Nora Renz

Performance of automated multiplex PCR using sonication fluid for diagnosis of periprosthetic joint infection: a prospective cohort

PurposeSonication of explanted prostheses improved the microbiological diagnosis of periprosthetic joint infections (PJI). We evaluated the performance of automated multiplexxa0polymerase chain reaction (PCR) using sonication fluid for the microbiological diagnosis of PJI.MethodsIn a prospective cohort using uniform definition criteria for PJI, explanted joint prostheses were investigated by sonication and the resulting sonication fluid was analyzed by culture and multiplex PCR. McNemar’s Chi-squared test was used to compare the performance of diagnostic tests.ResultsAmong 111 patients, PJI was diagnosed in 78 (70%) and aseptic failure in 33 (30%). For the diagnosis of PJI, the sensitivity and specificity of periprosthetic tissue culture was 51 and 100%, of sonication fluid culture 58 and 100%, and of sonication fluid PCR 51 and 94%, respectively. Among 70 microorganisms, periprosthetic tissue culture grew 52 (74%), sonication fluid culture grew 50 (71%) and sonication fluid PCR detected 37 pathogens (53%). If only organisms are considered, for which primers are included in the test panel, PCR detected 37 of 58 pathogens (64%). The sonication fluid PCR missed 19 pathogens (predominantly oral streptococci and anaerobes), whereas 7 additional microorganisms were detected only by PCR (including Cutibacterium spp. and coagulase-negative staphylococci).ConclusionsThe performance of multiplex PCR using sonication fluid is comparable to culture of periprosthetic tissue or sonication fluid. The advantages of PCR arexa0short processing time (<xa05xa0h) and fully automated procedure. However, culture technique is still needed due to the low sensitivity and the need of comprehensive susceptibility testing. Modification of primers or inclusion of additional ones may improve the performance of PCR, especially of low-virulent organisms.

Synovial fluid multiplex PCR is superior to culture for detection of low-virulent pathogens causing periprosthetic joint infection

INTRODUCTIONnAnalysis of joint aspirate is the standard preoperative investigation for diagnosis of periprosthetic joint infection (PJI). We compared the diagnostic performance of culture and multiplex polymerase chain reaction (PCR) of synovial fluid for diagnosis of PJI.nnnPATIENTS AND METHODSnPatients in whom aspiration of the prosthetic hip or knee joint was performed before revision arthroplasty were prospectively included. The performance of synovial fluid culture and multiplex PCR was compared by McNemars chi-squared test.nnnRESULTSnA total of 142 patients were included, 82 with knee and 60 with hip prosthesis. PJI was diagnosed in 77 patients (54%) and aseptic failure in 65 patients (46%). The sensitivity of synovial fluid culture and PCR was 52% and 60%, respectively, showing concordant results in 116 patients (82%). In patients with PJI, PCR missed 6 high-virulent pathogens (S. aureus, streptococci, E. faecalis, E. coli) which grew in synovial fluid culture, whereas synovial fluid culture missed 12 pathogens detected by multiplex PCR, predominantly low-virulent pathogens (Cutibacterium acnes and coagulase-negative staphylococci). In patients with aseptic failure, PCR detected 6 low-virulent organisms (predominantly C. acnes).nnnCONCLUSIONnWhile the overall performance of synovial fluid PCR was comparable to culture, PCR was superior for detection of low-virulent bacteria such as Cutibacterium spp. and coagulase-negative staphylococci. In addition, synovial fluid culture required several days for growth, whereas multiplex PCR provided results within 5hours in an automated manner.

Value of PCR in sonication fluid for the diagnosis of orthopedic hardware-associated infections: Has the molecular era arrived?

INTRODUCTIONnBone healing disturbance following fracture fixation represents a continuing challenge. We evaluated a novel fully automated polymerase chain reaction (PCR) assay using sonication fluid from retrieved orthopedic hardware to diagnose infection.nnnPATIENTS AND METHODSnIn this prospective diagnostic cohort study, explanted orthopedic hardware materials from consecutive patients were investigated by sonication and the resulting sonication fluid was analyzed by culture (standard procedure) and multiplex PCR (investigational procedure). Hardware-associated infection was defined as visible purulence, presence of a sinus tract, implant on view, inflammation in peri-implant tissue or positive culture. McNemars chi-squared test was used to compare the performance of diagnostic tests. For the clinical performance all pathogens were considered, whereas for analytical performance only microorganisms were considered for which primers are included in the PCR assay.nnnRESULTSnAmong 51 patients, hardware-associated infection was diagnosed in 38 cases (75%) and non-infectious causes in 13 patients (25%). The sensitivity for diagnosing infection was 66% for peri-implant tissue culture, 84% for sonication fluid culture, 71% (clinical performance) and 77% (analytical performance) for sonication fluid PCR, the specificity of all tests was >90%. The analytical sensitivity of PCR was higher for gram-negative bacilli (100%), coagulase-negative staphylococci (89%) and Staphylococcus aureus (75%) than for Cutibacterium (formerly Propionibacterium) acnes (57%), enterococci (50%) and Candida spp. (25%).nnnCONCLUSIONnThe performance of sonication fluid PCR for diagnosis of orthopedic hardware-associated infection was comparable to culture tests. The additional advantage of PCR was short processing time (<5u202fh) and fully automated procedure. With further improvement of the performance, PCR has the potential to complement conventional cultures.

