Efficacy of single antibiotic therapy versus antibiotic combination in implant-free staphylococcal post-surgical spinal infections: a retrospective observational study.

BACKGROUND: Post-surgical spinal infections (pSSIs) are a serious complication of spinal surgeries, with Staphylococcus spp. being one of the most prominent bacteria identified. Optimal antimicrobial therapy for staphylococcal spinal infections without spinal implants is not well documented. METHODS: This single center retrospective 7-year observational study described and compared the outcome (treatment failure or mortality rate one year after diagnosis) of 20 patients with staphylococcal-implant-free pSSI treated with single or combination antibiotics. RESULTS: Median duration of treatment was 40 days (IQR 38-42), with 6 days (IQR 5-7) on intravenous antibiotics and 34 days (IQR 30-36) on oral therapy. Four patients (20%) underwent new surgical debridement, all due to surgical failure, and 1 patient died within the first year without significant differences between both treatment group. CONCLUSION: This study raises the possibility of single antibiotic therapy for patients with implant-free post-surgical spinal infections due to Staphylococcus spp.

Frequency and factors associated with infusion-related local complications of vancomycin on peripheral venous catheters.

BACKGROUND: Vancomycin is a reference antibiotic against methicillin-resistant staphylococci. Its administration is associated with infusion-related local complications (IRLC). To reduce this risk, it has been proposed to increase vancomycin dilution in the IV bag and to perform continuous infusion using the volumetric pump. The aim of our study was to assess the safety of peripheral infusion of vancomycin with the volumetric pump. OBJECTIVES: To compare the frequency of IRLC between patients receiving vancomycin and those receiving ß-lactam (BL) antibiotics. Our secondary objective was to assess factors associated with the occurrence of IRLC. PATIENTS AND METHODS: We conducted a prospective observational study in a French tertiary hospital. Between February 2021 and November 2021, we included all patients receiving continuous infusions of vancomycin or BL through a peripherally inserted venous catheter (PIVC). The primary endpoint was the occurrence of IRLC on Day 1 (D1). RESULTS: We included 168 patients (56 vancomycin, 112 BL). At D1, 14 patients (25%) presented IRLC in the vancomycin group versus 11 patients (10%) in the BL group (P = 0.01). There was significantly more IRLC in the group receiving vancomycin at an infused concentration above 5 mg/mL than those receiving BL (8/15, 53.3% versus 11/112, 10%, respectively, P < 0.01). However, no significant difference was observed between patients receiving infused vancomycin concentration ≤5 mg/mL and patients receiving BL (P = 0.4). CONCLUSION: Our data support safe administration of vancomycin if infused at a concentration under 5 mg/mL, through the volumetric pump on PIVC.

Evaluating the heart valve tissue diffusion of amoxicillin in infective endocarditis: a pilot prospective observational non-comparative study.

OBJECTIVES: Treating patients with infective endocarditis (IE) due to streptococci and enterococci currently involves high-dosage antibiotics. Recent literature suggests a 30%-70% diffusion rate could be extrapolated to human heart valve tissue. The objective of this study was to evaluate the diffusion coefficient of amoxicillin in heart valve tissue of patients operated for IE. METHODS: Adult patients were prospectively included that underwent surgery at the European Hospital Georges Pompidou for IE due to streptococci and enterococci and had previous IV amoxicillin treatment. Plasma (taken 48 h preoperatively) and heart valve tissue amoxicillin concentrations were measured with a validated LC-MS/MS method. The MIC values of amoxicillin were measured for all available isolates. RESULTS: Seventeen patients were included. Eleven (64.7%) patients had native valve IE and six (35.3%) had prosthetic valve IE. Fourteen IE cases (82.4%) were due to streptococci, one (5.9%) was due to enterococci and two (11.8%) were Haemophilus spp, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae group infections. Median (IQR) amoxicillin dose administered was 10.5 (8.0-12.0) g/day corresponding to 138.2 (112.5-160.0) mg/kg/day. The median amoxicillin plasma concentrations pre-surgery and intra-tissular weighted concentrations were 31.9 (25.9-51.9) mg/L and 19.0 (7.9-31.4) µg/g, respectively. Median tissue/plasma concentration ratio was 0.47 (0.24-0.67), with a median amoxicillin plasma/MIC ratio of 487 (179-745), and median amoxicillin tissue/MIC ratio of 42 (14-116). CONCLUSIONS: With a significant diffusion coefficient, amoxicillin dosage in heart valve tissues showed a concentration/MIC ratio well above current recommendations for bactericidal activity. Our study suggests that lower doses can be considered for susceptible bacteria.

TIVAP-related infection due to Gram-negative aerobic bacilli: should TIVAP stay or should it go?

