Probabilistic chemotherapy in knee and hip replacement infection: the place of linezolid.

Prosthetic joint infection (PJI) can occur with a wide range of microorganisms and clinical features. After replacement surgery of prosthetic joint, prescription of probabilistic broad-spectrum antimicrobial therapy is usual, while awaiting microbial culture results. The aim of our study was to describe the antibiotic susceptibility of microorganisms isolated from hip and knee PJI. The data were collected to determine the best alternative to the usual combination of piperacillin-tazobactam (TZP) or cefotaxime (CTX) and vancomycin (VAN). Based on a French prospective, multicenter study, we analyzed microbiological susceptibility to antibiotics of 183 strains isolated from patients with confirmed hip or knee PJI. In vitro susceptibility was evaluated: TZP+VAN, TZP+linezolid (LZD), CTX+VAN, and CTX+LZD. We also analyzed resistance to different antibiotics commonly used as oral alternatives. Among the 183 patients with PJI, 62 (34%) had a total knee prosthesis, and 121 (66%) a hip prosthesis. The main identified bacteria were Staphylococcus aureus (32.2% of isolates), coagulase-negative staphylococci (27.3%), Enterobacteriaceae (14.2%), and Streptococcus (13.7%). Infections were polymicrobial for 28 (15.3%) patients. All combinations were highly effective: CTX+VAN, CTX+LZD, TZP+VAN, and TZP+LZD (93.4%, 94%, 98.4%, and 98.9% of all cases respectively). Use of LZD instead of VAN in combination with a broad-spectrum beta-lactam covers almost all of the bacteria isolated in PJI. This association should be considered in probabilistic chemotherapy, as it is particularly easy to use (oral administration and no vancomycin monitoring).

Disseminated Spiroplasma apis Infection in Patient with Agammaglobulinemia, France.

We report a disseminated infection caused by Spiroplasma apis, a honeybee pathogen, in a patient in France who had X-linked agammaglobulinemia. Identification was challenging because initial bacterial cultures and direct examination by Gram staining were negative. Unexplained sepsis in patients with agammaglobulinemia warrants specific investigation to identify fastidious bacteria such as Spiroplasma spp.

Histopathological Diagnosis of Prosthetic Joint Infection: Does a Threshold of 23 Neutrophils Do Better than Classification of the Periprosthetic Membrane in a Prospective Multicenter Study?

No gold standard exists for histopathological diagnosis of a prosthetic joint infection (PJI). The historical criterion considers the presence of neutrophil infiltration upon examination of periprosthetic tissue. Morawietz et al. proposed a classification of periprosthetic membranes (Morawietz et al., Clin Pathol 59:591-597, 2006, https://doi.org/10.1136/jcp.2005.027458) and a more recently described classification with a new cutoff value of 23 neutrophils in 10 high-power fields (Morawietz et al., Histopathology 54:847-853, 2009. https://doi.org/10.1111/j.1365-2559.2009.03313.x). We performed a multicenter prospective study, which compared both methods for the diagnosis of PJI. All suspicions of PJI (n = 264) between December 2010 and March 2012 in seven centers were prospectively included. Five perioperative specimens were collected per patient for cultures, and one was collected for histology. Diagnosis of PJI was made according to the Infectious Diseases Society of America (IDSA) guidelines. Histopathological analysis classified the patients according to the threshold of 23 neutrophils and according to the classification of Morawietz. Performances of both methods were compared by using clinical and/or bacteriological criteria as the gold standard. Among 264 patients with suspected PJI, a diagnosis of infection was confirmed in 215 and unconfirmed in 49 patients. Histopathological analysis was available for 150 confirmed PJI and 40 unconfirmed PJI cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 78.7%, 90.0%, 96.7%, 52.9%, and 81.1%, respectively, for the Morawietz classification, and 82.0%, 90.0%, 96.9%, 57.1%, and 83.7%, respectively, for the 23-neutrophil threshold. The new algorithm using a threshold of 23 neutrophils can be proposed as a new gold standard for the histopathological diagnosis of PJI.

How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study.

Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI.

Risk Factors and Outcomes for Intestinal Carriage of AmpC-Hyperproducing Enterobacteriaceae in Intensive Care Unit Patients.

