Surgical site infection after pelvic bone and soft tissue sarcoma resection: Risk factors, microbiology, and impact of extended postoperative antibiotic prophylaxis.

BACKGROUND: Pelvic bone and/or soft tissue sarcoma removal surgeries are associated with a high rate of surgical site infection (SSI). The recommended antibiotic prophylaxis (ABP) duration is 24-48 h. We aimed to assess the impact of extended ABP (5 days) on the SSI rate and describe the microbiology of SSI in bone and/or soft tissue pelvic sarcomas. METHODS: We retrospectively included all consecutive patients who underwent pelvic bone and/or soft tissue sarcoma removal surgery between January 2010 and June 2020. RESULTS: We analyzed 146 patients with pelvic bone (45, 31%) or soft tissue (101, 69%). Sixty patients (41%) developed SSI. SSI occurred in 13/28 (46.4%) in the extended ABP group versus 47/118 (39.8%) in the standard group (p = 0.53). In multivariable analysis, risk factors for SSI were surgery duration (OR: 1.94 [1.41-2.92] per h), stay in postoperative ICU for more than 2 days (12.0 [2.8-61.3]), and shred or autologous skin flap (39.3 [5.8-409.5]). Extended ABP was not associated with SSI. SSI were mainly polymicrobial with Enterobacterales (57.4%) and Enterococcus (45%). CONCLUSIONS AND DISCUSSION: Pelvic bone and/or soft tissue sarcoma removal surgery is highly prone to postoperative infection. Extending the ABP to 5 days does not reduce the level of SSI.

Oral levofloxacin: population pharmacokinetics model and pharmacodynamics study in bone and joint infections.

OBJECTIVES: This study aimed at characterizing the pharmacokinetics (PK) of oral levofloxacin in adult patients in order to optimize dosing scheme and explore the PK/pharmacodynamics (PD) of levofloxacin in bone and joint infections (BJIs). METHODS: From November 2015 to December 2019, all patients hospitalized in Cochin Hospital, treated with levofloxacin and who had at least one dosage for therapeutic drug monitoring were included. PK was described using non-linear mixed-effect modelling. In a subgroup of patients with BJIs, the association between PK, MIC for the isolated pathogen and clinical outcome was investigated. Monte Carlo simulations investigated dosing regimens to achieve the PK/PD target (AUC/MIC ratio >100). RESULTS: One hundred and two patients were included (199 measurements), including 32 treated for BJI. A one-compartment model with first-order absorption and elimination best described the data. Effects of estimated creatinine clearance (eCLCR) and age were significant on levofloxacin clearance. In BJI patients, no significant association was found between levofloxacin PK/microbiological parameters and either clinical outcome or adverse events. Based on our model, we proposed optimized oral levofloxacin dosing regimens according to renal function, to reach the PK/PD target AUC/MIC ratio >100 for three frequent causative pathogens (Staphylococcus aureus, Enterobacterales and Pseudomonas aeruginosa). CONCLUSIONS: Our results reinforce the need of determining the MIC and using therapeutic drug monitoring in complex infections caused by P. aeruginosa.

Were protective procedures against SARS-CoV-2 effective in an orthopaedic and trauma centre during the lockdown period? A retrospective study.

PURPOSE: The SARS-CoV-2 epidemic started in December 2019 in Wuhan. The lockdown was declared on March 16, 2020 in France. Our centre had to adapt daily practices to continue to take care of bone and soft tissue tumours and emergencies. Through this study, we wanted to assess the various procedures implemented during the lockdown period between March 17 and May 10. METHODS: A monocentric retrospective cohort study was conducted in Cochin Hospital (Paris, France). Patients included were those who had surgery during the lockdown period. To take care of COVID-19 positive and negative patients, various procedures have been set up: reverse transcriptase polymerase chain reaction (RT-PCR) tests for all hospitalized patients, a specific unit for COVID-positive patients, a specific surgical room, and use of protective personal equipment. To allow the effectiveness of the procedures implemented, we evaluated the number of complications attributed to SARS-CoV-2 and the number of patients who became COVID positive during hospitalization. RESULTS: During the lockdown period, there were 199 procedures of three types of procedures in our centre: 79 traumatology procedures (39.7%), 76 of bone and soft tissues tumours (38.2%), and 44 procedures related to infection (22.1%). We observed 13 complications (6.5%) during hospitalization, and only one patient became COVID-19 positive during the hospitalization. CONCLUSION: The COVID-19 epidemic has been a challenge for organization and adaptation to manage all COVID-19 positive and COVID negative. Through this study, we wanted to assess our procedures taken. They had been effective due to the low number of contamination and complications.

Impact of Sequential Culture Results on Diagnosis and De-Escalation of the Antibiotic Regimen in Joint and Bone Infections.

