Clinical practice recommendations for infectious disease management of diabetic foot infection (DFI) - 2023 SPILF.

In march 2020, the International Working Group on the Diabetic Foot (IWGDF) published an update of the 2015 guidelines on the diagnosis and management of diabetic foot infection (DFI). While we (the French ID society, SPILF) endorsed some of these recommendations, we wanted to update our own 2006 guidelines and specifically provide informative elements on modalities of microbiological diagnosis and antibiotic treatment (especially first- and second-line regiments, oral switch and duration). The recommendations put forward in the present guidelines are addressed to healthcare professionals managing patients with DFI and more specifically focused on infectious disease management of this type of infection, which clearly needs a multidisciplinary approach. Staging of the severity of the infection is mandatory using the classification drawn up by the IWGDF. Microbiological samples should be taken only in the event of clinical signs suggesting infection in accordance with a strict preliminarily established protocol. Empirical antibiotic therapy should be chosen according to the IWGDF grade of infection and duration of the wound, but must always cover methicillin-sensitive Staphylococcus aureus. Early reevaluation of the patient is a fundamental step, and duration of antibiotic therapy can be shortened in many situations. When osteomyelitis is suspected, standard foot radiograph is the first-line imagery examination and a bone biopsy should be performed for microbiological documentation. Histological analysis of the bone sample is no longer recommended. High dosages of antibiotics are recommended in cases of confirmed osteomyelitis.

Explicit definitions of potentially inappropriate prescriptions of antibiotics in hospitalized older patients.

CONTEXT: The use of explicit definitions of potentially inappropriate prescriptions of antibiotics (antibiotic PIPs) might constitute an innovative means to fight against antimicrobial resistance. Explicit definitions of PIPs can reduce the rate of inappropriate prescriptions, but explicit definitions of antibiotic PIPs in geriatric medicine are currently lacking. The objective of the study was to develop explicit definitions of antibiotic PIPs for hospitalized older patients. METHOD: We performed a qualitative study of focus groups involving geriatricians and infectious disease specialists. The study complied with the Consolidated Criteria for Reporting Qualitative Research. Transcripts of audio recordings were analyzed in a two-step independent reviewing process. The exact wording of the definitions was validated by a steering committee, an independent expert group, and the focus group participants. RESULTS: The four focus groups comprised 28 stakeholders. Our analysis identified 65 explicit definitions of antibiotic PIPs: 47 (73%) concerned misuse, 15 (23%) concerned overuse and three (5%) concerned underuse. Most definitions were related to critically important antibiotics: 11 (17%) for fluoroquinolones, eight (12%) for amoxicillin-clavulanic acid, eight (12%) for cephalosporins, seven (11%) for aminoglycosides, and five (8%) for carbapenems. CONCLUSION: To address the public health challenge of antimicrobial resistance, our study generated explicit definitions for antibiotic PIPs in older patients. We intend to refine and to validate these definitions through a national Delphi survey; the resulting consensus might provide key messages for prescribers and open up perspectives for reducing the incidence of antibiotic PIPs.

Importance of Footwear Outsole Rigidity in Improving Spatiotemporal Parameters in Patients with Diabetes and Previous Forefoot Ulcerations.

We aimed to identify if any differences existed in spatiotemporal parameters during gait among different densities of rocker soles in patients with a history of neuropathic ulcerations and the differences in comfort between shoe conditions. This study was a cross-sectional study of 24 patients with diabetes and a history of neuropathic diabetic foot ulcers (DFUs). Spatiotemporal parameters (duration of stance phase (ms), stride length (cm), and step velocity (m/s)) were analyzed in barefoot, semirigid outsole, and rigid outsole footwear conditions. A dynamic pressure measurement system (Footscan® system, RSscan International, Belgium) was used to assess shoe conditions. We also analyzed differences in comfort between the shoe conditions using a visual analog scale. A Wilcoxon test for paired samples was used to assess gait differences. Result showed that a rigid outsole causes changes in the subphases of the stance phase (p < 0.001; Cohen d = 0.6) compared to a semirigid outsole. Stride length (p < 0.001; Cohen d = 0.66) and step velocity were significantly longer (p < 0.001; Cohen d = 2.03) with the use of rigid outsole footwear. A rigid rocker sole reduces the time of the stance phase, in addition to increasing the stride length and velocity of step in patients with a previous history of DFUs.

