Impact of Enterococcus faecalis Endocarditis Treatment on Risk of Relapse.

BACKGROUND: Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. MATERIALS: This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. RESULTS: Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death.The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis). CONCLUSIONS: Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.

A clinical decision rule to rule out bloodstream infection in the emergency department: retrospective multicentric observational cohort study.

BACKGROUND: We aimed to identify patients at low risk of bloodstream infection (BSI) in the ED. METHODS: We derived and validated a prediction model to rule out BSI in the ED without the need for laboratory testing by determining variables associated with a positive blood culture (BC) and assigned points according to regression coefficients. This retrospective study included adult patients suspected of having BSI (defined by at least one BC collection) from two European ED between 1 January 2017 and 31 December 2019. The primary end point was the BSI rate in the validation cohort for patients with a negative Bacteremia Rule Out Criteria (BAROC) score. The effect of adding laboratory variables to the model was evaluated as a second step in a two-step diagnostic strategy. RESULTS: We analysed 2580 patients with a mean age of 64 years±21, of whom 46.1% were women. The derived BAROC score comprises 12 categorical clinical variables. In the validation cohort, it safely ruled out BSI without BCs in 9% (58/648) of patients with a sensitivity of 100% (95% CI 95% to 100%), a specificity of 10% (95% CI 8% to 13%) and a negative predictive value of 100% (95% CI 94% to 100%). Adding laboratory variables (creatinine ≥177 µmol/L (2.0 mg/dL), platelet count ≤150 000/mm3 and neutrophil count ≥12 000/mm3) to the model, ruled out BSI in 10.2% (58/570) of remaining patients who had been positive on the BAROC score. The BAROC score with laboratory results had a sensitivity of 100% (95% CI 94% to 100%), specificity of 11% (95% CI 9% to 14%) and negative predictive value of 100% (95% CI 94 to 100%). In the validation cohort, there was no evidence of a difference in discrimination between the area under the receiver operating characteristic for BAROC score with versus without laboratory testing (p=0.6). CONCLUSION: The BAROC score safely identified patients at low risk of BSI and may reduce BC collection in the ED without the need for laboratory testing.

Cerebral epidural empyema due to Bartonella henselae: a case report.

BACKGROUND: Cat scratch disease frequently involves a benign, self-limited disease. Neurological forms associated with Bartonella henselae are uncommon, consisting mostly in neuroretinitis, encephalitis and meningitis. Cerebral epidural empyema has never described. CASE PRESENTATION: An adult patient was hospitalized for isolated headaches. Magnetic Resonance Imaging (MRI) identified typical features of cerebral epidural empyema. The diagnosis of B. henselae was performed incidentally by 16S rDNA gene sequencing on the abscess fluid, and confirmed by specific qPCR. We report here the first case, to our knowledge, of cerebral epidural empyema associated with B. henselae. Further follow-up visits allowed identifying frequent cat scratches on the scalp as the presumptive source of infection. CONCLUSIONS: This case report alerts about such atypical clinical presentation, which requires an extensive clinical investigation. It also emphasizes on the usefulness of additional molecular diagnosis techniques in such CNS infection cases.

Performance of penicillinase detection tests in Staphylococcus epidermidis: comparison of different phenotypic methods.