In a cohort of 1,209 intensive care unit (ICU) patients, the prevalence of intestinal colonization with high-level expressed AmpC cephalosporinase-producing Enterobacteriaceae (HLAC-PE) rose steadily from 2% at admission to 30% in patients with lengths of stay (LOS) exceeding 4 weeks. In multivariate analysis, LOS was the main predictor of carriage acquisition after adjustment on antimicrobial exposure. HLAC-PE infection occurred in 15% of carriers. Carriage and infection were associated with a marked increase in carbapenem consumption.

First experience of a multicenter external quality assessment of molecular 16S rRNA gene detection in bone and joint infections.

The objective of this study was to assess the performance of seven French laboratories for 16S rRNA gene detection by real-time PCR in the diagnosis of bone and joint infection (BJI) to validate a large multicenter study. External quality control (QC) was required owing to the differences in extraction procedures and the molecular equipment used in the different laboratories. Three proficiency sets were organized, including four bacterial DNA extracts and four bead mill-pretreated osteoarticular specimens. Extraction volumes, 16S rRNA gene primers, and sequencing interpretation rules were standardized. In order to assess each laboratory's ability to achieve the best results, scores were assigned, and each QC series was classified as optimal, acceptable, or to be improved. A total of 168 QCs were sent, and 160 responses were analyzed. The expected results were obtained for 93.8%, with the same proportion for extracts (75/80) and clinical specimens (75/80). For the specimens, there was no significant difference between manual and automated extraction. This QC demonstrated the ability to achieve good and homogeneous results using the same 16S rRNA gene PCR with different equipment and validates the possibility of high-quality multicenter studies using molecular diagnosis for BJI.

Evaluation of 16S rRNA gene PCR sensitivity and specificity for diagnosis of prosthetic joint infection: a prospective multicenter cross-sectional study.

There is no standard method for the diagnosis of prosthetic joint infection (PJI). The contribution of 16S rRNA gene PCR sequencing on a routine basis remains to be defined. We performed a prospective multicenter study to assess the contributions of 16S rRNA gene assays in PJI diagnosis. Over a 2-year period, all patients suspected to have PJIs and a few uninfected patients undergoing primary arthroplasty (control group) were included. Five perioperative samples per patient were collected for culture and 16S rRNA gene PCR sequencing and one for histological examination. Three multicenter quality control assays were performed with both DNA extracts and crushed samples. The diagnosis of PJI was based on clinical, bacteriological, and histological criteria, according to Infectious Diseases Society of America guidelines. A molecular diagnosis was modeled on the bacteriological criterion (≥ 1 positive sample for strict pathogens and ≥ 2 for commensal skin flora). Molecular data were analyzed according to the diagnosis of PJI. Between December 2010 and March 2012, 264 suspected cases of PJI and 35 control cases were included. PJI was confirmed in 215/264 suspected cases, 192 (89%) with a bacteriological criterion. The PJIs were monomicrobial (163 cases [85%]; staphylococci, n = 108; streptococci, n = 22; Gram-negative bacilli, n = 16; anaerobes, n = 13; others, n = 4) or polymicrobial (29 cases [15%]). The molecular diagnosis was positive in 151/215 confirmed cases of PJI (143 cases with bacteriological PJI documentation and 8 treated cases without bacteriological documentation) and in 2/49 cases without confirmed PJI (sensitivity, 73.3%; specificity, 95.5%). The 16S rRNA gene PCR assay showed a lack of sensitivity in the diagnosis of PJI on a multicenter routine basis.

Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000-2011.

BACKGROUND: Chloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system. METHODS: The study was conducted by the Malaria National Reference Centre, France. The database collated the pfcrtK76T molecular marker for CQ susceptibility and the in vitro response to CQ of parasites from travellers' isolates returning from Senegal, Mali, Ivory Coast or Cameroon. As a proxy of drug pressure, data regarding CQ intake in febrile children were collated for the study period. Logistic regression models were used to detect trends in the proportions of CQ resistant isolates. RESULTS: A total of 2874 parasite isolates were genotyped between 2000-2011. The prevalence of the pfcrt76T mutant genotype significantly decreased for Senegal (from 78% to 47%), Ivory Coast (from 63% to 37%), Cameroon (from 90% to 59%) and remained stable for Mali. The geometric mean of the 50% inhibitory concentration (IC50) of CQ in vitro susceptibility and the proportion of resistant isolates (defining resistance as an IC50 value > 100 nM) significantly decreased for Senegal (from 86 nM (59%) to 39 nM (25%)), Mali (from 84 nM (50%) to 51 nM (31%)), Ivory Coast (from 75 nM (59%) to 29 nM (16%)) and Cameroon (from 181 nM (75%) to 51 nM (37%)). Both analyses (molecular and in vitro susceptibility) were performed for the 2004-2011 period, after the four countries had officially discontinued CQ and showed an accelerated decline of the resistant isolates for the four countries. Meanwhile, CQ use among children significantly deceased in this region (fixed effects slope = -0.3, p < 10-3). CONCLUSIONS: An increase in CQ susceptibility following official withdrawal of the drug was observed in travellers returning from West and Central African countries. The same trends were observed for molecular and in vitro analysis between 2004-2011 and they correlated to the decrease of the drug pressure.