We aimed to describe the outcome of totally implantable venous-access port (TIVAP)-related infections due to Gram-negative aerobic bacilli (Pseudomonas aeruginosa and other Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas maltophilia), or GNAB, and assess the safety of conservative treatment. We conducted a retrospective study in a French teaching hospital, from January 2016 to December 2020, including adult patients treated for TIVAP-related infection due to GNAB. Success of conservative treatment was defined as a functional TIVAP 3 months after infection with no recurrence. We performed a bivariate analysis and analyzed causes for treatment failure. We included 68 patients (53 TIVAP-related bloodstream infections, 11 TIVAP-related infections, and 4 probable TIVAP-related infections) due to GNAB, mostly P. aeruginosa (50/68, 74%). TIVAP removal was initially decided for 49/68 patients (72%). Among the 19/68 (28%) patients with conservative treatment (all for infections caused by P. aeruginosa), 5/19 (26%) had successful treatment, 7/19 (37%) experienced failure (without sepsis or septic shock), 6/19 (32%) died within 3 months without TIVAP removal and no signs of infection recurrence, and 1 patient had TIVAP removal as it was no longer required. TIVAP-related infections caused by GNAB frequently require TIVAP removal. Conservative treatment can be performed in selected patients with a non-complicated infection caused by P. aeruginosa, who can benefit from the continuation of antineoplastic chemotherapy or palliative care. Treatment failures were not associated with sepsis or septic shock.

Mycobacterium bovis infection of an aortobifemoral bypass graft with Streptococcus intermedius superinfection after intravesical bacillus Calmette-Guérin immunotherapy for bladder cancer.

BACKGROUND: The Bacillus Calmette-Guerin (BCG) is a life-attenuated form of Mycobacterium bovis widely used as immunotherapy for localized bladder cancer. Adverse reactions to intravesical BCG instillations are rare. CASE: We describe a 70-year-old man with a history of an aortobifemoral bypass graft, placement of a synthetic mesh for treatment of a ventral hernia and, most recently, superficial bladder cancer treated with BCG therapy. Ten months after his final intravesical BCG instillation, he complained of fever and asthenia. After 12 months of investigation, he was diagnosed with Mycobacterium bovis infection of his aortobifemoral bypass graft and abdominal mesh, with Streptococcus intermedius superinfection. The bypass graft was excised and replaced with an in situ arterial allograft, the abdominal mesh was removed, and treatment started with amoxicillin, isoniazid, rifampicin and ethambutol. Several additional vascular interventions were needed for allograft degradation, but 12 months after the final procedure, outcome was good. DISCUSSION AND CONCLUSIONS: Among 35 cases of mycotic aneurysm reported after BCG therapy in the last 10 years, only one involved a vascular prosthesis. Surgical repair of such aneurysms using prosthetic grafts is commonly performed, associated with anti-mycobacterial treatment. Prognosis is poor with mortality of 14% (4/35) and a 26% rate of aneurysm recurrence under treatment (9/35).

Late viral or bacterial respiratory infections in lung transplanted patients: impact on respiratory function.

BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; - 35 mL (IQR; - 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (- 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.

Prevalence and correlates of growth failure in young African patients with sickle cell disease.

Growth failure (GF) in children with sickle cell disease (SCD) tends to decline in high-income countries, but data are lacking in sub-Saharan Africa. We performed a cross-sectional study nested in the CADRE (Cœur, Artères et DREpanocytose) cohort in Mali, Senegal, Cameroon, Gabon and the Ivory Coast. SCD patients and healthy controls aged 5-21 years old were recruited (n = 2583). Frequency of GF, defined as a height, weight or body mass index below the 5th percentile on World health Organization growth charts, was calculated. We assessed associations between GF and SCD phenotypic group, clinical and biological characteristics and history of SCD-related complications. GF was diagnosed in 51% of HbSS, 58% of HbSß0 , 44% of HbSC, 38% of HbSß+ patients and 32% of controls. GF in patients was positively associated with parents' lower education level, male sex, age 12-14 years, lower blood pressure, HbSS or HbSß0 phenotypes, icterus, lower haemoglobin level, higher leucocyte count and microalbuminuria. No association was found between GF and clinical SCD-related complications. In sub-Saharan Africa, GF is still frequent in children with SCD, especially in males and during adolescence. GF is associated with haemolysis and microalbuminuria, but not with the history of SCD-related clinical complications.

Degree of anemia, indirect markers of hemolysis, and vascular complications of sickle cell disease in Africa.

The hyperhemolysis paradigm that describes overlapping "hyperhemolytic-endothelial dysfunction" and "high hemoglobin-hyperviscous" subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle ß-zero-thalassemia [Sß0], 495 SC, and 161 sickle ß+-thalassemia [Sß+]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sß0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sß0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

Infectious native aortic aneurysm with negative blood cultures: do not forget the pneumococcal urinary antigen test!

