Can we rely on histopathological results for the diagnosis of prosthetic joint infection?

BACKGROUND: Histopathology is one of the diagnostic criteria for prosthetic joint infection (PJI) proposed by all academic societies. The aim of this study was to compare histopathological and microbiological results from samples taken intraoperatively at the same site in patients with suspected or proven PJI. PATIENTS AND METHODS: We conducted a monocenter retrospective study including all patients having undergone surgery from 2007 to 2015 with suspected or proven PJI. During surgery, both histopathological and microbiological samples were taken. Patients with a history of antimicrobial treatment 2 weeks prior to surgery were excluded. We considered as major criteria and gold standard for PJI diagnosis the presence of a sinus tract communication and/or the same microorganism in at least two cultures. RESULTS: Finally, 181 patients who underwent 309 surgeries were included. The median number of samples per surgery was 4 (interquartile range (IQR) = 3-5) for histopathology and 5 (IQR = 4-6) for microbiology. Major criteria were observed in 177 patients (57.3%), while positive histology in at least one intraoperative sample was present in 119 (38.5%). The concordance was 74%. The sensitivity and specificity of histopathology were 61% and 92% respectively. Available "histopathology-culture" sample pairs numbered 1247. Among them, positive histopathology was found in 292 samples (23%) and culture in 563 (45%). Concordance was 64%. The highest correlation was observed for very early infection (<1 month) (OR: 9.1, 95% CI: 3.6-23) and for virulent microorganisms, such as Staphylococcus aureus (OR: 7.8, 95% CI: 5.2-11.8), Streptococci (OR:7.8; 95% CI: 4-15.2) or Enterobacterales (OR: 7.4; 95% CI: 4.2-13.1). CONCLUSION: Histopathologic examination is a valuable criterion for PJI diagnosis, but it may lack sensitivity for chronic infections or due to low-virulence pathogens.

Characteristics of Enterobacter cloacae prosthetic joint infections.

OBJECTIVES: Enterobacter cloacae prosthetic joint infections (PJI) are rare and poorly documented. PATIENTS AND METHODS: We conducted a retrospective and monocentric study in an orthopedic unit supporting complex bone and joint infections. Between 2012 and 2016 we collected background, clinical, biological, and microbiological data from 20 patients presenting with prosthetic joint infection and positive for E. cloacae, as well as data on their surgical and medical treatment and outcome. RESULTS: Infections were localized in the hip (n=14), knee (n=5), or ankle (n=1). The median time between arthroplasty and septic revision was three years. Fourteen patients (70%) had undergone at least two surgeries due to previous prosthetic joint infections. The median time between the last surgery and the revision for E. cloacae infection was 31 days. Eleven patients (55%) were infected with ESBL-producing strains. The most frequently used antibiotics were carbapenems (n=9), cefepime (n=7), quinolones (n=7), and fosfomycin (n=4). The infection was cured in 15 patients (78.9%) after a 24-month follow-up. Five patients had a recurrent infection with another microorganism and four patients had a relapse of E. cloacae infection. The global success rate was 52.7% (58.3% for DAIR and 75% for DAIR+ciprofloxacin). CONCLUSION: Prosthetic joint infections due to E. cloacae usually occur early after the last prosthetic surgery, typically in patients with complex surgical and medical histories. The success rate seems to be increased when DAIR is associated with ciprofloxacin.

Species and antimicrobial susceptibility testing of coagulase-negative staphylococci in periprosthetic joint infections.