BACKGROUND: Staphylococcus epidermidis is the leading coagulase negative staphylococci (CoNS) species associated with healthcare associated infections. In order to de-escalate antimicrobial therapy, isolates of S. epidermidis lacking the blaZ gene should be eligible for targeted antimicrobial therapy. However, testing the susceptibility of coagulase negative staphylococci (CoNS) to penicillin G is no longer recommended by EUCAST, given the low performances for penicillinase detection in CoNS. The objective of this work was to determine a phenotypic method with high performance for detecting penicillinase production in S. epidermidis. RESULTS: Four techniques for the detection of penicillinase production (disk diffusion, zone edge test, nitrocefin test, Minimal Inhibitory Concentration (MIC) by automated system Vitek2®) were evaluated on 182 S. epidermidis isolates, using identification of blaZ gene by PCR as the reference method. The performance of the methods for penicillinase detection was compared by the sensitivity, the specificity, the negative predictive value and the positive predictive value, and with Cohen's kappa statistical test. Among the 182 S. epidermidis included in this study, 55 carried the blaZ gene. The nitrocefin test, characterized by a poor sensitivity (91%), was therefore excluded from S. epidermidis penicillinase detection. The algorithm proposed here for the penicillinase detection in S. epidermidis involved two common antimicrobial susceptibility techniques: disk diffusion method and MIC by Vitek2® system. Disk diffusion method, interpreted with a 26 mm breakpoint for penicillin G, was associated with a high sensitivity (98%) and specificity (100%). This method was completed with zone edge test for S. epidermidis with penicillin G diameter from 26 to 35 mm (sensitivity of 98%). The Vitek2® system is associated with a low sensitivity (93%) and a high specificity (99%) This low sensitivity is associated with false negative results, in isolates with 0.12 mg/L Penicillin G MIC values and blaZ positive. Thus for penicillin G MIC of 0.06 mg/L or 0.12 mg/L, a second step with disc diffusion method is suggested. CONCLUSIONS: According to our results, the strategy proposed here allows the interpretation of penicillin G susceptibility in S. epidermidis isolates, with an efficient detection of penicillin G resistance.

Performance of the extended use of the FilmArray® BCID panel kit for bronchoalveolar lavage analysis.

Ventilator-associated pneumonia (VAP) are responsible for an increase in morbidity, mortality, and prolonged hospital stay. A multiplex PCR kit such as the FilmArray® BCID panel could allow early adaptation of antimicrobial therapy, which is crucial for clinical outcomes. The purpose of this study was to test the performances of FilmArray® BCID panel for the detection of bacteria producing VAP. We tested the FilmArray® BCID panel on 50 bronchoalveolar lavages (BALs), from patients hospitalized in two intensive care units at the Angers university hospital, compared to the conventional culture-based method. The sensitivity and the specificity of the FilmArray® BCID panel were 67.2% and 98.9% respectively. They were 88.6% and 98.3% respectively when considering BALs with a positive culture > 104 CFU/mL, and 94.7% and 99.6% respectively if considering BALs with a positive direct examination. This study underlines the good performance of the FilmArray® BCID panel for BAL fluid analysis. In case of positive direct examination, this test allows reliable results that can be obtained at an early stage, facilitating the early adaptation of antimicrobial therapy.

BIOFIRE® Blood Culture IDentification 2 (BCID2) panel for early adaptation of antimicrobial therapy in adult patients with bloodstream infections: a real-life experience.

Our objective was to assess the effectiveness of a multiplex PCR panel for blood culture identification (BCID2) on the implementation of appropriate antimicrobial therapy. We conducted a monocentric pre/post study comparing the time to result from direct microscopic examination (DE) to bacterial identification (BI) in positive blood cultures between 2 different periods: P1 without BCID2 and P2 with BCID2. Appropriate treatments prescribed before DE and after DE / BCID2 and after BI / BCID2 were compared using direct proportion comparison and survival analysis. For mono-microbial bloodstream infections, the proportion of appropriate antimicrobial treatment after DE was 50% in P1 vs. 87.5% after BCID2 in P2 (P < 0.001) for Gram-negative bacteria and 33.0% in P1 vs. 64.4% in P2 (P < 0.01) for Gram-positive bacteria. A significant difference (P = 0.04) was recorded with survival curves for Gram positive bacteria. BCID2 seems effective in reducing the time for prescribing appropriate antimicrobials.

Multicenter Evaluation of the FilmArray Blood Culture Identification 2 Panel for Pathogen Detection in Bloodstream Infections.

