specificity of OB was 69.4% and 89.1%, respectively. The OB procedure led to the identification of the causative germ in 50 out of 126 (40%) cases so they could undergo one-stage (septic) exchange. Conclusion: The OB is a valuable resource if preoperative synovial fluid cultures are negative, a high suspicion of infection persists and a one-stage procedure is preferred. It intends bacteria identification and allows surgeons to evaluate prosthetic complications for further surgical procedures. [ABSTRACT FROM AUTHOR]

Objective To compare the clinical outcomes of culture‐negative periprosthetic joint infection (CN PJI) with those of culture‐positive periprosthetic joint infection (CP PJI). Methods This study retrospectively examined data from 77 patients who underwent revision surgery due to periprosthetic joint infection (PJI) after hip and knee arthroplasty at our center from January 2012 to June 2017. There were 37 males and 40 females, with an average age of 63.6 year. All patients were classified by Tsukayama type, according to the bacterial culture results of synovial fluid and pre‐ and intraoperative tissues, 24 cases were included in the CN PJI group, and 53 cases were included in the CP PJI group. All patients underwent routine blood tests, liver, renal function tests, erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) measurements. The remission rates of CN PJI and CP PJI were compared. The effects of the culture results on the curative effect were further compared by survival analysis. Results The patients were followed regularly with an average of 29.2 months (range, 12–76 months). In total, there were 24 cases of CN PJI, with an incidence of 29.63%. The overall success rate of CN PJI group was 86.4% (19/22), and overall success rate of CP PJI group was 87.5% (42/48). The relative efficacy of various surgical options was: one‐stage revision 100% (7/7), two‐stage revision 96.3% (26/27), debridement and implant retention 64.3% (9/14), respectively. There was no significant difference in the success rate between the CN PJI group and the CP PJI group. The incidence of antibiotic‐related complications for the CN PJI group was significantly higher than that of the CP PJI group, with 58.3% for CN PJI and 11.3% for CP PJI, respectively. Conclusion When CN PJI was treated according to the strict standards for the diagnosis and treatment, the success rate of treatment for the CN PJI group was similar to that for the CP PJI group. The incidence of antibiotic‐related complications from the CN PJI group was higher than that from the CP PJI group.

BACKGROUND: Periprosthetic joint infection, a serious complication after artificial joint arthroplasty, has always been a thorny problem in clinical practice. At present, the research on the characteristics of the pathogenic bacteria is insufficient, and more research is needed to help clinical diagnosis and treatment. OBJECTIVE: To explore the distribution and drug resistance of pathogens in periprosthetic joint infection after knee and hip arthroplasties, and to compare the characteristics of different pathogen culture results. METHODS: A retrospective single-center research was used to study the data of 102 cases of periprosthetic joint infection in the Department of Orthopedics, First Affiliated Hospital of Zhengzhou University from September 2013 to September 2020. Pathogen culture results, drug resistance, and other diagnosis and treatment information were collected. According to the results of pathogen culture, the patients were divided into four groups: gram-positive bacteria, gramnegative bacteria, fungi, and negative culture. The differences in general condition, clinical features, operation methods, and infection control were compared among the four groups. RESULTS AND CONCLUSION: (1) Totally 66 of 102 patients with periprosthetic joint infection were cultured positive for pathogenic bacteria, and 71 strains of pathogenic bacteria were detected. Gram-positive bacteria accounted for 57.8%. Staphylococcus epidermidis (21.1%) and Staphylococcus aureus (15.5%) were the most common. Gram-negative bacteria accounted for 29.6% and Escherichia coli (12.7%) was the most common. Fungi accounted for 12.7%, with Candida parapsilosis (5.6%) being the most common. (2) Gram-positive bacteria had high resistance rates to penicillin G, oxacillin, clindamycin, and erythromycin, and 0% to vancomycin, tigecycline, and linezolid. Gram-negative bacteria had a high resistance rate to antibiotics such as quinolones, gentamicin, ampicillin, and cefazolin; no drug-resistant fungi had been found. (3) There was no significant difference in sex, age, basic disease, operation site, infection type, sinus, operation mode, and infection control rate among the four groups (P > 0.05). In early infection, the C reactive protein in culture negative group was lower than that in gram-positive bacteria group (P < 0.05), and red serum sedimentation rate and white blood cell count in culture negative group were significantly lower than those in gram-negative bacteria group (P < 0.05). Leukocyte, C-reactive protein, and erythrocyte sedimentation rate of hip periprosthetic infection were higher than those of knee periprosthetic infection (P < 0.05). (4) It is concluded that the main pathogen causing periprosthetic joint infection is still gram-positive bacteria, of which Staphylococcus accounts for the largest proportion. The increase of Candida parapsilosis infection is worthy of attention. Multiple pathogenic bacteria have a high drug resistance rate to some conventional antibiotics, so the use of antibiotics should be adjusted in time according to the results of drug susceptibility and efficacy. [ABSTRACT FROM AUTHOR]