BACKGROUND: According to existing guidelines, orthopedic specimens collected in joint and bone infections (JBI) in our institution are cultured on several media sets and incubated for two, seven, and 14 days. The optimal timing for de-escalation of the first-line antibiotic combination according to the culture results needs to be defined. METHODS: Single-center, retrospective analysis of all adult patients with a first documented episode of JBI between May 2012 and April 2013. RESULTS: Ninety patients were included, 51 males (57%), median age 58 y (range 18-87 y), with prosthesis infection in 62 cases (69%). Rapidly growing pathogens (Staphylococcus aureus [n = 36] and Enterobacteriaceae [n = 12]) usually were diagnosed within two days, whereas coagulase-negative staphylococci (n = 25) and Propionibacterium acnes (n = 13) generally were identified after seven days (p < 10-5). Positive culture results at day 2 fit with definitive microbiological diagnosis in 95% of cases, and prolonged incubation led to the identification of additional micro-organisms in only four of 76 patients (5%) with day-2-positive cultures. Conversely, for those with negative two-day culture (n = 14), the seven-day culture allowed identification of less virulent pathogens in eight cases (57%). CONCLUSIONS: Our results suggest that, in JBI, de-escalation of the empirical antibiotic regimen can be based on micro-organisms identified on the two-day culture set. The impact of such a strategy on clinical outcomes, antibiotic consumption, and costs needs to be assessed in larger studies.

High Frequency of Polymicrobial Infections After Surgical Resection of Malignant Bone and Soft Tissue Tumors: A Retrospective Cohort Study.

INTRODUCTION: Surgical resection of a malignant bone tumor (BT) or soft tissue tumor (STT), with or without prosthetic replacement, carries a high risk of developing postoperative infections. There is limited knowledge on the bacteriological spectrum of these postsurgical infections that necessitate empirical antibiotic therapy. The aim of this study was to analyze the incidence and microbiological features of site infections following BT or STT resection. METHODS: In this retrospective mono-center study, we analyzed the surgical and bacteriological data of all consecutive patients who developed an infection after surgical resection of a BT or STT between January 2010 and April 2014. RESULTS: Seventy-two consecutive patients who developed an infection on the site of surgical treatment for a BT (n = 42) or SST (n = 30) were included. Polymicrobism was frequently observed, more often associated with STTs (93%) than BTs (71%; P = 0.03). Gram-negative bacteria were more frequently isolated in STTs (55%) than in BTs (26%; P = 0.01) and non-prosthesis-associated infections (54%) than prosthesis-associated infections (29%; P = 0.04), whereas staphylococci were more frequently found in BTs (76%) than in STTs (52%; P = 0.03). Overall, we found gram negatives in 82% of early acute infections, 11% of chronic infections and 7% of late acute infections (P < 0.01). CONCLUSION: Postoperative infections in patients after surgical resection of BTs or STTs were often polymicrobial, especially following STTs. Causative bacteria were often gram negatives in STTs and non-prosthesis-associated infections, whereas staphylococci were predominant in BTs. Based on these findings, we recommend antibiotic coverage of both gram-positive and -negative bacteria with a combination of broad-spectrum antibiotics in STTs and antistaphylococcal antibiotics as first-line therapy in infections following BT surgery.

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.

PURPOSE: Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome. METHODS: An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L. RESULTS: Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin. CONCLUSIONS: This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

Specific distribution within the Enterobacter cloacae complex of strains isolated from infected orthopedic implants.

Bacteria belonging to the Enterobacter genus are frequently isolated from clinical samples but are unusual causative agents of orthopedic implant infections. Twelve genetic clusters (clusters I to XII) and one sequence crowd (sequence crowd xiii) can be distinguished within the Enterobacter cloacae nomenspecies on the basis of hsp60 sequence analysis, and until now, none of these clusters could be specifically associated with a disease. In order to investigate if specific genetic clusters would be involved in infections of orthopedic material, two series of bacterial clinical isolates identified as E. cloacae by routine phenotypic identification methods were collected either from infected orthopedic implants (n = 21) or from randomly selected samples of diverse anatomical origins (control; n = 52). Analysis of the hsp60 gene showed that genetic clusters III, VI, and VIII were the most frequent genetic clusters detected in the control group, whereas cluster III was poorly represented among the orthopedic implant isolates (P = 0.006). On the other hand, E. hormaechei (clusters VI and VIII), but not cluster III, is predominantly associated with infections of orthopedic implants and, more specifically, with infected material in the hip (P = 0.019). These results support the hypothesis that, among the isolates within the E. cloacae complex, E. hormaechei and hsp60 gene sequencing-based cluster III are involved in pathogenesis in different ways and highlight the need for more accurate routine Enterobacter identification methods.

Acute pancreatitis related to tigecycline: case report and review of the literature.

Tigecycline is a new broad-spectrum antibiotic. Nausea and vomiting are its most common side-effects. We describe here a case of severe acute pancreatitis related to tigecycline in order to highlight the possible occurrence of this adverse event and to remind clinicians to measure the lipase rate if in any doubt.