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study.

OBJECTIVES: The aim was to describe the effectiveness of suppressive antibiotic treatment (SAT) in routine clinical practice when used in situations in which removal of a prosthetic implant is considered essential for the eradication of an infection, and it cannot be performed. METHODS: This was a descriptive retrospective and multicentre cohort study of prosthetic joint infection (PJI) cases managed with SAT. SAT was considered to have failed if a fistula appeared or persisted, if debridement was necessary, if the prosthesis was removed due to persistence of the infection or if uncontrolled symptoms were present. RESULTS: In total, 302 patients were analysed. Two hundred and three of these patients (67.2%) received monotherapy. The most commonly used drugs were tetracyclines (39.7% of patients) (120/302) and cotrimoxazole (35.4% of patients) (107/302). SAT was considered successful in 58.6% (177/302) of the patients (median time administered, 36.5 months; IQR 20.75-59.25). Infection was controlled in 50% of patients at 5 years according to Kaplan-Meier analysis. Resistance development was documented in 15 of 65 (23.1%) of the microbiologically documented cases. SAT failure was associated with age <70 years (sub-hazard ratio (SHR) 1.61, 95% CI 1.1-2.33), aetiology other than Gram-positive cocci (SHR 1.56, 95% CI 1.09-2.27) and location of the prosthesis in the upper limb (SHR 2.4, 95% CI 1.5-3.84). SAT suspension was necessary due to adverse effects in 17 of 302 patients (5.6%). CONCLUSIONS: SAT offers acceptable results for patients with PJI when surgical treatment is not performed or when it fails to eradicate the infection.

Factors of loss to follow-up during tuberculosis treatment in a low-incidence region.

OBJECTIVE: The proportion of successfully treated tuberculosis (TB) patients remains below the WHO target in France, because of a high proportion of loss to follow-up. We aimed to identify factors associated with loss to follow-up in northern France, a low-incidence area. METHODS: Between 1997 and 2017, all consecutive patients diagnosed with TB at the Tourcoing Hospital, except those infected with multidrug-resistant or extensively drug-resistant strains, were included in a retrospective cohort study. A logistic regression analysis was performed to determine factors associated with loss to follow-up. RESULTS: One hundred and ninety patients were included. Previous TB treatment was reported in 32 patients (17%), extrapulmonary TB in 107 (56%), and HIV infection in 44 (23%). The proportion of loss to follow-up was 15%. In multivariate analysis, the risk of loss to follow-up decreased in case of first TB treatment (OR 0.36; 95% CI: 0.14-0.92, P=0.03) and increased in non-HIV-infected patients (OR 7.67; 95% CI: 1.00-59.0, p=0.05). Support for compliance was more frequent in HIV-infected patients (23% vs. 7%, p=0.005). CONCLUSION: The proportion of loss to follow-up was high. HIV infection was associated with a lower risk of loss to follow-up, likely to be due to more frequent support for compliance.

Pathogenesis and management of fracture-related infection.

BACKGROUND: Both fracture-related infections (FRIs) and periprosthetic joint infections (PJIs) include orthopaedic implant-associated infections. However, key aspects of management differ due to the bone and soft tissue damage in FRIs and the option of removing the implant after fracture healing. In contrast to PJIs, research and guidelines for diagnosis and treatment in FRIs are scarce. OBJECTIVES: This narrative review aims to update clinical microbiologists, infectious disease specialists and surgeons on the management of FRIs. SOURCES: A computerized search of PubMed was performed to identify relevant studies. Search terms included 'Fracture' and 'Infection'. The reference lists of all retrieved articles were checked for additional relevant references. In addition, when scientific evidence was lacking, recommendations are based on expert opinion. CONTENT: Pathogenesis, prevention, diagnosis and treatment of FRIs are presented. Whenever available, specific data of patients with FRI are discussed. IMPLICATIONS: Management of patients with FRI should take into account FRI-specific features. Treatment pathways should implement a multidisciplinary approach to achieve a good outcome. Recently, international consensus guidelines were developed to improve the quality of care for patients suffering from this severe complication, which are highlighted in this review.