The FilmArray Blood Culture Identification 2 panel (BCID2; bioMérieux) is a fully automated PCR-based assay for identifying bacteria, fungi, and bacterial resistance markers in positive blood cultures (BC) in about 1 h. In this multicenter study, we evaluated the performance of the BCID2 panel for pathogen detection in positive BC. Conventional culture and BCID2 were performed in parallel at four tertiary-care hospitals. We included 152 positive BC-130 monomicrobial and 22 polymicrobial cultures-in this analysis. The BCID2 assay correctly identified 90% (88/98) of Gram-negative and 89% (70/79) of Gram-positive bacteria. Five bacterial isolates targeted by the BCID2 panel and recovered from five positive BC, including three polymicrobial cultures, were missed by the BCID2 assay. Fifteen isolates were off-panel organisms, accounting for 8% (15/182) of the isolates obtained from BC. The mean positive percent agreement between the BCID2 assay and standard culture was 97% (95% confidence interval, 95 to 99%), with agreement ranging from 67% for Candida albicans to 100% for 17 targets included in the BCID2 panel. BCID2 also identified the blaCTX-M gene in seven BC, including one for which no extended-spectrum ß-lactamase (ESBL)-producing isolate was obtained in culture. However, it failed to detect ESBL-encoding genes in three BC. Two of the 18 mecA/C genes detected by the BCID2 were not confirmed. No carbapenemase, mecA/C, or MREJ targets were detected. The median turnaround time was significantly shorter for BCID2 than for culture. The BCID2 panel may facilitate faster pathogen identification in bloodstream infections. IMPORTANCE Rapid molecular diagnosis combining the identification of pathogens and the detection of antibiotic resistance genes from positive blood cultures (BC) can improve the outcome for patients with bloodstream infections. The FilmArray BCID2 panel, an updated version of the original BCID, can detect 11 Gram-positive bacteria, 15 Gram-negative bacteria, 7 fungal pathogens, and 10 antimicrobial resistance genes directly from a positive BC. Here, we evaluated the real-life microbiological performance of the BCID2 assay in comparison to the results of standard methods used in routine practice at four tertiary care hospitals.

Clinical, Bacteriological, and Genetic Characterization of Bone and Joint Infections Involving Linezolid-Resistant Staphylococcus epidermidis: a Retrospective Multicenter Study in French Reference Centers.

The choice of the best probabilistic postoperative antibiotics in bone and joint infections (BJIs) is still challenging. Since the implementation of protocolized postoperative linezolid in six French referral centers, linezolid-resistant multidrug-resistant Staphylococcus epidermidis (LR-MDRSE) strains were isolated in patients with BJI. We aimed here to describe clinical, microbiological, and molecular patterns associated with these strains. All patients with at least one intraoperative specimen positive for LR-MDRSE between 2015 and 2020 were included in this retrospective multicenter study. Clinical presentation, management, and outcome were described. LR-MDRSE strains were investigated by MIC determination for linezolid and other anti-MRSA antibiotics, characterization of genetic determinants of resistance, and phylogenetic analysis. Forty-six patients (colonization n = 10, infection n = 36) were included in five centers, 45 had prior exposure to linezolid, 33 had foreign devices. Clinical success was achieved for 26/36 patients. Incidence of LR-MDRSE increased over the study period. One hundred percent of the strains were resistant to oxazolidinones, gentamicin, clindamycin, ofloxacin, rifampicin, ceftaroline, and ceftobiprole, and susceptible to cyclins, daptomycin, and dalbavancin. Susceptibility to delafloxacin was bimodal. Molecular analysis was performed for 44 strains, and the main mutation conferring linezolid resistance was the 23S rRNA G2576T mutation. All strains belonged to the sequence type ST2 or its clonal complex, and phylogenetic analysis showed emergence of five populations corresponding geographically to the centers. We showed the emergence of new clonal populations of highly linezolid-resistant S. epidermidis in BJIs. Identifying patients at risk for LR-MDRSE acquisition and proposing alternatives to systematic postoperative linezolid use are essential. IMPORTANCE The manuscript describes the emergence of clonal linezolid-resistant strains of Staphylococcus epidermidis (LR-MDRSE) isolated from patients presenting with bone and joint infections. Incidence of LR-MDRSE increased over the study period. All strains were highly resistant to oxazolidinones, gentamicin, clindamycin, ofloxacin, rifampicin, ceftaroline, and ceftobiprole, but were susceptible to cyclins, daptomycin, and dalbavancin. Susceptibility to delafloxacin was bimodal. The main mutation conferring linezolid resistance was the 23S rRNA G2576T mutation. All strains belonged to the sequence type ST2 or its clonal complex, and phylogenetic analysis showed emergence of five populations corresponding geographically to the centers. LR-MDRSE bone and joint infections seem to be accompanied by an overall poor prognosis related to comorbidities and therapeutic issues. Identifying patients at risk for LR-MDRSE acquisition and proposing alternatives to systematic postoperative linezolid use become essential, with a preference for parenteral drugs such as lipopeptids or lipoglycopeptids.

Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) can be difficult to diagnose, especially in severe forms. The Xpert MTB/RIF Ultra test introduced an additional category called trace to reference very small amounts of Mycobacterium tuberculosis complex (MTBC) DNA. The objective of our multicenter study was to evaluate whether the trace result on an extrapulmonary (EP) sample is a sufficient argument to consider diagnosing tuberculosis and starting treatment, even in severe cases. METHODS: A retrospective, multicenter cohort study was conducted from 2018 to 2022. Patients strongly suspected of EPTB with a trace result on an EP specimen were included. Hospital records were reviewed for clinical, treatment, and paraclinical data. RESULTS: A total of 52 patients were included, with a severe form in 22/52 (42.3%) cases. Culture was positive for MTBC in 33/46 (71.7%) cases. Histological analysis showed granulomas in 36/45 (80.0%) cases. An Ultra trace result with a presumptive diagnosis of TB led to the decision to treat 41/52 (78.8%) patients. All patients were started on first-line anti-TB therapy (median duration of 6.1 months), with a favorable outcome in 31/35 (88.6%) patients. The presence of a small amount of MTBC genome in EPTB is a sufficient argument to treat patients across a large region of France.

Identification of Streptomyces spp. in a Clinical Sample: Always Contamination? Results of a French Retrospective Study.

Background: Streptomyces are environmental gram-positive bacilli that can cause ubiquitous mycetoma and, more rarely, invasive infections. We describe the clinical relevance of Streptomyces spp. identified in human samples and characteristics of patients with invasive Streptomyces infections. Methods: We conducted a retrospective (2006-2017) study of Streptomyces isolates identified in clinical samples in French microbiology laboratories. Streptomyces genus was confirmed by a specific 16S rRNA polymerase chain reaction, and antibiotic susceptibility testing was performed by disk diffusion and trimethoprim-sulfamethoxazole minimum inhibitory concentration (E-test) if resistance was suspected. Patient characteristics, treatments, and outcomes were collected. Invasive infection was defined as a positive culture from a sterile site with signs of infection but without cutaneous inoculation. Results: Of 137 Streptomyces isolates, all were susceptible to amikacin (113/113) and linezolid (112/112), and 92.9% to imipenem (105/113). Using disk diffusion, 50.9% (57/112) of isolates were susceptible to trimethoprim-sulfamethoxazole, but most of the apparently resistant isolates (25/36, 69.4%) tested by E-test were ultimately classified as susceptible. Clinical data were obtained for 63/137 (45.9%) isolates: 30 (47.6%) invasive infections, 8 (12.7%) primary cutaneous infections, 22 (34.9%) contaminations, 3 (4.7%) respiratory colonization. Patients with invasive infection were more frequently receiving corticosteroids than patients without invasive infection (11/30, 36.7%, vs 2/25, 8.0%; P = .03), and at 6-month follow-up, 14 of them were cured, 3 had relapsed, 4 were dead, and 9 were lost to follow-up. Conclusions: Half of the clinical samples that grew Streptomyces were from patients with invasive infection. In that case, antimicrobial therapy should include 1 or 2 antibiotics among linezolid, amikacin, or imipenem.

Impact of ceftriaxone and temocillin on fecal abundance of extended-spectrum ß-lactamase producing Escherichia coli in a mouse model.

BACKGROUND: Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice. METHODS: Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E. coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E. coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E. coli isolates with different temocillin minimum inhibitory concentrations. RESULTS: Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E. coli. In contrast, temocillin had no effect or transiently decreased the number of 3GCR E. coli. Results obtained with the two strains were similar. CONCLUSION: Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E. coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.