Cryptococcal meningitis is a leading cause of morbidity and mortality in patients infected with human immunodeficiency virus. In over 90% of cases, it occurs at CD4 T lymphocyte (CD4) cell counts of less than 100 cells/mm 3 . Cryptococcomas are rare granulomatous lesions that can occur in disseminated central nervous system cryptococcal infection, primarily in immunocompetent hosts. Here we report a case of disseminated cryptococcal meningitis with numerous cryptococcomas mimicking metastases in a patient with HIV and a CD4 count of 115. The patient's serum and cerebrospinal fluid (CSF) cryptococcal antigen, CSF cryptococcal polymerase chain reaction, and serum and CSF cryptococcal cultures were all negative. Brain biopsy pathology confirmed the diagnosis. In this paper, we highlight the importance of early cerebral biopsy in the diagnosis and management of cryptococcoma., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background : Significant proportion of congenital heart surgery (CHS) children exhibit sepsis, but have negative blood culture and defined “culture negative sepsis (CNS).” Aims and Objectives : Retrospective analysis of CNS patients undergoing CHS. Material and Methods : 437 consecutive CHS children grouped as controls (antibiotic prophylaxis), CNS, and culture positive sepsis (CPS). Results : Incidences of CNS and CPS were 16% and 7%. Median mechanical ventilation (MV) in hours among CPS, CNS, and control was 116 (45–271), 63 (23–112), and 18 (6–28) (P < 0.001), respectively. Multivariable linear regression identified CPS (median ratio: 3.1 [2.3–4.1], P < 0.001), CNS (median ratio: 5.6 [3.7–8.4], P < 0.001), and weight (kg) (median ratio: 0.98 [0.96–0.99], P = 0.009) as associations of MV. Intensive care unit (ICU) stay (hours) was 192 (120–288) in CNS, 288 (156–444) in CPS, and 72 (48–120) in controls (P < 0.0001). Multivariable linear regression showed CNS (median ratio: 2.4 [2.0–2.9], P< 0.001) CPS (median ratio: 3.3 [2.5–4.4], P < 0.001), and weight (median ratio: 0.98 [0.97–0.99], P = 0.001) prolonging ICU stay. Mortality was 10.7%, 2.9% and 1.2% in CPS, CNS, and control (P = 0.03). Multivariable regression identified CPS an independent predictor of mortality with odds ratio 8.6 (1.7–44.9; P = 0.010). 11.26% patients in CNS and 79.3% in CPS received antibiotics for more than 10 d ays. Conclusion : Incidence of CNS was 16%; duration of MV and ICU stay and mortality was significantly less in CNS than CPS patients.

In this review we present the background of a study of cases with negative cultures, where the patients had symptoms of lower urinary tract infections, by overviewing the significance of urine culture results and the urinary microbiome. In the late 19th century, once a pure culture technique had been established, the method was applied to the diagnosis of urinary tract infections. The concept of significant bacteriuria, with 105 CFU/ml as the diagnostic threshold for acute pyelonephritis, was then introduced to provide a means of differentiating between contamination from the microbial community at the external genitalia in the urine specimen and true infection. Later, 102 CFU/ml was considered to be diagnostic for lower urinary tract infections, but around 104 CFU/ml was generally utilized as the threshold because of practical applicability. On the other hand, 20-40% of the patients with typical acute-cystitis symptoms and pyuria have been reported to have negative cultures. Although previous studies suggested that the phenomenon was mainly due to unculturable Escherichia coli detected by quantitative PCR, the true etiology remains unclear. The application of enhanced urine culture and next-generation sequencing techniques has identified a resident microbial community within the urinary tract, known as the the urinary microbiome, and has led to rejection of the dogma that“urine is normally sterile.” The contribution of the urinary microbiome not only to urinary tract infections but also to urgent urinary incontinence, painful bladder syndrome and genitourinary cancer has been investigated. [ABSTRACT FROM AUTHOR]

Background : Significant proportion of congenital heart surgery (CHS) children exhibit sepsis, but have negative blood culture and defined "culture negative sepsis (CNS)." Aims and Objectives : Retrospective analysis of CNS patients undergoing CHS. Material and Methods : 437 consecutive CHS children grouped as controls (antibiotic prophylaxis), CNS, and culture positive sepsis (CPS). Results : Incidences of CNS and CPS were 16% and 7%. Median mechanical ventilation (MV) in hours among CPS, CNS, and control was 116 (45--271), 63 (23--112), and 18 (6--28) (P < 0.001), respectively. Multivariable linear regression identified CPS (median ratio: 3.1 [2.3--4.1], P < 0.001), CNS (median ratio: 5.6 [3.7--8.4], P < 0.001), and weight (kg) (median ratio: 0.98 [0.96--0.99], P = 0.009) as associations of MV. Intensive care unit (ICU) stay (hours) was 192 (120--288) in CNS, 288 (156--444) in CPS, and 72 (48--120) in controls (P < 0.0001). Multivariable linear regression showed CNS (median ratio: 2.4 [2.0--2.9], P< 0.001) CPS (median ratio: 3.3 [2.5--4.4], P < 0.001), and weight (median ratio: 0.98 [0.97--0.99], P ≤ 0.001) prolonging ICU stay. Mortality was 10.7%, 2.9% and 1.2% in CPS, CNS, and control (P = 0.03). Multivariable regression identified CPS an independent predictor of mortality with odds ratio 8.6 (1.7--44.9; P = 0.010). 11.26% patients in CNS and 79.3% in CPS received antibiotics for more than 10 days. Conclusion : Incidence of CNS was 16%; duration of MV and ICU stay and mortality was significantly less in CNS than CPS patients. [ABSTRACT FROM AUTHOR]

