National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303–1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI.
Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa.Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy.Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II ≥40 versus <40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08-5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90-12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56-6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27-1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42-35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02-0.63, p = 0.01).In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.
The optimal length of the intravenous antibiotic treatment of periprosthetic joint infections (PJIs) generally ranges from one to six weeks and is a matter of debate. Most antibiotics active against Gram-positive cocci (GPC) exhibit both high oral bioavailability and bone diffusion. Thus, early oral therapy may be a reasonable option in GPC-related PJIs.A 2 year before and after monocentric study that aimed to compare two antibiotic strategies. Empirical intravenous postoperative antibiotic treatment was followed by 7 to 10 days of intravenous targeted therapy ('before' group) or by full orally targeted antibiotic treatment ('after' group). The primary outcome was a treatment failure during follow-up.A total of 93 patients were analysed, 43 and 50 in the before and the after groups, respectively. Both groups were comparable in terms of surgical procedures, comorbidities, microbiological documentation and infection site. Antibiotics prescribed to our patients had high oral bioavailability and bone diffusion with rifampicin/fluoroquinolone combinations being the most frequent antibiotic regimens. Both hospital stay and intravenous antibiotic treatment mean durations were shorter in the before group than in the after group [15.0 versus 11.0 days; (P < 0.01) and 13.0 versus 7.0 days; P < 0.001, respectively]. The remission rate assessed after at least a year of follow-up was comparable in the before and the after groups (hazard ratio = 0.70; 95% CI 0.30-1.58).Full oral targeted antibiotic therapy using a drug regimen with high oral bioavailability and good bone diffusion is an option for the treatment of patients with GPC-related PJIs.
The aim was to assess the incidence of sink contamination by multidrug-resistant (MDR) Pseudomonas aeruginosa and Enterobacteriaceae, risk factors for sink contamination and splashing, and their association with clinical infections in the intensive care setting.A prospective French multicentre study (1 January to 30 May 2020) including in each intensive care unit (ICU) a point-prevalence study of sink contamination, a questionnaire of risk factors for sink contamination (sink use, disinfection procedure) and splashing (visible plashes, distance and barrier between sink and bed), and a 3-month prospective infection survey.Seventy-three ICUs participated in the study. In total, 50.9% (606/1191) of the sinks were contaminated by MDR bacteria: 41.0% (110/268) of the sinks used only for handwashing, 55.3% (510/923) of those used for waste disposal, 23.0% (62/269) of sinks daily bleached, 59.1% (126/213) of those daily exposed to quaternary ammonium compounds (QACs) and 62.0% (285/460) of those untreated; 459 sinks (38.5%) showed visible splashes and 30.5% (363/1191) were close to the bed (<2 m) with no barrier around the sink. MDR-associated bloodstream infection incidence rates ≥0.70/1000 patient days were associated with ICUs meeting three or four of these conditions, i.e. a sink contamination rate ≥51%, prevalence of sinks with visible splashes ≥14%, prevalence of sinks close to the patient's bed ≥21% and no daily bleach disinfection (6/30 (20.0%) of the ICUs with none, one or two factors vs. 14/28 (50.0%) of the ICUs with three or four factors; p 0.016).Our data showed frequent and multifactorial infectious risks associated with contaminated sinks in ICUs.
