Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

Prosthetic joint infection caused by Granulicatella adiacens: a case series and review of literature.

BACKGROUND: Bone and joint infection involving Granulicatella adiacens is rare, and mainly involved in cases of bacteremia and infectious endocarditis. Here we report three cases of prosthetic joint infection involving G. adiacens that were successfully treated with surgery and prolonged antimicrobial treatment. We also review the two cases of prosthetic joint infection involving G. adiacens that are reported in the literature. CASE PRESENTATION: Not all five cases of prosthetic joint infection caused by G. adiacens were associated with bacteremia or infectious endocarditis. Dental care before the onset of infection was observed in two cases. The median time delay between arthroplasty implantation and the onset of infection was of 4 years (ranging between 2 and 10 years). One of our cases was identified with 16srRNA gene sequencing, one case with MALDI-TOF mass spectrometry, and one case with both techniques. Two literature cases were diagnosed by 16srRNA gene sequencing. All five cases were cured after surgery including a two-stage prosthesis exchange in three cases, a one-stage prosthesis exchange in one case, and debridement, antibiotics, irrigation, and retention of the prosthesis in one case, and prolonged antimicrobial treatment. CONCLUSION: Prosthetic joint infection involving G. adiacens is probably often dismissed due to difficult culture or misdiagnosis, in particular in the cases of polymicrobial infection. Debridement, antibiotics, irrigation, and retention of the prosthesis associated with prolonged antimicrobial treatment (≥ 8 weeks) should be considered as a treatment strategy for prosthetic joint infection involving G. adiacens.

Staphylococcus lugdunensis: a neglected pathogen of infections involving fracture-fixation devices.

PURPOSE: Cases of fracture-fixation device infection involving Staphylococcus lugdunensis are not frequent. The clinical characteristics and the choice of treatment strategies of these infections are not obviously known to date. METHODS: We performed a review of fracture-fixation device infection involving S. lugdunensis managed by our centres. RESULTS: Among the 38 cases of fracture-fixation device infection involving S. lugdunensis, 53% were located in the tibia. Most of our cases (87%) were chronic infections. Purulent discharge, which occurred in 79% of cases, was the most frequent clinical symptom, followed by pain in 63%, local inflammation in 55%, and fever in 37%. Bacteremia and severe sepsis occurred in 10% and 18% of cases, respectively. Four cases (10%) were treated exclusively with antimicrobial treatment alone. Thirty-four cases (89%) were treated with a combination of surgery with antimicrobial therapy including surgical debridement, antibiotics and osteosynthesis device retention in six cases (16%), and osteosynthesis device removal in 27 cases (71%). The mean length of antibiotic treatment was 119 days. The relapse rate was high that was not related to selection of resistant strains. Polymicrobial infection had no impact on clinical outcome. A combination of surgery with antimicrobial therapy was identified as a significant prognostic factor associated with remission (p = 0.042). CONCLUSIONS: S. lugdunensis is probably involved in more infections than has been reported. Using appropriate microbiological methods laboratories should routinely identify the species of all coagulase-negative Staphylococci isolates involved in fracture-fixation device infection to better achieve the treatment strategies of fracture-fixation device infection involving S. lugdunensis.

Prosthetic joint infection caused by Pasteurella multocida: a case series and review of literature.

BACKGROUND: Pasteurella multocida is a well-recognized zoonotic agent following dog or cat bites or scratches. Nevertheless, prosthetic joint infection caused by P. multocida are rarely reported. METHOD: We report here a series of six cases of prosthetic joint infection caused by P. multocida managed at a referral centre for the treatment of bone and joint infection in southern France. We also reviewed the 26 cases reported in literature. RESULTS: The mean age of our cases was 74 years [±8.2, range 63-85]. In majority of our cases (5 cases) were associated with knee prostheses and one case with a hip prosthesis. Most of cases occurred after cat or dog scratches or licks or contact. Diagnoses of prosthetic joint infection caused by P. multocida were made by positive cultures of surgical biopsies or needle aspiration. Mean time delay between prosthetic joint implantation and infection onset was 7.6 years (±5.12 years, range 2-17). Local inflammation, which occurred in all six cases, was the most frequent clinical symptom, followed by pain in five cases, fever and swollen joints in four cases, and a fistula with purulent discharge inside the wound in two cases. The mean time of antibiotic therapy was 8 months. Surgical treatment with prosthesis removal was performed in three cases. Six of our cases were in remission without apparent relapse at 3 years after end of treatment. CONCLUSION: Prosthetic joint infections caused by P. multocida usually occur after animal scratches or bites, but can occasionally occur after a short animal lick. These infections are usually resulting from a contiguous infection and localized in the knee. An early antibiotic therapy after surgical debridement could avoid prosthetic withdrawal, notably in elderly patients. Patients with prosthetic joints should be warned that animals are potential sources of serious infection and urgent medical advice should be sought if they are bitten or scratched.