The objective was to evaluate the distribution of coagulase-negative staphylococci (CNS) involved in periprosthetic-joint infections (PJIs) and to describe their susceptibility profile to antibiotics. We conducted a multicentre retrospective study in France, including 215 CNS PJIs between 2011 and 2015. CNS PJIs involved knees in 54% of the cases, hips in 39%, other sites in 7%. The distribution of the 215 strains was: Staphylococcus epidermidis 129 (60%), Staphylococcus capitis 24 (11%), Staphylococcus lugdunensis 21 (10%), Staphylococcus warneri 8 (4%), Staphylococcus hominis 7 (3%), Staphylococcus haemolyticus 7 (3%). More than half of the strains (52.1%) were resistant to methicillin, 40.9% to ofloxacin, 20% to rifampicin. The species most resistant to antibiotics were S. hominis, S. haemolyticus, S. epidermidis, with 69.7% of the strains resistant to methicillin and 30% simultaneously resistant to clindamycin, cotrimoxazole, ofloxacin and rifampicin. No strain was resistant to linezolid or daptomycin. In this study on CNS involved in PJIs, resistance to methicillin is greater than 50%. S. epidermidis is the most frequent and resistant species to antibiotics. Emerging species such S. lugdunensis, S. capitis and Staphylococcus caprae exhibit profiles more sensitive to antibiotics. The antibiotics most often active in vitro are linezolid and daptomycin.

Staphylococcus lugdunensis, a serious pathogen in periprosthetic joint infections: comparison to Staphylococcus aureus and Staphylococcus epidermidis.

OBJECTIVES: The aim of this study was to assess the characteristics of periprosthetic joint infection (PJI) due to Staphylococcus lugdunensis and to compare these to the characteristics of PJI due to Staphylococcus aureus and Staphylococcus epidermidis. METHODS: A retrospective multicentre study including all consecutive cases of S. lugdunensis PJI (2000-2014) was performed. Eighty-eight cases of staphylococcal PJI were recorded: 28 due to S. lugdunensis, 30 to S. aureus, and 30 to S. epidermidis, as identified by Vitek 2 or API Staph (bioMérieux). RESULTS: Clinical symptoms were more often reported in the S. lugdunensis group, and the median delay between surgery and infection was shorter for the S. lugdunensis group than for the S. aureus and S. epidermidis groups. Regarding antibiotic susceptibility, the S. lugdunensis strains were susceptible to antibiotics and 61% of the patients could be treated with levofloxacin + rifampicin. The outcome of the PJI was favourable for 89% of patients with S. lugdunensis, 83% with S. aureus, and 97% with S. epidermidis. CONCLUSION: S. lugdunensis is an emerging pathogen with a pathogenicity quite similar to that of S. aureus. This coagulase-negative Staphylococcus must be identified precisely in PJI, in order to select the appropriate surgical treatment and antibiotics .

[Pediatric brucellosis : A case report and literature review]. / Brucellose : revue de la littérature à propos d'un cas pédiatrique.

Brucellosis is an overlooked infection of widespread geographic distribution. This disease is rarely evoked when assessing unexplained pediatric fever, and only 20-30 cases (children and adults) are confirmed per year. Risk factors for contracting brucellosis are exposure to bodily fluids and consumption of unpasteurized dairy products from infected animals. Most cases of brucellosis are associated with traveling to or importing contaminated goods from endemic areas. Here, we report a case of brucellosis in a 16-month-old patient hospitalized for an acute febrile illness in a French general pediatric ward. An antibiotic regimen of rifampicin and co-trimoxazole given over 6 weeks led to successful cure without relapse. The child had eaten a cake made from unpasteurized goat's milk and imported from Oran, a region in Algeria. His mother had consumed the same cake and was hospitalized for brucellosis 15 days later. Clinicians should suspect brucellosis when encountering febrile patients who have traveled to endemic areas, been exposed to body fluids or products of abortion of farm animals, or consumed unpasteurized products.

Rapid Isolation of Staphylococcus aureus Pathogens from Infected Clinical Samples Using Magnetic Beads Coated with Fc-Mannose Binding Lectin.

