A Case of Confusion in an Obese Patient Treated With Daptomycin: Neurotoxicity.

Daptomycin (DAP) is a cyclic lipopeptide antibiotic with bactericidal activity against gram-positive bacteria. The most common adverse reaction is myotoxicity characterized by rhabdomyolysis. Other reported adverse reactions include gastrointestinal symptoms, skin lesions, bleeding, and pulmonary involvement. Neurotoxicity is rare and its mechanism remains partially elucidated. We report a case of confusion consistent with DAP-induced neurotoxicity. A 73-year-old obese man was treated with DAP 9 mg/kg for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia associated with foot osteitis and cervical posterior inter-apophyseal arthritis. On the fifth day of treatment, he developed spatial disorientation, and serum DAP concentrations were very high. DAP-induced neurotoxicity was suggested. His neurological status returned to normal after treatment was stopped. This observation describes a relationship between confusion and DAP that is favored by obesity. Clinicians should be alert for neurologic disorders associated with DAP. It is prudent to reduce doses in obese patients.

ddPCR increases detection of SARS-CoV-2 RNA in patients with low viral loads.

RT-qPCR detection of SARS-CoV-2 RNA still represents the method of reference to diagnose and monitor COVID-19. From the onset of the pandemic, however, doubts have been expressed concerning the sensitivity of this molecular diagnosis method. Droplet digital PCR (ddPCR) is a third-generation PCR technique that is particularly adapted to detecting low-abundance targets. We developed two-color ddPCR assays for the detection of four different regions of SARS-CoV-2 RNA, including non-structural (IP4-RdRP, helicase) and structural (E, N) protein-encoding sequences. We observed that N or E subgenomic RNAs are generally more abundant than IP4 and helicase RNA sequences in cells infected in vitro, suggesting that detection of the N gene, coding for the most abundant subgenomic RNA of SARS-CoV-2, increases the sensitivity of detection during the highly replicative phase of infection. We investigated 208 nasopharyngeal swabs sampled in March-April 2020 in different hospitals of Greater Paris. We found that 8.6% of informative samples (n = 16/185, P < 0.0001) initially scored as "non-positive" (undetermined or negative) by RT-qPCR were positive for SARS-CoV-2 RNA by ddPCR. Our work confirms that the use of ddPCR modestly, but significantly, increases the proportion of upper airway samples testing positive in the framework of first-line diagnosis of a French population.

Evaluation of a commercial immunochromatographic assay for rapid routine identification of PBP2a-positive Staphylococcus aureus and coagulase-negative staphylococci.

We evaluated the performance of an immunochromatographic assay (PBP2a Culture Colony Test - Alere™), detecting protein-binding penicillin 2a on staphylococci primary isolates in only 6minutes. The assay is highly sensitive for the direct detection of MRSA on various culture media whereas it requires cefoxitin induction for methicillin-resistant coagulase-negative staphylococci.

Methicillin-resistant Staphylococcus capitis with reduced vancomycin susceptibility causes late-onset sepsis in intensive care neonates.

BACKGROUND: Coagulase-negative staphylococci, mainly Staphylococcus epidermidis, are the most frequent cause of late-onset sepsis (LOS) in the neonatal intensive care unit (NICU) setting. However, recent reports indicate that methicillin-resistant, vancomycin-heteroresistant Staphylococcus capitis could emerge as a significant pathogen in the NICU. We investigated the prevalence, clonality and vancomycin susceptibility of S. capitis isolated from the blood of NICU infants and compared these data to adult patients. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a retrospective laboratory-based survey of positive blood cultures in NICU infants ≥ 3 days of age (n = 527) and in adult ICU patients ≥ 18 years of age (n = 1473) who were hospitalized from 2004 to 2009 in two hospital centers in Lyon, France. S. capitis was the most frequent pathogen in NICU infants, ahead of S. epidermidis (39.1% vs. 23.5% of positive blood cultures, respectively). Conversely, S. capitis was rarely found in adult ICU patients (1.0%) compared to S. epidermidis (15.3%). S. capitis bloodstream isolates were more frequently resistant to methicillin when collected from NICU infants than from adult patients (95.6% vs. 53.3%, respectively). Furthermore, we collected and characterized 53 S. capitis bloodstream isolates from NICU infants and adult patients from six distant cities. All methicillin-resistant S. capitis isolates from NICU infants were clonally related as determined by pulsed-field gel electrophoresis. These isolates harbored a type V-related staphylococcal chromosomal cassette mec element, and constantly showed either vancomycin resistance (37.5%) or heteroresistance (62.5%). Conversely, the isolates that were collected outside of the NICU were genetically diverse and displayed much lower rates of vancomycin resistance and heteroresistance (7.7% and 23.1%, respectively). CONCLUSIONS/SIGNIFICANCE: A clonal population of methicillin-resistant S. capitis strains has spread into several French NICUs. These isolates exhibit reduced susceptibility to vancomycin, which is the most widely used antimicrobial agent in the NICU setting.

Toxin profiling of Staphylococcus aureus strains involved in varicella superinfection.

The most common complications of varicella are bacterial skin and soft tissue infections, generally due to Staphylococcus aureus and group A beta-hemolytic streptococci. The aim of this study was to characterize the toxin and antibiotic resistance profiles of S. aureus isolates involved in varicella complications. Between 2002 and 2007, the French Reference Centre for Staphylococci collected 58 S. aureus isolates involved in varicella superinfection. All the isolates were characterized by screening for 12 toxin genes, agr typing, and mecA gene detection; some isolates were also studied by spa typing, multilocus sequence typing (MLST), and resistance profiling. A major toxin gene was detected in 53% (31/58) of the isolates (genes for exfoliative toxins A and B, 17.2%; Panton-Valentine leukocidin gene, 8.6%; toxic shock syndrome toxin 1 gene, 27.6%). Most clinical manifestations were directly compatible with the classical activity of these toxins. Nineteen isolates (33%) were resistant to methicillin, and 12 of these isolates belonged to an emerging agr-2, ST5 clone that harbors the toxic shock syndrome toxin 1 gene. These data should be considered in the management and treatment of patients with varicella complicated by S. aureus superinfection. Antibiotics that decrease toxin production, such as clindamycin, may provide benefit, and their efficacy against bacterial superinfections in children with varicella should be studied.

Concurrent dengue and malaria in Cayenne Hospital, French Guiana.

Dengue-malaria co-infection reports are scarce. Of 1,723 consecutive febrile patients in Cayenne Hospital, 238 had dengue (174 early dengue fever cases) and 393 had malaria (371 acute malaria); 17 had both. Diagnosis of 1 of these 2 infections should not rule out testing for the other infection.