Identification of the causative organism(s) in periprosthetic joint infection (PJI) is a challenging task. The shortcomings of traditional cultures have been emphasized in recent literature, culminating in a clinical entity known as "culture-negative PJI." Amidst the growing burden of biofilm infections that are inherently difficult to culture, the field of clinical microbiology has seen a paradigm shift from culture-based to molecular-based methods. These novel techniques hold much promise in the demystification of culture-negative PJI and revolutionization of the microbiology laboratory. This article outlines the clinical implications of culture-negative PJI, common causes of this diagnostic conundrum, established strategies to improve culture yield, and newer molecular techniques to detect infectious organisms. [ABSTRACT FROM AUTHOR]

BackgroundWe assessed the outcomes and characteristics of culture-negative septic shock (CNSS) and culture-positive septic shock (CPSS) in pediatric intensive care unit (PICU).MethodsWe performed a retrospective study on the data of children admitted to the PICU due to septic shock between January 2018 and December 2021. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay (LOS) of hospital, the need for mechanical ventilation (MV) and continue renal replacement therapy (CRRT).ResultsOverall, 238 patients were enrolled. 114 patients (47.9%) had positive cultures (60 blood samples, 41 sputum samples, 17 pus samples, and 19 others), 18 of whom were cultured positive at two sites, 1 at three sites, and 3 had two different types of bacteria at same site. The in-hospital mortality was 47.1%. There were no significant differences in the in-hospital mortality (47.6% vs. 46.5%, P = 0.866), PRISM-III score (10 vs. 12, P = 0.409), PIM-3 score (0.08 vs. 0.07, P = 0.845), pSOFA score (10 vs. 10, P = 0.677) or the need for MV (64.5% vs. 68.4%, P = 0.524) and CRRT (29.8% vs. 34.2%, P = 0.470) between the CNSS group and the CPSS group. The Procalcitonin (8.89 ng/ml vs. 28.39 ng/ml, P = 0.001) and C-reactive protein (28 mg/L vs. 58 mg/L, P = 0.001) levels were significantly lower in the CNSS group than in the CPSS group, while WBC count (9.03 × 109/L vs. 5.02 × 109/L, P = 0.002) and serum sodium (137 mmol/L vs. 132 mmol/L, P = 0.001) was significantly higher in CNSS. The LOS of hospital was significantly longer (16 days vs. 11 days, P = 0.011) in the CPSS group than in the CNSS group, while the LOS of PICU (5 days vs. 4 days, P = 0.094) stay was not significantly different.ConclusionCompared with children with CNSS, children with CPSS had higher PCT and CRP levels, but lower WBC count. Children with CPSS had longer LOS of hospital. However, positive or negative culture results were not associated with in-hospital mortality, the LOS of PICU, the need for MV or CRRT in children with septic shock.

Despite its limitations, a culture remains the "gold standard" for pathogen identification in patients who have periprosthetic joint infection (PJI). Recently, a synovial fluid antigen test has been introduced by a commercial entity. The purpose of this multicenter study was to determine the accuracy of the antigen test in the diagnosis of PJI. This retrospective study identified 613 patients undergoing revision total knee arthroplasty who had undergone preoperative synovial fluid analysis. A PJI was defined using the 2018 International Consensus Meeting (ICM) criteria. Patients who had an extended period (> 180 days) from aspiration to revision procedure (n = 62), those presenting within 90 days of their index arthroplasty procedure (n = 17), and patients who had an inconclusive ICM score (n = 8) were excluded. Using receiver operator characteristic curve analyses, we examined the utility of the microbial identification (MID) antigen test and any positive culture (either preoperative or intraoperative) in the diagnosis of PJI. A total of 526 patients were included. Of these, 125 (23.8%) were ICM positive and 401 (76.2%) were ICM negative. Culture demonstrated an area under the curve (AUC) of 0.864, sensitivity of 75.2%, and specificity of 97.5%. On the other hand, the MID test exhibited an AUC of 0.802, sensitivity of 61.6%, and specificity of 98.8%. The AUC of culture was significantly higher than that of the MID test (P =.037). The MID test was positive in 41.9% of culture-negative PJI cases. We also observed a high rate of discordance (29.7%) when both culture and the MID test were positive in the ICM-positive group. Synovial fluid antigen testing does not provide additional clinical benefit when compared to traditional cultures for the diagnosis of PJI. The antigen test had low sensitivity in the diagnosis of PJI and a relatively high rate of discordance with culture. Level III. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical outcomes of culture‐negative periprosthetic joint infection (CN PJI) with those of culture‐positive periprosthetic joint infection (CP PJI). Methods: This study retrospectively examined data from 77 patients who underwent revision surgery due to periprosthetic joint infection (PJI) after hip and knee arthroplasty at our center from January 2012 to June 2017. There were 37 males and 40 females, with an average age of 63.6 year. All patients were classified by Tsukayama type, according to the bacterial culture results of synovial fluid and pre‐ and intraoperative tissues, 24 cases were included in the CN PJI group, and 53 cases were included in the CP PJI group. All patients underwent routine blood tests, liver, renal function tests, erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) measurements. The remission rates of CN PJI and CP PJI were compared. The effects of the culture results on the curative effect were further compared by survival analysis. Results: The patients were followed regularly with an average of 29.2 months (range, 12–76 months). In total, there were 24 cases of CN PJI, with an incidence of 29.63%. The overall success rate of CN PJI group was 86.4% (19/22), and overall success rate of CP PJI group was 87.5% (42/48). The relative efficacy of various surgical options was: one‐stage revision 100% (7/7), two‐stage revision 96.3% (26/27), debridement and implant retention 64.3% (9/14), respectively. There was no significant difference in the success rate between the CN PJI group and the CP PJI group. The incidence of antibiotic‐related complications for the CN PJI group was significantly higher than that of the CP PJI group, with 58.3% for CN PJI and 11.3% for CP PJI, respectively. Conclusion: When CN PJI was treated according to the strict standards for the diagnosis and treatment, the success rate of treatment for the CN PJI group was similar to that for the CP PJI group. The incidence of antibiotic‐related complications from the CN PJI group was higher than that from the CP PJI group. [ABSTRACT FROM AUTHOR]