Here we describe how Staphylococcus aureus bacteria can be rapidly isolated from clinical samples of articular fluid and synovial tissue using magnetic beads coated with the engineered chimeric human opsonin protein, Fc-mannose-binding lectin (FcMBL). The FcMBL-beads were used to capture and magnetically remove bacteria from purified cultures of 12 S. aureus strains, and from 8 articular fluid samples and 4 synovial tissue samples collected from patients with osteoarthritis or periprosthetic infections previously documented by positive S. aureus cultures. While the capture efficiency was high (85%) with purified S. aureus strains grown in vitro, direct FcMBL-bead capture from the clinical samples was initially disappointing (< 5% efficiency). Further analysis revealed that inhibition of FcMBL binding was due to coating of the bacteria by immunoglobulins and immune cells that masked FcMBL binding sites, and to the high viscosity of these complex biological samples. Importantly, capture of pathogens using the FcMBL-beads was increased to 76% efficiency by pretreating clinical specimens with hypotonic washes, hyaluronidase and a protease cocktail. Using this approach, S. aureus bacteria could be isolated from infected osteoarthritic tissues within 2 hours after sample collection. This FcMBL-enabled magnetic method for rapid capture and concentration of pathogens from clinical samples could be integrated upstream of current processes used in clinical microbiology laboratories to identify pathogens and perform antibiotic sensitivity testing when bacterial culture is not possible or before colonies can be detected.

Is Xpert MRSA/SA SSTI real-time PCR a reliable tool for fast detection of methicillin-resistant coagulase-negative staphylococci in periprosthetic joint infections?

Periprosthetic joint infections (PJIs) are frequently caused by methicillin-resistant coagulase-negative staphylococci (CoNS). Cultures remain the gold standard but often require a few days. Thus, a rapid test could be interesting to guide antibiotic strategy earlier. The purpose of this study was to evaluate the performances of RT-PCR Xpert® MRSA/SA technique for the detection of methicillin-resistant CoNS (MRCoNS) from deep samples in patients with PJIs. RT-PCR was tested on 72 samples. Sensitivity, specificity, positive predictive value, and negative predictive value of RT-PCR method were 0.36, 0.98, 0.90, and 0.74, respectively. Although RT-PCR may allow early microbial diagnosis of PJI due to Staphylococcus aureus (MSSA and MRSA), the low sensitivity and the high cost of this method to detect MRCoNS could limit its use in this field.

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis.

OBJECTIVE: The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)-coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6-month period, in a group of 381 HIV/HCV-coinfected patients. METHODS: Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined. RESULTS: Thirty-six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28-0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20-0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15-6.68; P=0.023) were associated with persistently normal ALT levels. CONCLUSION: The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis.

[Community-acquired urinary tract infections in 15 to 65 years old female patients in France. Susceptibility of E. coli according to history: AFORCOPI-BIO network 2003]. / Infections urinaires communautaires de la femme de 15 à 65 ans: sensibilité aux antibiotiques de E. coli en fonction des antécédents: étude AFORCOPI-BIO 2003.

OBJECTIVES: A multicenter study was implemented in order to determine the distribution and antibiotic susceptibility patterns of strains isolated from 15 to 65 year old female patients with community-acquired urinary tract infections. PATIENTS AND METHODS: From October to December 2003, 11 French private laboratories consecutively collected 420 clinical strains with medical data. Minimal inhibitory concentrations of antibiotics on E. coli were determined using the agar dilution method in a coordinating center and interpretation followed the recommendations of the Comité de l'antibiogramme de la Société française de microbiologie. RESULTS: Escherichia coli was the most prevalent pathogen (80%) followed by Proteus mirabilis (4%), Klebsiella spp (2%), other Enterobacteriaceae (4%), Enterococcus spp (3%), Staphylococcus aureus (2%), Staphylococcus saprophyticus (2%), and Streptococcus agalactiae (2%). The susceptibility of E. coli strains was 61% for amoxicillin (AMX), 93% for nalidixic acid (NAL), 97% for norfloxacin (NOR) and ciprofloxacin (CIP), 77% for cotrimoxazole (SXT), 99% for fosfomycin, gentamicin and cefotaxime. The susceptibility of E. coli was lower in case of previous treatment with beta-lactam antibiotics for AMX (84 vs 95% p=0.02) and SXT (62 vs 81% p=0.02). In the same way, previous treatment with quinolones was associated with decreased susceptibility for NAL (84 vs 95% p=0.02) and SXT (62 vs 81% p=0.02). CONCLUSIONS: In 2003, fluoroquinolones, third generation cephalosporins, aminoglycosides, and fosfomycin kept a good activity on E. coli collected from community-acquired urinary tract infections in 15 to 65 years old female patients in France.