Infections After Cranial Neurosurgery: Prospective Cohort of 103 Episodes Treated According to a Standardized Algorithm

OBJECTIVEnThe optimal surgical and antimicrobial treatment for intracranial infections after neurosurgery is unknown. We investigated the clinical, laboratory, and microbiological characteristics of intracranial infections after neurosurgery. In addition, treatment outcome in patients treated according to a standardized algorithm was evaluated.nnnMETHODSnConsecutive patients with extradural, intradural, and device-related infections after cranial neurosurgery were included prospectively. A standardized antimicrobial and surgical treatment regimen was applied. The probability of infection-free survival was estimated by using the Kaplan-Meier survival method. Survival curves between groups were compared by using log-rank Mantel-Cox test.nnnRESULTSnOf 103 infections, 58 (56%) were extradural, 33 (32%) intradural, and 12 (12%) device-associated. Foreign material was involved in 98 infections (95%), including 78 bone flaps or fixation devices, 41 duraplasties, 17 external drains, and 15 functional devices. The median duration from primary surgery until infection diagnosis was 33 days (range, 6-1132 days). In total, 69 infections (67%) were monomicrobial, 26 (25%) polymicrobial, and 8 (8%) culture-negative. Ninety of 103 patients (90%) underwent surgical intervention, of whom foreign material was retained in 24 (23%). The probability of infection-free survival was 87% after 12 months (95% confidence interval 77%-93%). Nonadequate antimicrobial therapy was associated with treatment failure (5% vs. 70%, P < 0.001), which remained significant in the multiple logistic regression model (Pxa0= 0.01).nnnCONCLUSIONSnMost (95%) intracranial infections were associated with foreign material and required surgical intervention and biofilm-active treatment. Via a standardized treatment approach, the infection-free survival after 12 months was good (87%), independent of the infection site or type of micro-organism.

Orthopedic implant-associated infections caused by Cutibacterium spp. – A remaining diagnostic challenge

Background The definition criteria and clinical characteristics of implant-associated infection (IAI) caused by Cutibacterium (formerly Propionibacterium) spp. are poorly known. We analyzed microbiologically proven Cutibacterium orthopedic IAI in a prospective cohort. Methods Patients with periprosthetic joint infections (PJI) and fixation device–associated infections (FDAI) caused by Cutibacterium spp. were prospectively included. IAI was defined by significant growth of Cutibacterium spp. and presence of at least one non-microbiological criterion for infection. The McNemar’s chi-squared or binomial test was used to compare the performance of diagnostic tests. Results Of 121 patients with Cutibacterium IAI, 62 patients (51%) had PJI and 59 (49%) had FDAI. 109 infections (90%) were caused by C. acnes and 12 (10%) by C. avidum. The median time from implantation until diagnosis of infection was 15.7 months (interquartile range, 5–46.5 months). Clinical local signs were present in 30 patients (28%) and radiological implant loosening in 64 patients (63%). Culture sensitivity of sonication fluid was 84%, of peri-implant tissue 84% and of synovial or peri-implant fluid 56% after 14 days of incubation. Conclusion Cutibacterium IAI was diagnosed late in the disease course and presented with subtle signs. Prolonged culture incubation and implant sonication improved the poor performance of conventional microbiological tests. Due to lack of reliable diagnostic tests, Cutibacterium remains difficult to detect making the diagnosis challenging.