Pubic osteomyelitis: Epidemiology and factors associated with treatment failure.

OBJECTIVE: To describe the epidemiology of pubic osteomyelitis (PO) and to look for factors associated with treatment failure. METHOD: Retrospective study describing PO according to outcome: success or failure of initial management. Factors associated with failure determined by univariate Cox analysis. Kaplan-Meier curve compared between groups by log-rank test. RESULTS: Twenty-five patients were included over a 13-year period; 24% of PO had blood-borne infection. Failure (44%) was always observed in chronic postoperative presentations (76%). Fistula (32%) was only observed in postoperative presentations and was significantly associated with failure (HR 5.1; P=0.011). Other risk factors were pelvic malignant tumor history, abscess, infection due to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and polymicrobial infection. CONCLUSION: PO is most often a chronic postoperative polymicrobial infection in patients with comorbidities at high risk of relapse. Studies in larger cohorts could assess the efficacy of more aggressive surgical strategies in patients at high risk of failure.

Daptomycin versus Vancomycin as Post-Operative Empirical Antibiotic Treatment for Prosthetic Joint Infections: A Case-Control Study.

Purpose: To compare safety and efficacy of Vancomycin (Van) versus Daptomycin (Dap) as post-operative empirical antibiotic treatment (PEAT) in patients with periprosthetic joint infections (PJIs). Methods: Medical charts of patients treated empirically with Van or Dap in the post-operative period of total hip/knee prosthesis septic revision until the results of intra-operative culture were reviewed. Cefotaxime, cefepime or aztreonam were used in combination with Dap or Van. Results: Twenty Dap patients were matched with 20 other Van patients according to the age and type of prosthesis. The ASA score and the distribution of the pathogens was similar in the two groups especially regarding the number of methicillin-resistant staphylococci. The mean duration of the PEAT was 6.07 ± 0.85 days. A total of 17 episodes of adverse events (AE) in 10 patients (25%) were recorded during the PEAT which led to discontinue the treatment in 5 patients, all of them treated with Van (P=0.02). At the end of a mean post-treatment follow-up of 618 +/- 219 days, 36 patients remained in remission of infection; 2 patients failed in each group. Conclusions: Our observations suggest that PEAT with Van for septic revision of PJIs is associated with a higher discontinuation rate due to AE but with a similar outcome than it is with Dap.

[Antibiotic prophylaxis in urodynamics: Clinical practice guidelines using a formal consensus method]. / Antibioprophylaxie et bilan urodynamique : recommandations de bonne pratique par consensus formalisé.

OBJECTIVE: The aim of this work was to issue clinical practice guidelines on antibiotic prophylaxis in urodynamics (urodynamic studies, UDS). MATERIALS AND METHODS: Clinical practice guidelines were provided using a formal consensus method. Guidelines proposals were drew up by a multidisciplinary experts group (pilot group = steering group), then rated by a panel of 12 experts (rating group) using a formal consensus method, and then peer reviewed by a reviewing/reading group of experts (different from the rating group). RESULTS: Urine (bacterial) culture with antimicrobial susceptibility testing is recommended for all patients before UDS (strong agreement). In patients with no neurologic disease, the risk factors for tract urinary infection (UTI) after UDS are age > 70 years, recurrent UTI, and post-void residual volume > 100ml. In patients with neurologic disease, the risk factors for UTI after UDS are recurrent UTI, vesicoureteral reflux, and intermicturition pressure > 40cmH2O. If the urine culture is negative before UDS and there is no risk factor for UTI, antibiotic prophylaxis is not recommended (Strong agreement). If the urine culture is negative before UDS, but there are one or more risk factors for UTI, antibiotic prophylaxis is optional. If antibiotic prophylaxis is initiated, a single oral dose (3g) of fosfomycin-tromethamine two hours before UDS is recommended (Strong agreement). If there is bacterial colonization on UCB before UDS, antibiotic therapy is optional (Undecided). If prescribed, it should be adapted to the antimicrobial susceptibility of the identified bacterium or bacteria, started the day before and stopped after UDS (except for fosfomycin-tromethamine: a single dose the day before UDS is necessary and sufficient) (Strong agreement). In the event of UTI before UDS, the UTI should be treated and UDS postponed (Strong agreement). The proposed recommendations should not be changed for patients with a hip or knee replacement (Strong agreement). No antibiotic prophylaxis of bacterial endocarditis is necessary, including in high-risk patients with valvular heart disease (Strong agreement). CONCLUSION: These new guidelines should help to harmonize clinical practice and limit exposure to antibiotics. LEVEL OF EVIDENCE: 4.