[Genital infections in women, in community practice. Comparison of two studies, 1987 and 2002]. / Les infections génitales chez la femme en pratique de ville Enquêtes Aforcopi-BIO. Comparaison des résultats 1987 et 2002.

One thousand eight hundred and thirty-six clinical and biological cervico-vaginal flora samples from genital infections in women observed in community practice in 1987 were compared to 368 samples collected in 2001. The diagnosis of sexually transmitted infection (STI) was rarely made. Nonetheless, examining these samples made it possible either to prescribe a specific treatment for a confirmed infection (chlamydia, trichonomiasis, candidiasis, gonococci, vaginosis), or to modify a long-term treatment that was often ineffective and sometimes badly tolerated. Not all vulvar itching, associated or not with pelvic pain, is caused by mycosis. Treatment based on a syndromic approach was often ineffective, because clinical symptoms, whether isolated or associated, even when they were suggestive of an etiology, presented only a minor positive predictive value (the PPV for the association ichting + pelvic pain was only 10% for chlamydia, but 45% for candidiasis). The diagnosis of vaginosis, suggested for the past 10 years as an improvement in the diagnosis of vulvo-vaginitis, was made in only 13% of the cases. The only significant difference in our two studies was a lower number of cases of gonococci, chlamydiae, and ureaplasms in 2001, the settings having remained identical, except for a lower number of patients in 2001.

Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS.

A patient with AIDS and chronic diarrhea caused by Enterocytozoon bieneusi was successfully treated with nitazoxanide, producing a complete clinical and parasitological response, while off of antiviral therapy. This suggests that nitazoxanide may be effective in treating microsporidiosis caused by E. bieneusi, a disease for which there is no established treatment.

Mutations conferring resistance to zidovudine diminish the antiviral effect of stavudine plus didanosine.

This study evaluated the influence of zidovudine (ZDV) resistance mutations on the antiviral effect of the combination of stavudine (D4T) plus didanosine (ddI) in patients treated previously with ZDV plus zalcitabine (ddC). Twenty patients who had been treated with ZDV plus ddC for a median duration of 11 months (range, 7-42 months) were switched to D4T (40 mg twice a day [BID]) + ddI (200 mg BID) in an open pilot study lasting 6 months. The CDC classes were A (n = 10) and B (n = 10). The median baseline CD4 count was 285/mm(3) and the median baseline plasma virus RNA (Amplicor HIV Monitor RT-PCR assay) was 4.6 log copies/ml. Population-based sequence analysis detected mutations associated with resistance to reverse transcriptase (RT) inhibitors in the RT domain of virus RNA from baseline plasma samples in 13/20 (65%) patients. Twelve patients had mutations associated with zidovudine resistance (3 T215Y - M41L - L210W; 3 T215Y - M41L; 2 T215Y - L210W; 3 T215Y; 1 K70R) and 1 patient had a multi-dideoxynucleoside resistance mutation (QI5IM). Patients with a resistance mutation had a significantly lower RNA suppression after 3 and 6 months (median RNA reduction -0.5 log and -0.1 log) than the remaining patients (-1.6 log and -2 log). Fifty percent of patients with wild-type viruses had undetectable plasma RNA after 24 weeks of D4T plus ddI therapy, whereas all those with mutated viruses had HIV RNA concentration > 3 log copies/ml at week 24 (P <.05). Our finding may have implications when deciding on a second line therapy with three or four drugs that includes two new nucleoside analogues. Cross-resistance between nucleoside analogues deserves maximal attention to ensure optimal antiretroviral therapy and design algorithms for antiretroviral management based on genotypic antiretroviral resistance testing.