Introduction: An increase in the number of primary total joint arthroplasties has correspondingly led to an increase in revisions as a result of various complications. The prosthetic joint infection (PJI) is a major complication with concordantly increased morbidity and costs. Through this study, we aimed to determine the bacteriological profiles of PJI diagnosed at our institute and analyze them in the context of patient profiles, joints affected, and the center where the index procedure was done. Materials and Methods: A retrospective study of the revision surgeries for PJI in hip and knee arthroplasties during the period between 2014 and 2019 was conducted. An analysis of 43 patient profiles, with 29 of those being knees and the rest 14 being hips was done, concerning the clinical picture, microbiological profile, and co-morbidities. Results: PJI constituted 31.03% of the revision cases. The knee joint was involved in 67.44% (n = 29) and the hip joint in 32.56% (n = 14). Early infection was seen in 2 (4.65%) and late infections in the remaining 41 (95.34%). 51.66% (n = 22) were culture-positive PJI, whereas 48.34% (n = 21) were culture-negative (CN) PJI. Preoperative C-reactive protein was elevated in 46.51% of the patients (48.27% knees and 42.87% hips). The erythrocyte sedimentation rate was preoperatively elevated by 65.12%. Of the comorbidities PJI was associated with, diabetes mellitus in 30.23%, hypertension in 39.53%, hypothyroidism in 16.28%, skin disorders in 4.65% (psoriasis and eczema), and immunosuppression in 4.65% cases. Conclusions: Microbial growth on routine culture is not mandatorily positive in several clinically suspected PJI. Hence, a stringent protocol requires to be followed in the use of antibiotics, the collection and transportation of samples, and in the selection of media for cultures in the cases of PJI. Notwithstanding the limitations of this study, we conclude that bacterial infections do not follow any predictable patterns, and constant vigilance with a low threshold to suspect and investigate PJI is needed in the management of PJI. We propose based on our study findings that no antibiotics should be used only after a bacteriological diagnosis and antibiotic sensitivity is obtained, else it results in a high rate of CN PJIs.

Aucun germe n'est identifié dans près de 20 % des arthrites septiques (AS). Certaines études montrent que les AS avec ou sans germe identifié sont identiques et doivent être traitées de la même façon alors que d'autres suggèrent que si les caractéristiques cliniques sont identiques, le pronostic des AS sans germe est meilleur et que ce groupe est contaminé par des arthrites non septiques. L'absence de germe identifié peut être due à une antibiothérapie préalable, à un germe fragile difficile à cultiver ou au fait que l'arthrite n'est pas septique. Les arthrites microcristallines sont la cause la plus fréquente d'arthrite aiguë mais elles peuvent favoriser une AS. Polyarthrite rhumatoïde et spondyloarthrite sont les causes les plus fréquentes d'arthrite pseudo-septique mais beaucoup d'autres étiologies rares sont possibles. Il n'existe aucun moyen fiable pour différencier arthrite septique et non septique quand les recherches bactériologiques sont négatives. La qualité de l'enquête bactériologique avant toute antibiothérapie reste le meilleur moyen de limiter la fréquence des AS sans germe identifié. No germ can be identified in nearly 20% of clinically suspected septic arthritis (SA). Some studies show that SA with and without germ identified are the same and should be treated in the same way while others suggest that if the clinical features are the same, the prognosis of SA without an identified germ is better and patients can be given alternative diagnoses. Culture-negative SA may be due to prior antibiotic therapy, a fastidious or non-cultivable bacteria on usual media, or to the fact that the arthritis is not septic. Crystal arthritis is the most common cause of acute arthritis, but it can coexist with SA. Rheumatoid arthritis and spondyloarthritis are the most common causes of pseudoseptic arthritis, but many other rare causes are possible. There is no reliable way to differentiate septic and non-septic arthritis when bacteriological finding is negative. The quality of the bacteriological investigation before any antibiotic therapy remains the best way to limit the frequency of SA without germ identified. [ABSTRACT FROM AUTHOR]