Case Report: Co-infection with SARS-CoV-2 and influenza H1N1 in a patient with acute respiratory distress syndrome and a pulmonary sarcoidosis.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has been a global public health concern. Co-infection of SARS-CoV-2 and other respiratory syndrome has been rarely reported. We report coinfection of SARS-CoV-2 and 2009 H1N1 Influenza strain in a French patient with pneumonia leading to acute respiratory distress syndrome.  The patient also had a medical history of pulmonary sarcoidosis with a restrictive ventilatory syndrome, which would be a supplementary risk to develop a poor outcomes. This case highlights the possible coinfection of two severe SARS-CoV-2 and influenza H1N1 viruses, which presents a higher risk to extend the care duration. The overlapping clinical features of the two respiratory syndromes is a challenge, and awareness is required to recommend an early differential diagnosis.

CTX-M beta-lactamase production and virulence of Escherichia coli K1.

We report a patient with neonatal meningitis caused by a CTX-M-1-producing Escherichia coli K1 strain. The influence of CTX-M production on virulence was investigated in cell culture and a newborn mouse model of meningitis. CTX-M production had no influence on virulence but was a major factor in clinical outcome.

The Right Time to Safely Re-Evaluate Empirical Antimicrobial Treatment of Hip or Knee Prosthetic Joint Infections.

Currently, no guideline provides recommendations on the duration of empirical antimicrobial treatment (EAT) in prosthetic joint infection (PJI). The aim of our study was to describe the time to growth of bacteria involved in PJI, rendering possible decreased duration of EAT. Based on a French multicentre prospective cohort study, culture data from patients with confirmed hip or knee PJI were analysed. For each patient, five samples were processed. Time to positivity was defined as the first positive medium in at least one sample for virulent pathogens and as the first positive medium in at least two samples for commensals. Definitive diagnosis of polymicrobial infections was considered the day the last bacteria were identified. Among the 183 PJIs, including 28 polymicrobial infections, microbiological diagnosis was carried out between Day 1 (D1) and D5 for 96.7% of cases. There was no difference in the average time to positivity between acute and chronic PJI (p = 0.8871). Microbiological diagnosis was given earlier for monomicrobial than for polymicrobial infections (p = 0.0034). When an optimized culture of peroperative samples was carried out, almost all cases of PJI were diagnosed within five days, including polymicrobial infections. EAT can be re-evaluated at D5 according to microbiological documentation.

Antibiotic resistance and virulence properties of Pseudomonas aeruginosa strains from mechanically ventilated patients with pneumonia in intensive care units: comparison with imipenem-resistant extra-respiratory tract isolates from uninfected patients.

We investigated the epidemiology of antibiotic resistance and virulence properties among Pseudomonas aeruginosa clinical isolates collected in 1999 from patients hospitalized in the intensive care units of the centre hospitalier d'Orléans, in France. We compared the totality of the strains from mechanically ventilated patients with pneumonia (33 non-duplicate isolates, group 1) to 15 randomly chosen, imipenem-resistant, extra-respiratory tract isolates, collected from non-infected patients hospitalized in the same units (group 2). The isolates were serotyped, typed by random amplified polymorphic DNA (RAPD), and screened for their pneumocyte cell adherence, cytotoxicity, and antibiotic resistance. A total of 35 RAPD profiles were found, and only two profiles were encountered in both groups, demonstrating a high genetic diversity. 84.8% of the group 1 and 93.3% of the group 2 isolates adhered to A549 cells. Three non-exclusive adhesive patterns were observed: a diffuse adhesion in 38 isolates, a localized adhesion in 14 isolates, and an aggregative adhesion in seven isolates. 78.8% of the group 1 and 93.3% of the group 2 isolates were cytotoxic. Considering all 48 isolates, there was a strong and statistically significant correlation between cytotoxicity and adherence. Among the three dominant serotypes, O:12 isolates were in majority avirulent, but the great majority of O:1 and all the O:11 isolates were found adherent and cytotoxic. Gentamicin was the least active antibiotic for both groups, and ceftazidime was the most active antibiotic for group 1 and amikacin for group 2. The penicillinase production phenotype was significantly correlated with a decrease in P. aeruginosa virulence.