Highly active antiretroviral treatment initiated early in the course of symptomatic primary HIV-1 infection: results of the ANRS 053 trial.

Highly active antiretroviral treatment (HAART) was given early to 64 patients with symptomatic primary human immunodeficiency virus (HIV)-1 infection. At the time of analysis, patients had been followed up for 9-21 months. No patient had died or developed an AIDS-defining event. Survival analysis showed that by month 21 the proportion of patients with plasma HIV-1 RNA <50 copies/mL was 72% (95% confidence interval, 58%-95%) in intention-to-treat analysis. After 18 months of treatment, 50% of the patients with undetectable plasma HIV-1 RNA also had undetectable HIV-1 RNA in peripheral blood mononuclear cells (PBMC). Only 1 of 3 patients had undetectable HIV-1 RNA in lymphoid tissue, while all patients had quantifiable HIV-1 DNA both in PBMC and lymphoid tissue. The median CD4 lymphocyte increase from baseline was 230 cells/microL. These preliminary results support the use of HAART in patients with primary HIV-1 infection.

Low-dose splenic irradiation in the treatment of immune thrombocytopenia in HIV-infected patients.

PURPOSE: To determine the effect of low-dose splenic irradiation on severe Zidovudine-resistant, HIV-1-associated thrombocytopenia (HAT). METHODS AND MATERIALS: Between September 1994 and October 1996, 17 patients were included in a prospective study. The patients met the following criteria for inclusion: hemorrhagic symptoms or a platelet count below or equal to 50 x 10(9)/l and normal numbers of megakaryocytes on bone aspiration. The mean baseline platelet count was 20.3 (+/- 14.4) x 10(9)/l; four patients had a platelet count inferior to 10 x 10(9)/l. Splenic volume was defined by ultrasonography. A total dose of 9 Gy was given using an isocentric parallel pair field technique. RESULTS: One month after the end of treatment six patients had a significant rise in their platelet count. Clinically, hemorrhagic symptoms stopped for all patients that were symptomatic. Unfortunately, duration of response was short because for one patient only the platelet count remains stable with a follow-up of 6 months. All patients are alive and in recent evaluation, with four out of eight patients receiving a combination of antiretroviral therapy had a platelet count above 50 x 10(9)/l. CONCLUSION: Our results are disappointing concerning the duration of response, especially comparatively to those reported in autoimmune thrombocytopenia. Mechanisms of HAT are more complex, and megakaryocytes' infection may play an important role. Splenic irradiation should be considered as palliative treatment for the minority of patients with severe bleeding that does not respond to standard medical treatment.

Identification of Trypanosoma brucei gambiense group I by a specific kinetoplast DNA probe.

A set of 26 Trypanosoma brucei stocks from various African countries, previously characterized by multilocus enzyme electrophoresis (MLEE) for 18 polymorphic loci, have been selected to be representative of the three T. brucei classic subspecies. The kinetoplast DNA minicircle variable regions from these stocks have been amplified using the polymerase chain reaction (PCR) technique, and hybridized with the amplified variable regions of three T. brucei reference stocks, previously identified as T. brucei brucei, T. brucei gambiense, and T. brucei rhodesiense, respectively. Both T. b. brucei and T. b. rhodesiense probes hybridized only with their own stocks, but the T. b. gambiense probe specifically hybridized with a group of 12 stocks that represented most of the human stocks from West and Central Africa in our sample. These stocks, which appeared as a clearly separable cluster based on previous MLEE analysis, probably correspond to T. brucei gambiense group I. No other stock hybridized with this amplified fragment. Since the T. b. gambiense probe obtained is specific for many isolates that are pathogenic for humans in Central and West Africa, it appears to be a promising tool for epidemiologic and medical surveys.