Sonication Improves Pathogen Detection in Ventriculoperitoneal Shunt-Associated Infections

BACKGROUNDnAntimicrobial treatment of ventriculoperitoneal (VP) shunt infections is challenging when the causative pathogen is unknown.nnnOBJECTIVEnTo evaluate the value of sonication of explanted shunt-devices to improve the microbiological detection rate.nnnMETHODSnAll consecutive patients undergoing revision surgery due to suspected VP-shunt infection from January 2015 to February 2017 were evaluated. Intraoperative tissue samples, wound swabs, and cerebrospinal fluid (CSF) were collected for microbiological examination. In a subgroup of patients, the removed implants were additionally sent for sonication.nnnRESULTSnA total of 35 patients were included with a mean age of 57.5xa0±xa018 yr, 21 were female (60%). In 13 patients tissue samples, CSF and wound swabs were analyzed. In 22 patients, the explanted device was additionally sent for sonication. All 22 sonication cultures showed a positive microbiological result (100%), whereas with conventional microbiological methods, the causative microorganism was identified in 8 of 13 (61%; Pxa0=xa0.018). Analyzed by method, all 22 sonication cultures (100%) were positive and 21 of 35 conventional microbiological analysis results (60%) detected the causative agent (Pxa0<xa0.001.) In 18 patients (51%), antimicrobial treatment was started preoperatively. In those patients, the pathogen was detected in all 12 sonication cultures (100%), whereas conventional methods grew a pathogen in 3 of 6 patients (Pxa0=xa0.005).nnnCONCLUSIONnSonication significantly increases the microbiological yield in VP-shunt infections, especially in patients receiving antibiotics prior to diagnostics and in infections caused by low-virulent organisms. The implementation of sonication into the clinical routine can substantially increase the rate of pathogen detection allowing targeted treatment.

Antibiotic-induced fever in orthopaedic patients—a diagnostic challenge

IntroductionAntibiotic-induced fever is a probably underestimated complication, which may be misdiagnosed as new infection. In this study, characteristics, diagnostic approach, and outcome of antibiotic-induced fever in patients treated for musculoskeletal infections are described.MethodsWe retrospectively reviewed all patients with antibiotic-induced fever after surgery treated at our institution from 2014 to 2017. Antibiotic-induced fever was diagnosed, if the following criteria were fulfilled: (i) central (ear) body temperature >u200938.0xa0°C; (ii) intravenous antibiotics for >u2009threexa0days; (iii) exclusion of infectious or other non-infectious causes of fever; and (iv) defervescence after discontinuation of antibiotics.ResultsWe included 11 patients (median age 51xa0years) treated for infection after fracturexa0fixation (nu2009=u20095), periprosthetic joint infections (nu2009=u20093), infection after spinal instrumentation (nu2009=u20091), and soft tissue infection (nu2009=u20092). The suspected antibiotics inducing fever were beta-lactam antibiotics (nu2009=u20099), vancomycin (nu2009=u20093), daptomycin (nu2009=u20092), clindamycin, and meropenem (nu2009=u20091 each). Additional clinical findings were reduced general condition, generalized exanthema, and rigors, whereas five patients were asymptomaticxa0apart from a fever. Leukopenia was observed in nine patients and increase of C-reactive protein value in ten patients. Fever occurred after a median of 20xa0days of antibiotic treatment and resolved after a median of onexa0day after discontinuation of the suspected antibiotic.ConclusionsAntibiotics should be considered as the possible cause of fever in orthopaedic patients receiving antimicrobial treamentxa0whenever clinical signs of new or persisting infection are lacking. Important hints suggestive for antibiotic-induced fever are good general condition despite high temperature and progressive leukopenia. Discontinuation or change to another substance leads to prompt defervescence, preventing unnecessary diagnostic procedures and antibiotic treatment.

Management of Periprosthetic Joint Infection

Periprosthetic joint infection (PJI) is a serious complication after arthroplasty, which is associated with pain, prolonged hospital stay, multiple surgeries, functional incapacitation, and even mortality. Using scientific and efficient management protocol including modern diagnosis and treatment of PJI and eradication of infection is possible in a high percentage of affected patients. In this article, we review the current knowledge in epidemiology, classification, pathogenesis, diagnosis and treatment of PJI.

Origin and Characteristics of Haematogenous Periprosthetic Joint Infection

OBJECTIVESnRecognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI.nnnMETHODSnConsecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection ≥1xa0month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fishers exact, Students t and Mann-Whitney U tests were used, as appropriate.nnnRESULTSnA total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and onexa0elbow prostheses. The median time from last surgery until haematogenous PJI was 47xa0months (range, 1-417xa0months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (nxa0=xa043), streptococci (nxa0=xa032), enterococci (nxa0=xa013), Gram-negative bacteria (nxa0=xa09) and coagulase-negative staphylococci (nxa0=xa08). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes).nnnCONCLUSIONSnIn acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.