Orthopaedic-implant infections by Escherichia coli: molecular and phenotypic analysis of the causative strains.

OBJECTIVES: Little is known about Escherichia coli Orthopaedic Implant Infections (OII) pathogenesis. Thus, we compared 30 clinical strains isolated in this context with 30 clinical strains of faecal origin, in order to identify phenotypic and genetic features related to E. coli OII. METHODS: Phylogenetic analysis and detection of 19 virulence genes were performed by PCR. Ability to form biofilm was studied using the crystal violet reference method and the innovative BioFilm Ring Test(®). RESULTS: Most of the OII isolates (56.7%) belonged to the virulence-associated phylogenetic group B2, but did not present a specific set of virulence factors. S fimbriae was the only adhesin significantly associated with OII isolates. Isolates varied greatly in their ability to form biofilm but OII isolates did not produce significantly more biofilm in vitro than isolates of faecal origin, whatever the method used. CONCLUSIONS: Neither a specific pathogenic signature nor an increased ability to form biofilm in vitro was detected in E. coli strains isolated from OII. Nevertheless, genetic properties of these isolates could provide a clue to their origin. Hence, we found that virulence factors of uropathogenic strains and urological disorders were frequently detected among our OII cohort.

Bone infection in cat-scratch disease: a review of the literature.

OBJECTIVE: To describe the main features of bone infection associated with Cat-scratch disease (CSD). METHODS: We searched for articles indexed in the international literature databases by using the following key words: "Bartonella", "bone", "cat-scratch", "osteomyelitis" and "osteolytic". RESULTS: Cases of 47 patients were reviewed. The median age was 9 years, with an equal sex distribution. Bone pain and fever were the main symptoms. The presence of fever and increased age were more common in patients with bone infection than classically reported in uncomplicated (i.e. nodal) CSD. The vertebral column and pelvic girdle were the most common sites of infection. Radiological examination typically confirmed bone osteolysis. All patients recovered without complications or chronic infection, although they received a various combination antibiotic regimen and duration therapy. The mechanism by which infection might spread to the bone is via the haematogenous route, accounting for most of the disseminated cases and via the lymphatic route, for those with regional limited extension. CONCLUSIONS: Bone infection is rare but should be considered when bone pain and fever are present in a patient with nodal CSD. The prognosis is good, whatever treatment is given. Thus bone biopsy should be recommended only in a difficult diagnostic setting, when other bacteria or malignant disease are suspected.

Effect of ceftazidime, amikacin and ciprofloxacin on biofilm formation by some enterobacterial clinical isolates.

The effect of sub-minimal inhibitory concentrations of antimicrobial agents on the biofilm formationto polystyrene by Escherichia coli, Proteus vulgaris, Providencia stuartii, and Morganella morganii was investigated by examining eight clinical strains. All the isolates tested were efficient biofilm-forming strains in the microtiter plate assay, with crystal violet staining (OD595 nm) ranging from 0.13 +/- 0.01 for P. stuartii ER21870 to 1.23 +/- 0.02 for P. vulgaris ER50120. The biofilm formation of the majority of the strains was affected in the presence of ceftazidime or ciprofloxacin: biofilm formation significantly decreased for all the E. coli and P. vulgaris strains in the presence of either of the two antibiotics, it also decreased for M. morganii ER89472 in the presence of ceftazidime but increased for P. stuartii ER21870 and M. morganii ER89472 in the presence of ciprofloxacin. Amikacin decreased only the biofilm formation of P. stuartii ER08274. In addition to their antibacterial activity, ceftazidime and ciprofloxacin could be effective in preventing the biofilm formation of E. coli and P. vulgaris.

Aortic prosthetic endocarditis with Neisseria elongata subspecies nitroreducens.

A case of Neisseria elongata subsp. nitroreducens endocarditis with a favourable course is presented. Dental foci were involved as the infective origin. Only conservative therapy was performed for 6 weeks; no complications were registered in 3 months of follow-up. The other 12 cases with similar aetiology communicated in the past 30 y were reviewed.