Background: Endophthalmitis is a potentially blinding intraocular infection following intraocular surgery or trauma. Prompt diagnosis and treatment are important in preventing devastating visual complications. Procalcitonin (PCT) is a promising biomarker for diagnosing bacterial infections. The aim of the study was to measure vitreous PCT in infectious endophthalmitis and assess its utility as a biomarker. Methods: In this prospective study, vitreous was collected from patients with non-infectious retinal disorders and infectious endophthalmitis. PCT was measured using the Human Procalcitonin ELISA Kit. The diagnostic performance of PCT was calculated via receiver operating characteristic curves. Results: The study included three groups: patients with non-infectious retinal conditions, culture-positive endophthalmitis, and culture-negative endophthalmitis. The average PCT was 75.74 ± 26.8 pg mL−1, 100.24 ± 12.9 pg mL−1, and 126.41 ± 26.47 pg mL−1 in control, culture-negative, and culture-positive endophthalmitis, respectively. There was a significant difference in the vitreous PCT in the study and control groups (p = 0.04), but not between culture-positive and culture-negative endophthalmitis (p = 0.65). The sensitivity (66.7%) and specificity (65%) for PCT with a cut-off of ≤ 54.88 pg mL−1(p = 0.31) implied that its diagnostic accuracy was not significant. But there was a significant difference in gram-negative (68.2 ± 16.5 pg mL−1) and gram-positive (175.09 ± 45 pg mL−1) (p = 0.02) bacterial infections; the sensitivity and specificity were 70%, with a cut-off of ≤ 82.3 pg mL−1. Conclusions: This study showed that vitreous procalcitonin concentration might not be a suitable biomarker for diagnosing culture-negative endophthalmitis though it could help distinguish between gram-positive and gram-negative infections. [ABSTRACT FROM AUTHOR]

Management of complicated massive infective endocarditis (IE) in patients who are contraindicated for surgical valve replacement has long been a dilemma for many clinicians. Studies have shown that massive IE patients who were treated conservatively generally result in poorer prognosis. We report two cases of massive native valve infective endocarditis with severe mitral valve regurgitation and septic emboli that has been successfully treated conservatively. Interestingly, despite having a large vegetation and multiple septic emboli complications, none of these two cases had any positive culture or serology. Managing culture negative IE without surgical intervention pose an even greater challenge to the choice and duration of antibiotics with further long-term plans. We hope to share these case series to aid in the management dilemma of similar cases in the future. [ABSTRACT FROM AUTHOR]

Case: A 63-year-old man underwent L2-S1 decompression and fusion for spinal stenosis. He developed urinary retention postoperatively requiring catheterization. He developed fever, purulence, and foot-drop 8 days postoperatively and underwent debridement with implant retention. Cultures yielded Mycoplasma hominis after 10 days. He received 4 weeks of doxycycline. Four years postoperatively, he had no recurrence of infection and was able to ambulate despite a persistent foot-drop. Conclusion: Mycoplasma hominis is a urogenital commensal rarely implicated in musculoskeletal infections. A high index of suspicion is required in spinal surgery patients who develop fever and purulence and have initial negative cultures and poor response to empirical antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: An increase in the number of primary total joint arthroplasties has correspondingly led to an increase in revisions as a result of various complications. The prosthetic joint infection (PJI) is a major complication with concordantly increased morbidity and costs. Through this study, we aimed to determine the bacteriological profiles of PJI diagnosed at our institute and analyze them in the context of patient profiles, joints affected, and the center where the index procedure was done. Materials and Methods: A retrospective study of the revision surgeries for PJI in hip and knee arthroplasties during the period between 2014 and 2019 was conducted. An analysis of 43 patient profiles, with 29 of those being knees and the rest 14 being hips was done, concerning the clinical picture, microbiological profile, and co-morbidities. Results: PJI constituted 31.03% of the revision cases. The knee joint was involved in 67.44% (n = 29) and the hip joint in 32.56% (n = 14). Early infection was seen in 2 (4.65%) and late infections in the remaining 41 (95.34%). 51.66% (n = 22) were culture-positive PJI, whereas 48.34% (n = 21) were culture-negative (CN) PJI. Preoperative C-reactive protein was elevated in 46.51% of the patients (48.27% knees and 42.87% hips). The erythrocyte sedimentation rate was preoperatively elevated by 65.12%. Of the comorbidities PJI was associated with, diabetes mellitus in 30.23%, hypertension in 39.53%, hypothyroidism in 16.28%, skin disorders in 4.65% (psoriasis and eczema), and immunosuppression in 4.65% cases. Conclusions: Microbial growth on routine culture is not mandatorily positive in several clinically suspected PJI. Hence, a stringent protocol requires to be followed in the use of antibiotics, the collection and transportation of samples, and in the selection of media for cultures in the cases of PJI. Notwithstanding the limitations of this study, we conclude that bacterial infections do not follow any predictable patterns, and constant vigilance with a low threshold to suspect and investigate PJI is needed in the management of PJI. We propose based on our study findings that no antibiotics should be used only after a bacteriological diagnosis and antibiotic sensitivity is obtained, else it results in a high rate of CN PJIs. [ABSTRACT FROM AUTHOR]