Identification of rare pathogenic bacteria in a clinical microbiology laboratory: impact of matrix-assisted laser desorption ionization-time of flight mass spectrometry.

During the past 5 years, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has become a powerful tool for routine identification in many clinical laboratories. We analyzed our 11-year experience in routine identification of clinical isolates (40 months using MALDI-TOF MS and 91 months using conventional phenotypic identification [CPI]). Among the 286,842 clonal isolates, 284,899 isolates of 459 species were identified. The remaining 1,951 isolates were misidentified and required confirmation using a second phenotypic identification for 670 isolates and using a molecular technique for 1,273 isolates of 339 species. MALDI-TOF MS annually identified 112 species, i.e., 36 species/10,000 isolates, compared to 44 species, i.e., 19 species/10,000 isolates, for CPI. Only 50 isolates required second phenotypic identifications during the MALDI-TOF MS period (i.e., 4.5 reidentifications/10,000 isolates) compared with 620 isolates during the CPI period (i.e., 35.2/10,000 isolates). We identified 128 bacterial species rarely reported as human pathogens, including 48 using phenotypic techniques (22 using CPI and 37 using MALDI-TOF MS). Another 75 rare species were identified using molecular methods. MALDI-TOF MS reduced the time required for identification by 55-fold and 169-fold and the cost by 5-fold and 96-fold compared with CPI and gene sequencing, respectively. MALDI-TOF MS was a powerful tool not only for routine bacterial identification but also for identification of rare bacterial species implicated in human infectious diseases. The ability to rapidly identify bacterial species rarely described as pathogens in specific clinical specimens will help us to study the clinical burden resulting from the emergence of these species as human pathogens, and MALDI-TOF MS may be considered an alternative to molecular methods in clinical laboratories.

Infectious endocarditis detected by PET/CT in a patient with a prosthetic knee infection: case report and review of the literature.

We report a case illustrating the potential use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) for the diagnosis of infective endocarditis (IE) in an 84-y-old woman who had a history of chronic left knee osteitis and a mitral cardiac valve bioprosthesis replacement and a pacemaker. She developed a polymicrobial knee infection 15 days after her total knee replacement. Transoesophageal echocardiography showed a new mitral regurgitation, but no vegetation or abscess. PET/CT showed hypermetabolic hyperactivity around the mitral cardiac valve prosthesis and the intracardiac pacemaker leads. We found 17 case reports and 2 case series of IE in which PET/CT showed encouraging results for the detection of IE. PET/CT may be used in patients with a suspicion of IE who do not have echocardiographic evidence of IE. It may also be useful for identifying the portal of entry of an infection and for identifying secondary foci (mycotic aneurysm).

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France.

BACKGROUND: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. METHODS: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). RESULTS: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years - range 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). CONCLUSION: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study.

BACKGROUND: We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration. METHODS: We conducted an uncontrolled, non-comparative, observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU). RESULTS: All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days. CONCLUSION: We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.

Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

BACKGROUND: Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry accurately identifies both selected bacteria and bacteria in select clinical situations. It has not been evaluated for routine use in the clinic. METHODS: We prospectively analyzed routine MALDI-TOF mass spectrometry identification in parallel with conventional phenotypic identification of bacteria regardless of phylum or source of isolation. Discrepancies were resolved by 16S ribosomal RNA and rpoB gene sequence-based molecular identification. Colonies (4 spots per isolate directly deposited on the MALDI-TOF plate) were analyzed using an Autoflex II Bruker Daltonik mass spectrometer. Peptidic spectra were compared with the Bruker BioTyper database, version 2.0, and the identification score was noted. Delays and costs of identification were measured. RESULTS: Of 1660 bacterial isolates analyzed, 95.4% were correctly identified by MALDI-TOF mass spectrometry; 84.1% were identified at the species level, and 11.3% were identified at the genus level. In most cases, absence of identification (2.8% of isolates) and erroneous identification (1.7% of isolates) were due to improper database entries. Accurate MALDI-TOF mass spectrometry identification was significantly correlated with having 10 reference spectra in the database (P=.01). The mean time required for MALDI-TOF mass spectrometry identification of 1 isolate was 6 minutes for an estimated 22%-32% cost of current methods of identification. CONCLUSIONS: MALDI-TOF mass spectrometry is a cost-effective, accurate method for routine identification of bacterial isolates in <1 h using a database comprising > or =10 reference spectra per bacterial species and a 1.9 identification score (Brucker system). It may replace Gram staining and biochemical identification in the near future.