Infectious native aortic aneurysm (INAA) are rare but life-threatening infections. Early microbiological identification is crucial to initiate adequate therapy and decrease the peri-operative risk, but can be challenging when blood cultures remain negative. We describe two cases of pneumococcal INAA with negative blood cultures, diagnosed in the with the pneumococcal urinary antigen test.

Amikacin pharmacokinetic/pharmacodynamic in intensive care unit: a prospective database.

BACKGROUND: Aminoglycosides have a concentration-dependent therapeutic effect when peak serum concentration (Cmax) reaches eight to tenfold the minimal inhibitory concentration (MIC). With an amikacin MIC of 8 mg/L, the Cmax should be 64-80 mg/L. This objective is based on clinical breakpoints and not on measured MIC. This study aimed to assess the proportion of patients achieving the pharmacokinetic/pharmacodynamic (PK/PD) target Cmax/MIC ≥ 8 using the measured MIC in critically ill patients treated for documented Gram-negative bacilli (GNB) infections. METHODS: Retrospective analysis from February 2016 to December 2017 of a prospective database conducted in 2 intensive care units (ICU). All patients with documented severe GNB infections treated with amikacin (single daily dose of 25 mg/kg of total body weight (TBW)) with both MIC and Cmax measurements at first day of treatment (D1) were included. Results are expressed in n (%) or median [min-max]. RESULTS: 93 patients with 98 GNB-documented infections were included. The median Cmax was 55.2 mg/L [12.2-165.7] and the median MIC was 2 mg/L [0.19-16]. Cmax/MIC ratio ≥ 8 was achieved in 87 patients (88.8%) while a Cmax ≥ 64 mg/L was achieved in only 38 patients (38.7%). Overall probability of PK/PD target attainment was 93%. No correlation was found between Cmax/MIC ratio and clinical outcome at D8 and D28. CONCLUSION: According to PK/PD parameters observed in our study, single daily dose of amikacin 25 mg/kg of TBW appears to be sufficient in most critically ill patients treated for severe GNB infections.

Bacterial and viral co-infections in patients with severe SARS-CoV-2 pneumonia admitted to a French ICU.

BACKGROUND: Data on the prevalence of bacterial and viral co-infections among patients admitted to the ICU for acute respiratory failure related to SARS-CoV-2 pneumonia are lacking. We aimed to assess the rate of bacterial and viral co-infections, as well as to report the most common micro-organisms involved in patients admitted to the ICU for severe SARS-CoV-2 pneumonia. PATIENTS AND METHODS: In this monocenter retrospective study, we reviewed all the respiratory microbiological investigations performed within the first 48 h of ICU admission of COVID-19 patients (RT-PCR positive for SARS-CoV-2) admitted for acute respiratory failure. RESULTS: From March 13th to April 16th 2020, a total of 92 adult patients (median age: 61 years, 1st-3rd quartiles [55-70]; males: n = 73/92, 79%; baseline SOFA: 4 [3-7] and SAPS II: 31 [21-40]; invasive mechanical ventilation: n = 83/92, 90%; ICU mortality: n = 45/92, 49%) were admitted to our 40-bed ICU for acute respiratory failure due to SARS-CoV-2 pneumonia. Among them, 26 (28%) were considered as co-infected with a pathogenic bacterium at ICU admission with no co-infection related to atypical bacteria or viruses. The distribution of the 32 bacteria isolated from culture and/or respiratory PCRs was as follows: methicillin-sensitive Staphylococcus aureus (n = 10/32, 31%), Haemophilus influenzae (n = 7/32, 22%), Streptococcus pneumoniae (n = 6/32, 19%), Enterobacteriaceae (n = 5/32, 16%), Pseudomonas aeruginosa (n = 2/32, 6%), Moraxella catarrhalis (n = 1/32, 3%) and Acinetobacter baumannii (n = 1/32, 3%). Among the 24 pathogenic bacteria isolated from culture, 2 (8%) and 5 (21%) were resistant to 3rd generation cephalosporin and to amoxicillin-clavulanate combination, respectively. CONCLUSIONS: We report on a 28% rate of bacterial co-infection at ICU admission of patients with severe SARSCoV-2 pneumonia, mostly related to Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Enterobacteriaceae. In French patients with confirmed severe SARSCoV-2 pneumonia requiring ICU admission, our results encourage the systematic administration of an empiric antibiotic monotherapy with a 3rd generation cephalosporin, with a prompt de-escalation as soon as possible. Further larger studies are needed to assess the real prevalence and the predictors of co-infection together with its prognostic impact on critically ill patients with severe SARS-CoV-2 pneumonia.