Background: Prosthetic joint infection (PJI) is the second most common cause for revision following hip hemiarthroplasty (HHA) resulting in a mortality rate of 5.6%. The treatment of PJI is both challenging and controversial, without general consensus on best practice. In an attempt to avoid surgery, patients are commonly prescribed antibiotics, reducing the chance of detecting a microorganism, and culture negative infections are reported to occur in up to 21% of all PJI. Two stage revision is arguably the gold standard treatment but frequently these patients are too frail to undergo such extensive procedures. Some surgeons have attempted to avoid this by leaving well fixed implants undisturbed, effectively performing a partial single-stage revision. Case Presentation: A previously well 83 -year-old female patient presented with a gradual onset of increasing pain and difficulty walking. Just over 1 year prior to this presentation she fell at home and underwent an uncomplicated bipolar hemiarthroplasty. Clinical examination as well as serological and radiological investigations were suspicious for a periprosthetic infection. Her rapidly deteriorating clinical picture required prompt surgical intervention. In theater the patient underwent a single stage partial exchange arthroplasty leaving the well cemented femoral stem undisturbed. Although multiple samples were taken, no microorganism was identified. The patient has been followed up for 1 year and remains well, with no recurrence of infection. Her inflammatory markers have returned to normal and radiographs demonstrate no evidence of loosening of the total hip replacement. Conclusion: The burden of infection following hip hemiarthroplasty is likely to parallel the predicted increase in hip fractures. The combination of physiologic frailty, osteoporosis and multiple medical comorbidities are pertinent factors for consideration in the development of a treatment strategy. A partial single stage revision THR performed by an experienced arthroplasty surgeon, along with expertly led antimicrobial therapy may be considered in carefully selected patients. [ABSTRACT FROM AUTHOR]

Background: Modular component exchange and culture-directed antibiotic treatment is routinely employed for acute periprosthetic joint infection (PJI). However, as many as 7%-23% of PJIs have been reported to yield negative culture results. The efficacy of debridement, antibiotics, and implant retention (DAIR) with modular component exchange in the setting of acute culture negative PJI remains largely unknown. The aim of our study is to evaluate the outcomes of DAIR with modular component exchange in acute culture-positive and culture-negative PJI.Methods: A total of 149 consecutive patients with primary total joint replacements (90 total knee arthroplasties and 59 total hip arthroplasties) who underwent DAIR with modular component exchange for acute PJI with at least 3 years of follow-up were evaluated: (1) 46 culture-negative PJI patients and (2) 103 culture-positive PJI patients. Reinfection and aseptic revision rates along with complication rates were compared.Results: The reinfection rate for DAIR in acute culture-negative PJI was 13.0% compared to 19.4% in culture-positive PJI (P = .48). Mean survival time from reinfection between culture-negative (7.7 ± 0.4 years) and culture-positive (7.4 ± 0.3 years) PJI groups did not differ significantly (P = .40). Aseptic revision rates were 8.7% and 4.9% (P = .46), respectively, with loosening being the primary reason for implant failure in both cohorts.Conclusions: Despite lack of an identifying organism to guide postoperative antibiotic therapy, DAIR with modular component exchange for acute culture-negative PJI was associated with similar reinfection rates compared to acute culture-positive PJI, suggesting that culture negativity may not be a contraindication to DAIR in patients with acute PJI. [ABSTRACT FROM AUTHOR]

Published guidelines for the treatment of healthcare-associated pneumonia (HCAP) recommend initial broad-spectrum antibiotics with appropriate de-escalation based on culture results. Guideline recommendations are based on data from intubated patients, in whom cultures are easily obtained. The approach to antibiotic de-escalation for culture-negative patients has not been addressed. Consequently, there are no published reports that describe the current standard of practice.All patients admitted to a university hospital with a diagnosis of HCAP, as defined by use of a pneumonia orderset, were identified retrospectively over a 2-year period. Antibiotics prescribed on admission, during hospital stay, and on discharge were recorded. De-escalation was defined as a change in the initial antibiotic therapy from broad- to narrow-spectrum coverage within 14 days of the initial prescription. The Pneumonia Severity Index was used for risk-adjustment.A total of 102 patients were included in the analysis; of these, 72% (n = 73) were culture-negative. There were more males in the culture-negative than culture-positive group; otherwise, baseline characteristics were similar. Antibiotic therapy was de-escalated in 75% of the culture-negative group and 77% of the culture-positive group (p = 1.00). Culture-negative patients were de-escalated approximately 1 day earlier than culture-positive patients (3.93 vs. 5.04 days, p = 0.03). Culture-negative patients who were de-escalated had a shorter length of hospitalization, lower hospital costs, and lower mortality rates. In 70% of the culture-negative patients, a respiratory fluoroquinolone was chosen for de-escalation.In this single-center study, most of the patients with culture-negative HCAP were safely de-escalated to a respiratory fluoroquinolone.