Cervical osteomyelitis: A new identity of dreaded complication following pharyngeal cancer treatment.

BACKGROUND: Cervical osteomyelitis following the treatment of pharyngeal cancer with laryngectomy and chemoradiotherapy is poorly reported. METHODS: Six cases of cervical osteomyelitis occurring over a 1-year period are described herein. These are reviewed alongside four cases reported previously in the literature. RESULTS: Among the total 10 cases, the average age of the patients was 58.7 years. The period between laryngectomy and the diagnosis of cervical osteomyelitis was on average 3 years and 1 month and the male to female sex ratio was 9:1. Two patients had a history of cervical fistula with an esophageal prosthesis, one had a spontaneous cervical fistula, one had a pharyngeal cutaneous fistula, and one had an esophageal prosthesis without any fistula. At the time of diagnosis, seven had a history of cervical pain (70%) and nine had a neurological deficit (90%). Seven patients (70%) underwent surgery; one (10%) was contraindicated for a general anesthetic and two (20%) died before any intervention. The indication for surgery was a neurological deficit for six patients (60%) and the requirement for lavage and debridement for two patients (20%). The average length of antimicrobial treatment was 12.7 weeks. The outcome was favorable for six patients. Four patients died. CONCLUSIONS: Cervical osteomyelitis is a serious but rarely reported complication following the treatment of pharyngeal cancer with chemoradiotherapy and laryngectomy. Cervical pain was the first sign to appear, sometimes 1year before any other sign. Physicians should be aware of this dreaded complication, which is probably underdiagnosed and is related to an increased mortality rate.

The CRIOAc healthcare network in France: A nationwide Health Ministry program to improve the management of bone and joint infection.

BACKGROUND: Bone and joint infections (BJIs) have a major clinical and economic impact in industrialized countries. Its management requires a multidisciplinary approach, and a great experience for the most complicated cases to limit treatment failure, motor disability and amputation risk. To our best knowledge there is not currently national specific organization dedicated to manage BJI. Is it possible to build at a national level, a network involving orthopaedic surgeons, infectiologists and microbiologists performing locally multidisciplinary meetings to facilitate the recruitment and the management of patients with complex bone and joint infection in regional centers? HYPOTHESIS: A national healthcare network with regional labeled centers creates a dynamic that improves the recruitment, the management, the education, and the clinical research in the field of complex BJI. PATIENTS AND METHODS: We describe the history of this unique national healthcare network and how it works, specify the missions confided to the CRIOAcs, evaluate the activity of the network over the first decade, and finally discuss perspectives. RESULTS: The labelling of 24 centers in the CRIOAc network allowed for a meshing of the territory, with the possibility of management of complex BJI in each region of France. A dedicated secure national online information system was designed and used to facilitate decision-making during multidisciplinary consultation meetings. Since October 2012 to June 2017, 4553 multidisciplinary consultation meetings have been performed in the structures belonging to the network, with 34,607 cases discussed in 19,961 individual. Prosthetic joint infections represented 38% (7585/19,961) of all BJIs. Among all the cases discussed, the rate of complexity was of 61% (21,110/34,607) (related to antibiotic resistance, infection recurrence, patient co morbidities). A national scientific meeting was created and a national postgraduate diploma in the field of BJI was launched in 2014. The promotion of education, clinical research and interactivity between each academic discipline and between each labeled centers across the country has synergized the strengths and have greatly facilitated the management of patients with BJI. DISCUSSION: The setting up of the CRIOAc network in France took time, and has a cost for the French Ministry of Health. However, this network has greatly facilitated the management of BJI in France, and allowed to concentrate the management of complex BJI in centers that have significantly gained skills. There is, to our knowledge, no other exemple of such nationwide network in the field of BJI. LEVEL OF EVIDENCE: IV, case series without control group.

Genomic analysis of a Raoultella ornithinolytica strain causing prosthetic joint infection in an immunocompetent patient.

We sequenced the genome of Raoultella ornithinolytica strain Marseille-P1025 that caused a rare case of prosthetic joint infection in a 67-year-old immunocompetent male. The 6.7-Mb genome exhibited a genomic island (RoGI) that was unique among R. ornithinolytica strains. RoGI was likely acquired by lateral gene transfer from a member of the Pectobacterium genus and coded for a type IVa secretion system found in other pathogenic bacteria and that may have conferred strain Marseille-P1025 an increased virulence. Strain Marseille-P1025 was also able to infect, multiply within, and kill Acanthamoaeba castellanii amoebae.

Old antimicrobials and Gram-positive cocci through the example of infective endocarditis and bone and joint infections.

The management of some serious infections such as infective endocarditis (IE) and bone and joint infections (BJIs) caused by Gram-positive cocci (GPC) is complex and requires great responsiveness and effective antimicrobials with high bioavailability in heart valves or bone tissues. Treatment of these infections requires the use of a higher dosage that may result in increased toxicity or the use of new promising antimicrobials to control the infection. However, use of these new antimicrobials could still bring about new toxicity and resistance. Another approach may be the 'comeback' of old antimicrobials, which is evaluated in this review in the treatment of IE and BJIs caused by GPC.

Arthrocladium fulminans Arthritis and Osteomyelitis.

Arthrocladium fulminans is the only species in the Arthrocladium genus that has been involved in a previous human infection. To date, only one case of A. fulminans infection in a patient with GATA-2 immunodeficiency has been reported. We here report the second human case and the first case of septic arthritis and osteomyelitis due to A. fulminans in an immunocompetent patient, living in Mayotte, a French island in western Indian Ocean. He was successfully treated with surgical debridement and 6 months of antifungal treatment. This second observation of human invasive disease caused by A. fulminans is an additional argument for the pathogenicity of this rare species.

Misuse of antibiotics reserved for hospital settings in outpatients: a prospective clinical audit in a university hospital in Southern France.

Some antibiotics are reserved essentially for hospital settings owing to cost effectiveness and in order to fight the emerging antibiotic resistance crisis. In some cases, antibiotics reserved exclusively for use in hospitals may be prescribed in outpatients for serious infections or in the absence of a therapeutic alternative. A 30-day prospective audit of outpatient prescriptions of antibiotics reserved exclusively for use in hospitals was performed. The objective of this study was to evaluate the relevance of outpatient antibiotic prescriptions by measuring appropriateness according to guidelines. During the study period, 53 prescriptions were included, only 40% of which were appropriate. Among the 32 inappropriate prescriptions, 4 cases lacked microbial arguments, 1 case was not adequate for the infection type, 1 case involved an incorrect antibiotic dosage, 1 case involved an incorrect interval of dose administration, 3 cases had a therapeutic alternative and 22 cases were not recommended. Of the 53 prescriptions, 66% were started in hospital and 34% in outpatients. Only 25% of cases were prescribed with infectious diseases specialist (IDS) advice, 64% were based on microbiological documentation and 13% had a negative bacterial culture. Inappropriate prescriptions were usually observed in antibiotic lock therapy, skin infections, Clostridium difficile colitis, intra-abdominal infections and intravascular catheter-related infections. Outpatient prescriptions of antimicrobial drugs reserved exclusively for use in hospitals are frequently inappropriate. We recommend a real-time analysis algorithm with the involvement of an IDS for monitoring prescriptions to improve the quality of these prescriptions and possibly to prevent antibiotic resistance.

Saccharomyces cerevisiae osteomyelitis in an immunocompetent baker.

Invasive infection caused by Saccharomyces cerevisiae is rare. We report the first case of osteomyelitis caused by S. cerevisiae (baker's yeast) in a post-traumatic patient. The clinical outcome was favorable after surgical debridement, prolonged antifungal treatment and hyperbaric oxygen therapy.

Late infectious endocarditis of surgical patch closure of atrial septal defects diagnosed by 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT): a case report.

BACKGROUND: In contrast to percutaneous atrial septal occluder device, surgical patch closure of atrial defects was known to be no infective endocarditis risk. CASE PRESENTATION: We herein report the first case of late endocarditis of surgical patch closure of atrial septal defects occurred at 47-year after surgery. On September 2014, a 56-year-old immunocompetent French Caucasian man was admitted into the Emergency Department for 3-week history of headache, acute decrease of psychomotor performance and fever at 40 °C. The diagnosis has been evoked during his admission for the management of a brain abscess and confirmed using 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT). Bacterial cultures of surgical deep samples of brain abscess were positive for Streptococcus intermedius and Aggregatibacter aphrophilus as identified by the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and confirmed with 16S rRNA gene sequencing. The patient was treated by antibiotics for 8 weeks and surgical patch closure removal. CONCLUSIONS: In summary, late endocarditis on surgical patch and on percutaneous atrial septal occluder device of atrial septal defects is rare. Cardiac imaging by the 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT) could improve the diagnosis and care endocarditis on surgical patch closure of atrial septal defects while transthoracic and transesophageal echocardiography remained difficult to interpret.

Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature.

BACKGROUND: Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. CASE PRESENTATION: A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8°C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. CONCLUSIONS: In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option.

Raoultella ornithinolytica: An unusual pathogen for prosthetic joint infection.

We herein report the first case of a prosthetic joint infection caused by Raoultella ornithinolytica in an immunocompetent patient. The clinical outcome was favorable after a two-stage prosthetic exchange and a six-month course of antimicrobial therapy.