Assessment of a Multiplex Serological Test for the Diagnosis of Prosthetic Joint Infection: a Prospective Multicentre Study.

Introduction: The diagnosis of prosthetic joint infections (PJIs) can be difficult in the chronic stage and is based on clinical and paraclinical evidence. A minimally invasive serological test against the main pathogens encountered during PJI would distinguish PJI from mechanical loosening. Methods: We performed a prospective, multicentre, cross-sectional study to assess the contribution of serology in the diagnosis of PJI. Over a 2-year period, all patients undergoing prosthesis revision were included in the study. A C-reactive protein assay and a serological test specifically designed against 5 bacterial species (Staphylococcus aureus, S. epidermidis, S. lugdunensis, Streptococcus agalactiae, Cutibacterium acnes) were performed preoperatively. Five samples per patient were taken intraoperatively during surgery. The diagnosis of PJI was based on clinical and bacteriological criteria according to guidelines. Results: Between November 2015 and November 2017, 115 patients were included, 49 for a chronic PJI and 66 for a mechanical problem. Among patients with PJI, a sinus tract was observed in 32.6% and a C-reactive protein level ≥10 mg/L in 74.5%. The PJI was monomicrobial in 43 cases (targeted staphylococci, 24; S. agalactiae, 1; C. acnes, 2; others, 16), and polymicrobial in 6 cases (12.2%). Sensitivity, specificity, positive predictive value and negative predictive value were 75.0%, 82.1%, 58.3% and 90.8%, respectively, for targeted staphylococci. Specificity/negative predictive value was 97.3%/100% for S. agalactiae and 83.8% /96.9% for C. acnes. Conclusions: The serological tests are insufficient to affirm the diagnosis of PJI for the targeted bacteria. Nevertheless, the excellent NPV may help clinicians to exclude PJI.

Pasteurella bacteraemia: Impact of comorbidities on outcome, based on a case series and literature review.

OBJECTIVES: Pasteurella bacteraemia is rare, but has been associated with a high mortality rate. The aim of this study was to estimate the impact of comorbidities on patients with Pasteurella bacteraemia. METHODS: All cases of Pasteurella bacteraemia in adults treated in our centre between January 2008 and December 2017 were included retrospectively and compared with cases identified in a systematic review of the literature via MEDLINE covering the years 1951-2017. The epidemiological, bacteriological, and clinical data were collected, as well as the instances of death after 30 days. RESULTS: Twenty cases of Pasteurella bacteraemia identified in our centre and 99 cases from the literature review were included. A major comorbidity was found in 80/119 (67.2%) patients. The death rate at 30 days was 31.1%. The most common comorbidities were cirrhosis, immunosuppressive therapy, and malignant diseases. Age was not associated with mortality. On multivariate analysis, the only factor associated with mortality was a major comorbidity (odds ratio 2.78, 95% confidence interval 1.01-7.70; p = 0.04). CONCLUSIONS: This study confirms the high mortality rate and highlights the importance of the host background, independent of age, in Pasteurella bacteraemia. Clinicians should be aware of the comorbidities in cases of Pasteurella infection, due to the poor prognosis of bacteraemia.

A case of Ureaplasma parvum meningitis in an adult after transphenoidal ablation of craniopharyngioma.

We report the case of a Ureaplasma parvum meningitis in an immunocompetent patient, 17 days after surgical ablation of a craniopharyngioma. Presence of U. parvum in the cerebrospinal fluid was assessed by 16S rDNA sequencing and U. parvum specific PCR. This article details a surprising complication in an adult of a transphenoidal surgery for ablation of a craniopharyngioma. This is the first case, to our knowledge, of U. parvum meningitis in an adult patient.

Colistin-glycopeptide combinations against multidrug-resistant Acinetobacter baumannii in a mouse model of pneumonia.