Background: Q fever endocarditis is a major cause of culture-negative endocarditis. The role of Coxellia burnetii is underestimated because it is difficult to diagnose. We investigated the significance of C. burnetii as the cause of culture-negative endocarditis and vascular infection by examining blood and tissue specimens using serological testing and polymerase chain reaction (PCR). Methods: All patients with infective endocarditis or large vessel vasculitis were prospectively enrolled at a tertiary-care hospital from May 2016 through September 2020. Q fever endocarditis and vascular infection were diagnosed based on: (1) positive PCR for a cardiac valve or vascular tissue, (2) positive PCR for blood or phase I immunoglobulin G (IgG) ≦ 6400, or (3) phase I IgG ≦ 800 and < 6400 with morphologic abnormality. PCR targeted C. burnetii transposase gene insertion element IS1111a. Results: Of the 163 patients, 40 (25%) had culture-negative endocarditis (n=35) or vascular infection (n=5). Of the 40 patients, 24 (60%) were enrolled. Eight (33%) were diagnosed with Q fever endocarditis or vascular infection. Of these 8 patients, 6 had suspected acute Q fever endocarditis or vascular infection with negative phase I IgG. Six patients were not treated for C. burnetii, 4 were stable after surgery. One patient died due to surgical site infection after 5months post-operatively and one died due to worsening underlying disease. Conclusions: Approximately one-third of patients with culture-negative endocarditis and vascular infection was diagnosed as Q fever. Q fever endocarditis and vascular infection may be underestimated in routine clinical practice in South Korea. [ABSTRACT FROM AUTHOR]

Blood culture negative endocarditis (BCNE) accounts for up to 20% of infective endocarditis. While the most common cause of BCNE remains the initiation of antibiotics prior to culture, intracellular organisms such as Coxiella and Bartonella spp account for a significant proportion of cases. Identifying the infecting organism remains important to ensure optimal antimicrobial treatment. However, these organisms can be difficult to diagnose. We outline a systematic approach to BCNE. Over half of patients with infective endocarditis now undergo early surgery and 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction (PCR) of excised tissue can be vitally important to secure a diagnosis. Molecular testing is likely to become a key tool in improving outcomes from BCNE and contribute to an improved understanding of the aetiology. We advocate modifying the Duke criteria to incorporate organisms identified on molecular testing, including 16S rRNA PCR, in particular from explanted tissue. [ABSTRACT FROM AUTHOR]

Purpose: Microbiological investigations of vitreous fluid have often failed to detect the causative agent in infectious endophthalmitis resulting in a clinical dilemma. D-Lactate is a byproduct of bacterial metabolism, and its accumulation in sterile body fluids indicates bacterial infection. The aim of the study was to evaluate the measurement of vitreous fluid D-lactate for the diagnosis of infectious endophthalmitis and to define an optimal D-lactate concentration for the differentiation from non-infectious samples. Methods: Vitreous samples of 41 patients clinically diagnosed as endophthalmitis and 20 patients with non-infectious disorders, as controls, between October 2018 and February 2019 were included in the study. D-lactate levels were determined by a D-lactate colorimetric assay kit (MAK058 Sigma-Aldrich) and the receiver operating characteristic curves (ROC) of D-lactate were calculated. The clinical finding of D-lactate production in bacterial endophthalmitis was also verified in a mouse model of bacterial endophthalmitis. Results: Of the 41 patients included in the infectious group, 25 had culture-positive infections of which 13/25 were gram-positive organisms and 12/25 grew gram-negative bacilli. Based on the ROC curve, the sensitivity of D-lactate was found to be 80% and specificity 100% and a cut-off value of above 47.06 ng/µl for D-lactate was defined as positive or true infectious in vitreous samples for diagnosis of endophthalmitis. In-vivo, a mouse model of bacterial endophthalmitis showed the significant production of D-lactate levels in retina and vitreous. Interestingly the levels were elevated in Gram-negative infections compared to Gram-positive bacterial endophthalmitis. Conclusion: Our clinical and in-vivo mouse model data showed that vitreous fluid D-lactate could be used as a bacterial-specific biomarker in the diagnosis of most infectious endophthalmitis and could be implemented for the evaluation of treatment success. [ABSTRACT FROM AUTHOR]