The immune reconstitution inflammatory syndrome (IRIS) is a set of clinical and laboratory findings, related to the expression of opportunistic infections or of cancers. IRIS occurs in two ways: revelation (unmasked disease) or deterioration of a known infection or neoplasic disease (paradoxical reaction) [1]. It may be associated with many different opportunistic pathogens such as Mycobacterium tuberculosis, Cryptococci, JC polyomavirus, and hepatitis C and B virus [2]. This syndrome is usually characterized by an increased CD4 cell count and a rapid decrease in viral load [1]. The pathogenesis is speculative and seems to be caused by a recovery of pathogen-specific T cells responses and perturbations of innate immune responses [2]. Histoplasma capsulatum var. capsulatum is endemic in central regions of sub-Saharian Africa and in the USA (Ohiao and Mississipi River valley) [3], and is an opportunistic fungal infection in HIV-infected patients with a CD4 low cell count of less than 50 cells/μl [3]. The pathogenesis remains unclear and seems to be related to airborne contamination from the soil (bird ant bat excrements) [4]. We report a case of IRIS related to a disseminated histoplasmosis infection in an African HIV-1-infected patient living in France. A 28-year-old woman with a history of tuberculosis was diagnosed with HIV-1 after her childbirth in 2002 in Ivory Coast, and then she was lost to follow-up. In October 2011, she consulted for weight loss and fatigue. Her physical examination was unremarkable, her CD4 cell count was 3 cells/μl and viral load was 62 976 copies/ml (4.8 log). The patient started her antiretroviral therapy (ART) with tenofovir/emtricitabine, atazanavir and ritonavir, but she stopped it 1 month later because of a digestive intolerance and came back to the hospital. Abdominal computed tomography (CT) scan found mesenteric and retroperitoneal adenopathies without necrosis (the largest one measured 23 × 12 mm). The patient refused further investigations and a new ART regimen was started in November with abacavir/lamivudine, darunavir and ritonavir. Two months later, she presented with fever, night sweats and multiple cervical adenopathies. CD4 cell count was 10 cells/μl, viral load was 235 copies/ml (3.37 log) and C-reactive protein was less than 5. Sputum and blood testing did not find any fungal, bacterial or viral infection. The second tomography revealed multiple mesenteric, cervical and retroperitoneal adenopathies with central necrosis, with an increase of the latero aortic one, which measured 36 mm. The biopsy of a cervical adenopathy revealed a necrotizing lymphadenitis with typical yeast bodies of Histoplasma sp. (Fig. 1). Liposomal Amphotericin B treatment (3 mg/kg) has been infused for 3 weeks and switched to itraconazole (200 mg × 2) for several weeks. The patient slowly felt well. Histoplasmosis was considered cured as the patient continued ART with a favourable immunovirological status.Fig. 1: Numerous clusters of Histoplasma capsulatum cells in macrophages (arrow: periodic acid-Schiff stain).We described a disseminated histoplasmosis after reintroduction of ART, probably related to an unmasked IRIS because of a more than 50% increase in CD4 cell count and a more than 1 log10 decrease in viral load. This is rarely described in the literature [5], and histoplasmosis is rare outside disease-endemic areas [6], although our patient was born in the Ivory Coast but did not return to Africa since 2000. Because of the lack of compliance of this patient, the diagnosis of IRIS could be discussed. Marc De Lavaissière et al.[5] reported a case of IRIS related to H. capsulatum in an HIV-infected patient born in French Guyana, who did not travel to South America or Africa. This case was associated with a haemophagocytic syndrome, which was not the case of our patient. Breton et al.[7] have already reported four cases of patients infected with HIV-1 from Surinam, Ivory Coast, Congo and French Guyana who were showing different clinical signs due to disseminated histoplasmosis (Histoplasma variety capsulatum and duboisii), after initiation of ART. They found granulomas with caseation in the three cases, which are typically associated with immunocompetent patients and attributed to IRIS [7]. In our patient, the histological analysis revealed a necrotizing lymphadenitis, which had been described in a immunocompetent patient with a cervical localization as an unusual presentation in chronic-disseminated histoplasmosis [8]. Finally, histoplasmosis is a differential diagnosis of tuberculosis [9] and even lymphoma, in an immunocompromized patient coming from endemic areas, and presenting with fever, asthenia, weight loss, sweats and lymph nodes such as in our patient [10]. In conclusion, histoplasmosis is an opportunistic infection that can be revealed by an unmasked IRIS in HIV-infected patients on ART and should be suspected in case of fever, alteration of general conditions and lymphadenitis, even outside disease-endemic areas. Acknowledgements Conflicts of interest There are no conflicts of interest.