Aim: To assess the effect of colistin-glycopeptide combination against a multidrug-resistant strain of Acinetobacter baumannii. Materials & methods: We used in vitro procedures (Etest method, checkerboard test and kill-time assays) and a mouse model of a carbapenem-resistant A. baumannii pneumonia. Results: The colistin-teicoplanin combination allowed a 74% increase of the survival in the mouse model within the 4 days following bacterial inoculation as compared with saline or colistin alone (p = 0.06). Concurrently, the colistin-vancomycin combination presented a similar efficacy as compared with saline or colistin alone in the mouse model. Conclusion: According to those preliminary results, using the colistin-teicoplanin combination in therapeutic deadlocks encountered in certain multiresistant A. baumannii pneumonia could be envisaged if the results are confirmed.

A rare case of Prosthetic Joint Infection associated with Coxiella burnetii.

We report here the case of a Prosthetic Joint Infection (PJI) associated with Coxiella burnetii in a 62-year-old man with a revised total hip arthroplasty. The diagnosis was performed first by 16S rDNA sequencing on hip fluid aspirate, and confirmed by specific qPCR. Q fever has been reported in few cases of Prosthetic Joint Infections, often associated with chronic evolution and iterative surgeries. This case report alerts about such an unexpected diagnosis in a patient with no known risk factors.

Staphylococcus saprophyticus: Which beta-lactam?

BACKGROUND: Staphylococcus saprophyticus is resistant to the drugs most often used for the empirical treatment of urinary tract infections (UTI). The adequacy of antimicrobial treatments prescribed for UTI due to S. saprophyticus is not usually questioned. This study described the epidemiology of such infections and assessed the susceptibility of S. saprophyticus to ceftriaxone and amoxicillin-clavulanic acid. METHODS: Methicillin-susceptible S. saprophyticus (MSSS) isolated from clinical samples between November 2014 and July 2016 were included. Clinical data were recorded. The minimum inhibitory concentrations (MICs) of amoxicillin-clavulanic acid and ceftriaxone were measured for these MSSS strains and for 17 randomly selected methicillin-susceptible Staphylococcus aureus (MSSA) strains. RESULTS: Of the S. saprophyticus isolates from urine, 59.5% were associated with a diagnosis of cystitis and 33.3% with pyelonephritis. Sixty percent of S. saprophyticus cystitis cases and 25% of pyelonephritis cases were given an inappropriate antibiotic regimen. The MICs of ceftriaxone ranged from 4 to >32µg/ml for MSSS, and from 1.5 to 4µg/ml for MSSA. CONCLUSIONS: Many UTIs were treated with an empirical antibiotic therapy that was ineffective for S. saprophyticus, revealing that S. saprophyticus is an aetiology that is insufficiently considered in UTI. High MICs for ceftriaxone in MSSS were observed, which raises questions about the use of this antibiotic in UTIs due to S. saprophyticus.

Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency.

Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent hyperbilirubinemia. Several causes of corpuscular hemolysis have been described, among which red blood cell enzyme defects are of particular concern. We report a rare case of red blood cell enzyme defect in a male infant, who presented during his first months of life with recurrent and isolated neonatal hemolysis. All main causes were ruled out. At 6.5 months of age, the patient presented with gastroenteritis requiring hospitalization; fortuitously, urine organic acid chromatography revealed a large peak of 5-oxoproline. Before the association between HA and 5-oxoprolinuria was noted, glutathione synthetase deficiency was suspected and confirmed by a low glutathione synthetase concentration and a collapse of glutathione synthetase activity in erythrocytes. Moreover, molecular diagnosis revealed 2 mutations in the glutathione synthetase gene: a previously reported missense mutation (c.[656A>G]; p.[Asp219Gly]) and a mutation not yet described in the binding site of the enzyme (c.[902T>C]; p.[Leu301Pro]). However, 15 days later, a control sample revealed no signs of 5-oxoprolinuria and the clinical history discovered administration of acetaminophen in the 48 hours before hospitalization. Thus, in this patient, acetaminophen exposure allowed the diagnosis of a mild form of glutathione synthetase deficiency, characterized by isolated HA. Early diagnosis is important because treatment with bicarbonate, vitamins C and E, and elimination of trigger factors are recommended to improve long-term outcomes. Glutathione synthetase deficiency should be screened for in cases of unexplained newborn HA.