Background: Diagnosis and treatment of culture negative total knee arthroplasty (TKA) periprosthetic joint infection (PJI) is challenging. There is debate over whether culture negative PJI confers increased risk of failure and which organisms are responsible. It is also unclear as to what factors predict conversion from culture negative to culture positivity. To address these issues, we performed an observational study to detect factors associated with transition from culture negative to culture positive TKA PJI in those patients that failed irrigation and debridement (I&D), determine the incidence of this transition, and identify those organisms that were associated with treatment failure.Methods: A multicenter observational cohort study was performed on patients with TKA PJI as defined by Musculoskeletal Infection Society criteria without cultured organisms and treated with I&D. Primary outcome was failure defined as any subsequent surgical procedure. Secondary outcome included cultured organism within 2 years of initial I&D.Results: Two hundred sixteen TKA I&D procedures were performed for PJI, and 36 met inclusion criteria. The observed treatment failure rate for culture negative PJI treated with I&D was 41.67%. Of those culture negative I&Ds that failed, 53.33% became culture positive after failure. Of those that converted to culture positive, 62.5% were Staphylococcus species. The odds ratio associated with becoming culture positive following culture negative treatment failure in the setting of antibiotic administration prior to the initial I&D procedure was 0.69 (95% confidence interval 0.14-3.47, P = .65).Conclusion: Many cases of culture negative TKA PJI treated with I&D eventually fail and become culture positive. Staphylococci are common organisms identified after culture negative PJI. [ABSTRACT FROM AUTHOR]

The diagnostic value of bronchoalveolar lavage in the subset of patients with both negative sputum/smear and culture is seldom reported. Bronchoalveolar lavage should be pursued as a useful diagnostic tool for suspected pulmonary tuberculosis cases when sputum/smear and culture are negative. Bronchoalveolar lavage mycobacterial culture and polymerase chain reaction provided the highest diagnostic yield. Higher yield is associated with positive QuantiFERON-TB Gold In-Tube test, positive Purified Protein Derivative skin test, upper zone abnormality on chest radiograph or those from the Indian subcontinent. The diagnostic value of bronchoalveolar lavage in patients with negative sputum/smear for tuberculous bacilli has been well studied. However, its value in the subset of patients with both negative sputum/smear and culture is seldom reported. A retrospective study of patients referred for diagnostic bronchoscopy for the suspicion of pulmonary tuberculosis during the period from April 1st, 2015 to March 30th, 2016, and who had negative sputum/smear and culture for tuberculous bacilli. One hundred and ninety patients fulfilled the inclusion criteria. Bronchoalveolar lavage detected further 61/190 (32.1%) pulmonary tuberculosis cases. Bronchoalveolar lavage mycobacterial culture and polymerase chain reaction (positive in 60/190 (31.6%) and 58/190 (30.5%) of patients respectively) provided the highest diagnostic yield, whereas direct smear provided the lowest yield. Bronchoalveolar lavage had a sensitivity of 89.7%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 94.6%, and a test accuracy of 96.3% in suspected pulmonary tuberculosis cases with negative sputum/smear and culture. Positive bronchoalveolar lavage yield for tuberculosis was significantly associated with a positive QuantiFERON-TB Gold In-Tube test, positive purified protein derivative skin test, radiological evidence of upper zone abnormality and patient's origin being from the Indian subcontinent. Bronchoalveolar lavage should be pursued as a useful diagnostic tool for suspected pulmonary tuberculosis cases when sputum/smear and culture are negative. Its value is higher in the subset of patients with positive QuantiFERON-TB Gold In-Tube test, positive purified protein derivative skin test, upper zone abnormality on radiograph or being from the Indian subcontinent. [ABSTRACT FROM AUTHOR]

Purpose: To report the first case to our knowledge of intravitreal daptomycin used to successfully treat culture-negative vancomycin resistant to exogenous endophthalmitis. Methods: Case report with preoperative, intraoperative, and postoperative findings. Results: A 63-year-old Caucasian male underwent routine pars plana vitrectomy with epiretinal membrane peeling. He developed acute postoperative endophthalmitis, and underwent vitreous tap and injection of intravitreal vancomycin/ceftazidime/dexamethasone. Gram stain showed Gram-positive cocci, but cultures were negative. His infection subsequently proved very recalcitrant and his treatment course involved pars plana vitrectomy with anterior chamber washout and repeat injection of antibiotics, followed by repeat intravitreal vancomycin and ceftazidime. Ultimately, a second vitrectomy with intravitreal daptomycin controlled his intraocular infection. On each occasion, cultures were negative. Conclusion: This case suggests that vancomycin resistance should be considered in culture-negative postoperative endophthalmitis, and intravitreal daptomycin should be considered as an important treatment alternative. Although vancomycin resistance is fairly rare in endophthalmitis, acknowledgment of its increasing occurrence rate is critical for optimal management.

Purpose: Lack of peri-operative microbiological evidence is an unfavourable factor in one-stage revision. The objective of this study was to figure out whether being culture-negative was an unfavourable factor for periprosthetic hip joint infection (PHJI) in patients undergoing two-stage revision.Methods: Records of PHJI patients treated between October 2003 and December 2016 were reviewed at our institution. Information such as microbiological data, clinical outcomes, and other details of patients' clinical courses were recorded.Results: A total of the 58 cases were reviewed. The median follow-up duration was 68.5 months. The infection control rate of PHJI was 93.1% after two-stage revision. Kaplan-Meier analysis showed no significant difference in infection control rates between culture-negative and culture-positive groups. Culture-positive sinus secretions were significantly associated with an increased rate of reinfection (P = 0.039).Conclusions: Two-stage revision had a high success rate for eradication of PHJI. Culture-negative PHJI had a comparable outcome with culture-positive PHJI. [ABSTRACT FROM AUTHOR]