Prospective evaluation of the management of urinary tract infections in 134 French nursing homes.

OBJECTIVE: Prospective assessment of the management of urinary tract infections (UTI) in the nursing homes of the Hauts-de-France region. PATIENTS AND METHODS: A 50-question form had to be filled in for up to five consecutive residents treated for UTI in each nursing home. If necessary, diagnoses were reclassified according to the 2014 French Infectious Diseases Society guidelines. Analyses were presented per supposed (reported) and reclassified diagnoses. RESULTS: Of 397 contacted facilities, 134 participated and informed 444 UTI episodes. Reported diagnostic criteria were burning urination (32%), malodorous urine (29%), confusion (28%), and turbid urine (19%). Twenty-one percent of diagnoses were based on erroneous criteria. Less than 50% of residents had a urine dipstick test performed and 94% a urine culture. The main pathogen was Escherichia coli. Reported indications were uncomplicated cystitis (32%), unspecified UTI (26%), complicated cystitis (9%), while no reason was given in 25% of cases. Only 10% of diagnoses were consistent with the guidelines: complicated cystitis (49%), asymptomatic bacteriuria (21%), acute pyelonephritis (21%), male UTI (9%). Almost 85% of prescriptions were active on the isolated bacteria. The empirical antibiotic therapy was consistent with the diagnosis in 16% of cases (30% for reclassified diagnoses). The two most prescribed antibiotic classes were fluoroquinolones (22.1%) and oral third-generation cephalosporins (19.1%). Only two of 157 possible de-escalations were performed. Duration of treatment was adequate for 19% of UTIs (9.6% of reclassified cases). CONCLUSION: Our study revealed multiple deficiencies in diagnosis, antibiotic choice, treatment duration, and reevaluation.

Diagnostic accuracy of the alpha defensin lateral flow device (Synovasure) for periprosthetic infections in microbiologically complex situations: A study of 42 cases in a French referral centre.

BACKGROUND: Joint aspiration is currently the reference standard test for diagnosing periprosthetic joint infection (PJI) despite the high rate of false-negative results, of which a major cause is the fastidious nature of some microorganisms. A rapid diagnostic test that detects alpha defensin (Synovasure™, Zimmer, Warsaw, IN, USA) in joint fluid can provide the diagnosis of PJI within a few minutes across the full spectrum of causative organisms (including mycobacteria and yeasts). Its performance in detecting bacterial infections is unaltered by concomitant antibiotic therapy. Few studies of Synovasure™ have been conducted by groups that were involved in designing the test, which has not been validated in France. Assessments in referral centres where complex microbiological situations are common hold considerable interest. The objective of this prospective study was to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and causes of error of Synovasure™ used to diagnose periprosthetic infection in complex microbiological situations. HYPOTHESIS: The rapid diagnostic test Synovasure™ has greater than 90% NPV for detecting periprosthetic infections in complex microbiological infections. MATERIAL AND METHODS: Synovasure™ was used 42 times in 39 patients between October 2015 and October 2017 in challenging microbiological situations [discordant joint aspiration results (n=20), negative cultures with clinical or laboratory evidence of infection, (n=21), and concomitant antibiotic therapy (n=1)]. Of the 39 patients, 23 had total knee prostheses, 13 total hip prostheses, and 3 total femoral prostheses. The reference standard to which the Synovasure™ results were compared was the PJI criteria set developed by the Musculoskeletal Infection Society (MSIS). RESULTS: Synovasure™ was negative in 30 cases with negative joint fluid cultures (30/42, 71.4%). Of the 12 (28.6%) cases with positive Synovasure™ results, only 7 (7/12, 58.3%) had positive joint fluid cultures. According to the MSIS criteria 9 cases were infected, including 8 with positive and 1 with negative Synovasure™ results. Of the 33 cases that were not infected according to MSIS criteria, 29 had negative and 3 positive Synovasure™ results; the remaining case had a positive Synovasure™ result but was excluded when metallosis was found intra-operatively. NPV was 96.7%, PPV 72.7%, sensitivity 88.9%, and specificity 90.6%. DISCUSSION: The high NPV of Synovasure™ suggests a role for this test in microbiologically complex situations as a new tool for ruling in and, most importantly, ruling out infection in doubtful cases. LEVEL OF EVIDENCE: III, prospective study of diagnostic accuracy.

Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients.

The aim of this study was to describe the use of oral doxycycline as suppressive antibiotic therapy (SAT) in patients with Staphylococcus aureus periprosthetic (hip or knee) joint infections. The medical charts of all patients with surgical revisions for S. aureus hip or knee prosthetic joint infections (PJIs) who were given doxycycline-based SAT because of a high risk of failure of various origins were reviewed. Data regarding tolerability and effectiveness of doxycycline-based SAT were analysed. A total of 39 patients (mean age 66.1 ± 16.3 years) received doxycycline-base SAT in the period from January 2006 to January 2014. PJIs involved the hip in 23 patients (59.0%) and the knee in 16 (41.0%), and were qualified as early in 15 patients (38.5%). Methicillin-resistant S. aureus (MRSA) accounted for 22% of the total number of bacterial strains identified. All patients included in the study had surgery, which consisted of debridement and implant retention in 32 (82.1%). Adverse events likely attributable to SAT were reported in six patients (15.4%), leading to discontinuation of SAT in three (7.7%). A total of 29 patients (74.4%) remained event-free and 10 (25.6%) failed, including 8 (20.5%) relapses and 2 (5.1%) superinfections. Overall, 8 of the 10 failure cases were related to a doxycycline-susceptible pathogen. These results suggest that oral doxycycline used as SAT in patients treated for S. aureus hip or knee PJIs has an acceptable tolerability and effectiveness and appears to be a reasonable option in this setting.

Counter-intuitive plasma vitamin D and zinc status in HIV-1-infected adults with persistent low-level viraemia after treatment initiation: a pilot case-control study.

Determinants of persistent low-level viraemia [PLLV, a viral load (VL) of between 50 and 500 copies/mL] have not been elucidated. In a case-control study, we evaluated the influence of micronutrients on PLLV in a population of 454 HIV-1 adults having initiated antiretroviral therapy (ART) between January 2007 and December 2011. Plasma levels of retinol (vitamin A), 25-OH vitamin D2 + D3, vitamin E and zinc were measured at ART initiation in cases (PLLV after 6 months of ART) and in controls (VL <50 copies/mL after 6 months). Cases and controls were matched for the CD4 cell count (±50/mm3) and ethnic origin. Intergroup differences in demographic, biological and treatment parameters and sunshine intensity at ART initiation were adjusted using a propensity score. A receiver operating characteristic (ROC) curve was used to assess intergroup differences in plasma micronutrient levels. Thirty-three of the 454 patients (7.3%) displayed PLLV (median VL: 92 copies/mL). Patients were predominantly male (89%), Caucasian (64%) and CDC stage C (25%). The median age was 38 years, the median initial VL was 5.2 log10 copies/mL and the median CD4 count was 74/mm3. The 22 cases and matched controls were balanced in these respects, and had similar vitamin A/E levels. Two cases (9%) and 9 controls (41%) had a vitamin D level <10.3 ng/mL (p = 0.0015), and 2 cases (9%) and 10 controls (48%) had a zinc level <74.6 µg/dL (p = 0.04). Our results support in vitro studies suggesting that vitamin D favours HIV-1 replication and that HIV-1 is zinc-dependent. Wide-scale, prospective studies are required.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection.

OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

Outcome of patients with streptococcal prosthetic joint infections with special reference to rifampicin combinations.

BACKGROUND: Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known. METHODS: We performed a retrospective multicenter cohort study that involved patients with total hip/knee prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009. RESULTS: Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04). CONCLUSIONS: The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients.