Cefepime use: A need for antimicrobial stewardship.

OBJECTIVES: Unlike other 3GCs, Cefepime is a cephalosporin that has, in animal model studies, shown a low risk of selecting resistant mutants. It also enables carbapenems to be saved in treatment of Pseudomonasaeruginosa and the CESP group (Citrobacter, Enterobacter, Serratia and Providencia, as well as the genus Klebsiellaaerogenes, Morganella and Hafnia), consequently producing cephalosporinase. We aimed to determine whether its prescription in a French teaching hospital met criteria for proper use. PATIENTS AND METHODS: We conducted a retrospective study of proper cefepime use between March 1st, 2018 and February 28th, 2019, to assess indication, antimicrobial stewardship, dosing schedule, microbiological documentation, reevaluation, and treatment duration. Prescriptions were then compared to local guidelines established from international literature. RESULTS: Out of 142 cefepime prescriptions, 97.2% were prescribed as validated according to indication. The duration of the documented treatments matched the guidelines for 56.5% of patients, dosage was adapted to the indication for 77.4% and to kidney function for 97.2%. Bacteriological documentation was performed in all cases and an antibiogram was generated in 99.2% of cases. The treatment was reassessed between 48 and 72h and between the 7th and 10th day for 44.2% and 60.9% of the prescriptions respectively. The antimicrobial stewardship team managed half of the prescriptions. Only 13.4% of prescriptions met all criteria for proper use. CONCLUSION: Notwithstanding a highly sizable majority of validated indications, a very small proportion of cefepime prescriptions met all the criteria for proper use. In the context of increased cefepime consumption, which is favored by its increased place in the latest recommendations published in 2019, proper use of cefepime prescriptions needs to be more effectively promoted.

Case Report: Leishmania and HIV Co-Diagnosis: How to Understand Medical History?

We report a case of a severe visceral leishmaniasis revealing an HIV-1 infection presenting as an acute primary infection. A young French man living in Paris with history of unprotected sex with a recent male partner and recent travel in Greece was admitted in our Infectious Diseases Department, presenting with acute febrile psychotic disorder, and positive HIV-1 serology with high viral load, very low CD4+ T-cells count and a western blot pattern suggesting an acute infection. The psychotic disorder was finally related to hemophagocytic lymphohistiocytosis diagnosed on bone marrow aspiration, supposedly secondary to HIV acute primary infection. The progressive worsening of pancytopenia despite antiretroviral treatment and the persistence of fever, chills and sweat led to the diagnosis of visceral leishmaniasis through bone marrow biopsy and leishmanial serology. He was treated with intravenous liposomal amphotericin B with quick improvement. We discuss the way HIV infection and visceral leishmaniasis may have interact to lead to the clinical presentation of our patient.

Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.

OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

High mortality in peritonitis due to Mycobacterium avium complex: retrospective study and systematic literature review.

BACKGROUND: Mycobacterium avium complex (MAC) infection is often disseminated and mainly involves lymph nodes, spleen, liver or bone marrow. Peritonitis due to MAC infection (PMAC) is a very uncommon manifestation. METHODS: In this report, after describing the case of the only PMAC infection in our 10-year retrospective study, which occurred in an AIDS patient who was non-adherent to highly active antiretroviral therapy (HAART), we performed a systematic literature review of documented bacteriological PMAC. RESULTS: Including our patient, 51 cases of PMAC have been reported. Patients were most often male (sex ratio 2.14), with a median age of 41 years (2.8-72) and an immunodeficiency in all cases, most often AIDS (57%), cirrhosis (20%) and continuous ambulatory peritoneal dialysis (CAPD) (18%). Ascites was more often chylous (54%) than exudative (46%) and, in this case, lymphocytic (60%), with an inconstantly positive acid-fast bacilli smear (54%). Non-disseminated PMAC patients were more likely to have peritoneal dialysis (39% versus 6.5%, p < .01) or cancer with immunosuppressive therapy (39% versus 0%, p < .0001), while AIDS was the leading underlying disease in disseminated-PMAC patients (83% versus 11%, p < .001). Mortality was high (50%), with no difference between disseminated and non-disseminated PMAC. CONCLUSIONS: This report highlights the need to be aware of an atypical presentation of PMAC infection, which is associated with a high rate of mortality even for non-disseminated infection.

Immune Reconstitution Inflammatory Syndrome Unmasking or Worsening AIDS-Related Progressive Multifocal Leukoencephalopathy: A Literature Review.

Incidence of progressive multifocal leukoencephalopathy (PML) in HIV-infected patients has declined in the combined antiretroviral therapy (cART) era although a growing number of acquired immunodeficiency syndrome (AIDS)-related PML-immune reconstitution inflammatory syndromes (PML-IRIS) have been published during the same period. Therapeutic management of PML-IRIS is not consensual and mainly relies on corticosteroids. Our main aim was, in addition to provide a thoughtful analysis of published PML-IRIS cases, to assess the benefit of corticosteroids in the management of PML-IRIS, focusing on confirmed cases. We performed a literature review of the 46 confirmed cases of PML-IRIS cases occurring in HIV-infected patients from 1998 to September 2016 (21 unmasking and 25 paradoxical PML-IRIS). AIDS-related PML-IRIS patients were mostly men (sex ratio 4/1) with a median age of 40.5 years (range 12-66). Median CD4 T cell count before cART and at PML-IRIS onset was 45/µl (0-301) and 101/µl (20-610), respectively. After cART initiation, PML-IRIS occurred within a median timescale of 38 days (18-120). Clinical signs were motor deficits (69%), speech disorders (36%), cognitive disorders (33%), cerebellar ataxia (28%), and visual disturbances (23%). Brain MRI revealed hyperintense areas on T2-weighted sequences and FLAIR images (76%) and suggestive contrast enhancement (87%). PCR for John Cunningham virus (JCV) in cerebrospinal fluid (CSF) was positive in only 84% of cases; however, when performed, brain biopsy confirmed diagnosis of PML in 90% of cases and demonstrated histological signs of IRIS in 95% of cases. Clinical worsening related to PML-IRIS and leading to death was observed in 28% of cases. Corticosteroids were prescribed in 63% of cases and maraviroc in one case. Statistical analysis failed to demonstrate significant benefit from steroid treatment, despite spectacular improvement in certain cases. Diagnosis of PML-IRIS should be considered in HIV-infected patients with worsening neurological symptoms after initiation or resumption of effective cART, independently of CD4 cell count prior to cART. If PCR for JCV is negative in CSF, brain biopsy should be discussed. Only large multicentric randomized trials could potentially demonstrate the possible efficacy of corticosteroids and/or CCR5 antagonists in the management of PML-IRIS.

A Pilot Study of Tobacco Screening and Referral for Smoking Cessation Program among HIV-Infected Patients in France.

BACKGROUND: The prevalence of tobacco smoking is high among patients living with HIV, supporting the need for effective targeted interventions. MATERIALS AND METHODS: All current smokers at our outpatient HIV clinic were invited to participate in a smoking cessation program. RESULTS: Of the 716 patients living with HIV, 280 (39%) reported active smoking and were younger, more recently HIV infected and more frequently infected due to intravenous drug use (IDU). One hundred forty-seven (53%) smokers agreed to participate in the smoking cessation program and had a higher Fagerström score and were less likely IDU. During follow-up, 41 (28%) smokers withdrew from the program. After 6 months, 60 (57%) of the 106 smokers who completed the intervention had stopped tobacco smoking and were more likely to use varenicline, adjusting for a history of depression. CONCLUSION: Our smoking cessation program was feasible. However, strategies to reach and retain in smoking cessation program specific groups such as IDU are needed to improve the smoking cessation cascade.

Neurotoxocariasis: a systematic literature review.

PURPOSE: Toxocariasis is a widespread zoonosis, which may result in central nervous system injury. METHODS: We conducted a systematic literature review in MEDLINE, SciELO, ScienceDirect and Google Scholar up to April 2015 using a combination of the following search terms: "neurotoxocariasis" or "neurotoxocarosis", "toxocariasis" or "toxocarosis" and "cerebral" or "neurologic". RESULTS: One hundred cases of neurotoxocariasis were identified in literature. The majority of patients were male (58 %), with a median age of 42 years. The predominant clinical pictures were myelitis (60 %), encephalitis (47 %) and/or meningitis (29 %). Fever was inconstant (23 %). The suspected mode of transmission, mentioned in only 49 % of cases, was mainly contact with dogs and/or cats (67 %) and ingestion of contaminated food (31 %). Diagnostic imaging examinations found hypodense lesions in cerebral scanner sequences and hyperintense lesions in cerebral MRI T2-weighted sequences in 65 and 57 % of encephalitis cases respectively, and in 92 % of myelitis cases in medullary MRI T2-weighted sequences. The detection of antibodies against Toxocara spp. was almost constant in blood and cerebrospinal fluid (CSF), 99 and 93 %, respectively. The two most commonly used drugs were corticosteroids (72 %) and/or albendazole (68 %) for a period of at least 3 weeks, which often needed to be repeated. Despite a low mortality rate (6 %), complete remission was observed in only 40 % of cases. CONCLUSIONS: Neurotoxocariasis, a completely preventable zoonosis, could lead to severe sequelae failing prompt diagnosis. A compatible clinical picture, presence of risk factors, blood eosinophilia and high titers of antibodies against Toxocara spp. in CSF should alert physicians.

Study on daptomycin use and implementation of an antimicrobial stewardship program.

BACKGROUND: Treatment of Gram-positive pathogens remains a major health issue due to the presence of methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus spp. Daptomycin offers an alternative after therapeutic failure using glycopeptides. Yet its use requires strict control given its financial impact and environmental risks. Since 2014, the use of daptomycin within our hospital has intensified, occasionally outside the scope of its approved indications. OBJECTIVES: The aim of this study is to analyze the appropriateness of daptomycin prescriptions. SETTING: This work was conducted in a 1500-bed University Hospital. METHOD: A descriptive retrospective study was conducted from November 2013 to July 2014. All patients having received at least 2 days of treatment were included. Analysis of the appropriateness of daptomycin prescriptions was conducted by a multidisciplinary team comprised of infectious diseases specialists, pharmacists and a microbiologist. The appropriateness of daptomycin prescriptions was established based on Infectious Diseases Society of America recommendations published in 2011. MAIN OUTCOME MEASURES: The indicators chosen to determine appropriateness of prescription were: treatment indication, prescribed dose and other antibiotics associated with the daptomycin prescription. RESULTS: 19 patients (14 men/5 women) were included. Observed indications were: bone and joint infection (n = 6; 32 %), infectious endocarditis (n = 5; 26 %), bacteremia (n = 5; 26 %) and complicated skin and soft tissue infection (n = 3; 16 %). Identified pathogens were: MRSA (n = 14; 74 %), methicillin-resistant coagulase-negative Staphylococcus (n = 4; 21 %) and Streptococcus mitis (n = 1; 5 %). Daptomycin was prescribed as first-line treatment in 32 % of cases (n = 6). The mean dosage was 9 mg/kg/day (5-11 mg/kg/day) for a mean duration of 11 days (2; 55 days). Clinical success was observed in 42 % of cases (n = 8). Appropriateness for daptomycin use was only established for 15 % of prescriptions (n = 3). CONCLUSION: Faced with a lack of recent recommendations on the subject, our multidisciplinary team issued a local consensus, defining the indications and dosage modalities for this reserve antibiotic. This multidisciplinary approach enables improved use of recent anti-MRSA drugs.

Incidence of herpes zoster in HIV-infected adults in the combined antiretroviral therapy era: results from the FHDH-ANRS CO4 cohort.

BACKGROUND: Recent studies have shown a decrease in the incidence of herpes zoster (HZ) among human immunodeficiency virus (HIV)-infected patients since the combined antiretroviral therapy (cART) era, but more data are needed on a possible increase in the risk early after cART initiation. METHODS: We studied HZ incidence and risk factors among patients followed in the French Hospital Database on HIV (FHDH) between 1992 and 2011. Standardized incidence ratios (SIRs) were used for comparison with the general population between 2005 and 2008. The risk of HZ following cART initiation (0-5 and ≥6 months) was studied with Poisson regression models. RESULTS: A total of 7167 cases of incident HZ were diagnosed among 91 044 individuals (583 125 person-years [PY]). The incidence declined significantly, from 2955 per 100 000 PY in 1992-1996 to 628 per 100 000 PY in 2009-2011. This decline was mainly explained by cART (relative risk [RR], 0.60; 95% confidence interval {CI}, .57-.64). The risk of HZ was associated with low CD4 cell counts, high HIV RNA levels, low CD4/CD8 ratios, and prior AIDS. Compared to the general population, the risk of HZ was higher in HIV-infected patients (overall SIR, 2.7; 95% CI, 2.6-2.9), particularly those aged 15-44 years (SIR, 4-6). In ART-naive patients, a moderate increase in the HZ risk was observed during the first 6 months of cART, with a peak at 3 months (RR, 1.47; 95% CI, 1.26-1.73), a finding that disappeared after adjustment for the current CD4 cell count (RR, 1.03; 95% CI, .81-1.32). CONCLUSIONS: The risk of HZ has declined markedly among HIV-infected patients in the cART era, but remains 3 times higher than in the general population. The risk increases moderately during the first 6 months of cART.

Antimicrobial stewardship and linezolid.

BACKGROUND: Since 2002, linezolid, the first representative of the oxazolidinone class, has been widely prescribed, sometimes outside of approved indications. However, several cases of clinical outbreaks due to linezolid-resistant organisms have been reported, and its relatively high cost represents an economic challenge for hospital settings. OBJECTIVES: The aim of this study was to assess the impact of different actions conducted by an antimicrobial stewardship team (AST) to control over-prescription of linezolid with regard to the defined daily dose (DDD) per 1,000 inhabitants per day. SETTING: This work was conducted in a 1,495-bed hospital from 2009 to 2013. An AST, gathering the departments of pharmacy, microbiology, and infectious diseases, assessed the pertinence of linezolid use and associated effect on the prescriber. METHOD: A retrospective study was conducted throughout 2009. Three different evaluations were prospectively carried out, each for 3 months, between 2011 and 2013. MAIN OUTCOME MEASURE: The indicators chosen to monitor the consumption of linezolid were the DDD per 1,000 inhabitants per day, which enabled a comparison to be made between hospitals from 2004 to 2012, and of the pertinence of its prescription by different departments. RESULTS: From 2009 to 2013, 239 patients were evaluated through three 3-month stages. Prescriptions were for off-label use in 45 % of cases. Prescriptions were considered appropriate in 60 % of cases. Unsuitable treatment was either modified or discontinued (62 and 38 % of cases, respectively). Mean duration of linezolid treatment was 8 days, i.e. below the national mean duration reported in the literature. To highlight the impact of action taken by the team, a consensual strategy to treat ventilator-acquired pneumonia was elaborated with principal prescribers. Throughout the study, the mean DDD per 1,000 inhabitants per day increased very slowly and was lower than the eleven other French hospitals, which were secondarily included in this study. CONCLUSION: The multidisciplinary approach that was adopted for therapeutic education and delivery control led to an improvement in the proper use of linezolid. Similar strategy should be extended to other antimicrobial agents, such as carbapenems, for which both cost and risk of resistance emergence are of major concern.

Draft Genome Sequence of Campylobacter coli Strain IPSID-1 Isolated from a Patient with Immunoproliferative Small Intestinal Disease.

The genome sequence and annotation of Campylobacter coli strain IPSID-1 are reported here. This bacterial isolate is the first to be cultured from a patient with immunoproliferative small intestinal disease (IPSID). The draft genome sequence is 1.683 Mb long, comprises 64 contigs, and has 31.26% G+C content.

Complicated atazanavir-associated cholelithiasis: a report of 14 cases.

Fourteen human immunodeficiency virus (HIV)-infected patients receiving an atazanavir (ATV)-based antiretroviral regimen developed complicated cholelithiasis. ATV was found in biliary calculi in 8 of 11 cases: infrared spectrometry analysis of calculi revealed that ATV made up a median of 89% (range, 10%-100%) of the total calculus composition. Development and management of ATV-associated cholelithiasis are discussed.

Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication.

Consecutive missed doses may differentially impact the efficacy of antiretroviral therapy associated with the use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI). In a cohort of 72 subjects receiving a boosted PI, average adherence to dosage was a better predictor of human immunodeficiency virus (HIV) replication than was the duration or frequency of treatment interruption. In contrast with an NNRTI, consecutive missed doses of a boosted PI did not emerge as a major risk factor for HIV replication.

[Smoking cessation counseling center in a French hospital: Effectiveness at one year and predictors of outcome]. / Efficacité à 1 an et facteurs prédictifs d'échec d'une consultation hospitalière d'aide au sevrage tabagique.

OBJECTIVE: To assess the effectiveness at 1 year of a hospital clinic providing individual management of persons seeking to stop smoking and the factors predictive of failure. METHODS: This prospective descriptive study included smokers seeking assistance at this hospital clinic over a 1-year period. This analysis excludes persons with schizophrenia and those who came only to a first consultation. Treatment methods were those recommended by the 1998 consensus conference: nicotine substitutes or slow-release bupropion, depending on the level of nicotine dependence, cognitive-behavioral therapy appropriate for smoking in all cases, and the prescription before cessation of a selective serotonin re-uptake inhibitor (SSRI) for patients with anxiety or depressive disorders. Assessment was based on patients' self-report at 3 months, 6 months and 1 year. RESULTS: Of 99 smokers who came for at least one consultation, 38 were excluded and 61 were considered in the analysis. At one year, 18 patients (29.5%) were still not smoking. Of the 43 patients who resumed smoking, 27 (63%) did so during the first three months after cessation. According to the multivariate analysis, only female sex (p = 0.0173) and early end to follow-up (p = 0.0023) were significantly associated with the risk of relapse at 1 year. CONCLUSION: The study confirmed the usefulness of specialized medical support over a one-year period and highlighted the difficulties of smoking cessation for women, who appear to need a new not yet invented approach. The other standard factors predictive of failure were not observed, possibly because of either the broad prescription of SSRIs in cases of anxiety- or depression-related comorbidity or the statistical limitations associated with the population size.

Regression of CD8+ pseudolymphoma after HIV antiviral triple therapy.

To our knowledge, we report the first case of improvement of HIV-associated cutaneous CD8(+) pseudolymphoma with highly active antiretroviral therapy. This favors the hypothesis of a reactive cutaneous infiltration by HIV-specific cytotoxic T cells in this disease.