Case report study of the first five COVID-19 patients treated with remdesivir in France.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the virus responsible for the coronavirus disease 2019 (COVID-19) outbreak worldwide. Data on treatment are scare and parallels have been made between SARS-CoV-2 and other coronaviruses. Remdesivir is a broad-spectrum antiviral with efficient in vitro activity against SARS-CoV-2. Evidence of clinical improvement in patients with severe COVID-19 treated with remdesivir is controversial. The aim of this study was to describe the clinical outcomes and virological monitoring of the first five COVID-19 patients admitted to the intensive care unit of Bichat-Claude Bernard University Hospital, Paris, France, for severe pneumonia related to SARS-CoV-2 and treated with remdesivir. Quantitative reverse transcription PCR was used to monitor SARS-CoV-2 in blood plasma and the lower and upper respiratory tract. Among the five patients treated, two needed mechanical ventilation and one needed high-flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load in the upper respiratory tract was observed in most cases, but two patients died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted before the initialy planned duration in four patients, two because of alanine aminotransferase elevations (3 to 5 normal range) and two because of renal failure requiring renal replacement. This case series of five COVID-19 patients requiring intensive care unit treatment for respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.

Clinical features and outcome of patients with acute respiratory failure revealing anti-synthetase or anti-MDA-5 dermato-pulmonary syndrome: a French multicenter retrospective study.

BACKGROUND: Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease. We undertook a 13-year retrospective multicenter study in 35 French ICUs in order to describe the clinical presentation and the outcome of patients admitted to the ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes. RESULTS: From 2005 to 2017, 47 patients (23 males; median age 60 [1st-3rd quartiles 52-69] years, no comorbidity 85%) were admitted to the ICU for ARF revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes. Muscular, articular and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%) patients, respectively. Seventeen of them (36%) had no extra-pulmonary manifestations. C-reactive protein was increased (139 [40-208] mg/L), whereas procalcitonine was not (0.30 [0.12-0.56] ng/mL). Proportion of patients with creatine kinase ≥ 2N was 20% (n = 9/47). Forty-two patients (89%) had ARDS, which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal membrane oxygenation requirement. Proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively. ICU and hospital mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively. Patients with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001). CONCLUSIONS: Intensivists should consider inflammatory myopathies as a cause of ARF of unknown origin. Extra-pulmonary manifestations are commonly lacking. Mortality is high, especially in aMDA-5 dermato-pulmonary syndrome.

Sternal Wound Infection after Cardiac Surgery: Management and Outcome.

BACKGROUND: Sternal Wound Infection (SWI) is a severe complication after cardiac surgery. Debridement associated with primary closure using Redon drains (RD) is an effective treatment, but data on RD management and antibiotic treatment are scarce. METHODS: We performed a single-center analysis of consecutive patients who were re-operated for SWI between 01/2009 and 12/2012. All patients underwent a closed drainage with RD (CDRD). Patients with endocarditis or those who died within the first 45 days were excluded from management analysis. RD fluid was cultured twice weekly. Variables recorded were clinical and biological data at SWI diagnosis, severity of SWI based on criteria for mediastinitis as defined by the Centers for Disease Control (CDC), antibiotic therapy, RD management and patient's outcome. RESULTS: 160 patients developed SWI, 102 (64%) fulfilled CDC criteria (CDC+) and 58 (36%) did not (CDC- SWI). Initial antibiotic treatment and surgical management were similar in CDC+ and CDC- SWI. Patients with CDC+ SWI had a longer duration of antibiotic therapy and a mortality rate of 17% as compared to 3% in patients with CDC- SWI (p = 0.025). Rates of superinfection (10% and 9%) and need for second reoperation (12% and 17%) were similar. Failure (death or need for another reoperation) was associated with female gender, higher EuroScore for prediction of operative mortality, and stay in the ICU. CONCLUSION: In patients with SWI, initial one-stage surgical debridement with CDRD is associated with favorable outcomes. CDC+ and CDC- SWI received essentially the same management, but CDC+ SWI has a more severe outcome.

Rapidly progressive kidney failure induced by fungal mycelia obstructing indwelling ureteral stents.

Antibiotics reduce the commensal flora in the gut, thereby facilitating the overgrowth of undesirable microorganisms such as Candida albicans. Here, we report the case of a 48-year-old woman with a history of obstructive uropathy consecutive to a radiation therapy, in whom both indwelling ureteral stents were rapidly occluded by fungal mycelia, resulting in a rapidly progressive kidney failure. Ascendant infection by C albicans had occurred after a 2- week course of antibiotics, prescribed for a perforative peritonitis also due to radiation-induced colitis. As shown by iterative CT scans made before (at the time of the diagnosis of peritonitis) and after the antibiotic course, kidney failure was explained by a sudden and bilateral pyelocaliceal dilation, due to the obstruction of the ureteral stents. Fungal mycelia were objectivised during the replacement procedure. Intravenous fluconazole was started, and renal function recovered ad integrum with the relief of the obstruction.