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Biomedical subjects

P M Roger

Publications and source records attributed to P M Roger.

At least 19 recordsLinked to original sources

In vitro selection of mutants of Streptococcus pneumoniae resistant to macrolides and linezolid: relationship with susceptibility to penicillin G or macrolides.

OBJECTIVES: To evaluate the rate of acquisition of resistance to linezolid and macrolides in Streptococcus pneumoniae isolates with different levels of susceptibility to penicillin and erythromycin. MATERIALS AND METHODS: Thirty strains of S. pneumoniae were tested by serial passages in subinhibitory concentrations of each antibiotic by the spiral method. The four copies of the 23S rRNA rrl gene of parent strains and linezolid-resistant mutants were amplified and sequenced. RESULTS: The rate of acquisition of macrolide resistance did not differ when C-14 and C-16 macrolides were tested. Resistance to linezolid in strains susceptible to penicillin and erythromycin was difficult to produce. For mutants with low-level resistance to linezolid the cut-off value of the MIC was between 6 and 8 mg/L depending on the strain. All linezolid-resistant mutants displayed a mutation in 2-4 copies of the 23S rRNA rrl gene, mainly the G2576U mutation (27/30) with an additional C2610U mutation observed in certain mutants. Two new mutations were also noted, namely C2612A and C2571G. In three linezolid-resistant mutants no mutation was identified within the studied domain, suggesting another mechanism of resistance. CONCLUSIONS: Linezolid resistance in pneumococcal strains susceptible to penicillin and macrolides was more difficult to obtain than with macrolides. Increased resistance to these agents may therefore influence the clinical use of linezolid.

Acetamides↗

Relevance and complications of intravenous infusion at the emergency unit at Nice university hospital.

OBJECTIVE: Insertion of peripheral venous catheters (PVCs) is current practice within the hospital environment and particularly in the emergency department (ED). This simple yet invasive technique may result in venous thrombosis, infection or mechanical complications. We conducted a prospective study at the Nice University Hospital ED in order to determine the frequency, relevance and complications of peripheral venous cannulation. PATIENTS AND METHODS: Fourteen 24 h periods were surveyed over the months of May and June 2000, during which 2515 patients over 16 years of age attended the unit. Demographic and medical data were recorded for every patient who received a PVC. These patients were followed at 12 h intervals until the catheter was removed. Reasons for PVC, time left in place, and eventual complications were recorded. Justification for PVC was evaluated upon arrival at the ED, upon exiting the ED and in some cases within the hospital ward. RESULTS: Six hundred and thirty of 2515 patients (25%) received a PVC (290 women (46%) and 340 men (54%); meanage 58 years). Indication for the PVC was considered unjustified in 24.8% of cases upon arrival at the ED, and 33.8% upon leaving the ED. Upon admission in a hospital ward after passing through the ED, out of 318 patients, the PVC was left in place for no reason in 63 (20%). Overall, 390 PVCs were followed until the time of their removal. Mean duration of IV infusion was 28 h. Among these 390 patients, 62 (15.9%) developed complications, of which 54 (13.6%) had thrombophlebitis and 9 (2.3%) developed local infection. Mean duration of PVC left in place for patients with complications was 50 h vs 25 h for patients with no complications (P<0.001). CONCLUSION: Insertion of a PVC is common practice especially in EDs. The excessive use of this procedure leads to extra cost and iatrogenic complications. A renewed definition of its indication and raised awareness among hospital staff concerning the risks involved with this standard procedure should result in less use of PVC and fewer complications.

Catheterization, Peripheral↗

[Motives for the prescription of antibiotics in the emergency department of the University Hospital Center in Nice. A prospective study].

OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation in the emergency unit of the University Hospital in Nice. Unjustified antiobiotherapy is often initiated. We therefore conducted a survey to study the motives and validity of antibiotic prescriptions. METHOD: This prospective study was conducted in two phases. The first consisted in asking the emergency physicians prescribing antibiotics to fill-in a questionnaire giving information on the diagnosis established and the antiobiotherapy proposed. In the second phase, the diagnoses and corresponding treatments were submitted to 4 experts who assessed the acceptability of the diagnoses and the antibiotics prescribed. The experts only had access to the clinical and para-clinical data available. Moreover, their therapeutic judgement was based on previously published consensuses. RESULTS: The 6-month survey collected 117 questionnaires that could be analysed. The rate of error in diagnosis was of 33% (39/117). Thoracic x-rays could not be interpreted in 11% of cases. In single variant analysis, factors of erroneous diagnosis were due to its interpretation by an internist, the diagnostic category of "broncho-pulmonary infections" and the lack of documentation. In multi variant analysis, only the lack of documentation was related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002). The rate of antibiotherapy not adapted to the diagnosis made by the physician was of 32% (37/117). In 24 cases the modalities of the prescription were incorrect and in 13 cases the prescription was unjustified. Only the status of the prescriber (internist) was statistically associated with an antibiotherapy not adapted to the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05). CONCLUSION: Unjustified antibiotherapy in an emergency unit is generally due to erroneous diagnosis of infection. The lack of documentation and inexperience of the prescribers appear to be the two elements contributing to unjustified antibiotherapy.

Anti-Bacterial Agents↗

[Thrombotic microangiopathy during HIV infection. A retrospective study performed in infectious diseases units in southern France].

OBJECTIVES: To describe and analyze the clinical and biological manifestations of thrombotic microangiopathy (TMA) and evaluate the therapeutic strategies. METHODS: A retrospective study was performed in 14 infectious diseases units of southern France. All HIV patients presenting TMA during the last decade were selected (n = 14). RESULTS: The principle signs observed, aside from defining TMA (association of microangiopathic hemolytic anemia, thrombocytopenia and renal failure), were diarrhea (n = 9) and a high level of lacticodehydrogenase (LDH). Patients were at an advanced stage of HIV infection (median of CD4+ cells counts = 70/mm3). Specific etiology was identified in 7 cases: bacterial infection (n = 5), CMV retinitis associated with Kaposi's sarcoma (n = 1) and intravenous drug use (n = 1). Various treatments were used: plasmatic exchange (5 cases), fresh frozen plasma (6 cases), steroid therapy (4 cases), acetyl salicylic acid (3 cases), adaptation of antiretroviral treatment (3 cases). The global prognostic was poor with 50% mortality within 2 months. A high level of LDH (> 2500 UI/L) was associated with premature death in 5 of the 6 cases observed. CONCLUSION: Our data confirm the severity of TMA in case of HIV infection. The common treatment remains the use of plasmatic exchange and fresh frozen plasma; an optimal antiretroviral therapy must be associated.

AIDS-Related Opportunistic Infections↗

Infection of mice with Mycobacterium avium primes CD8+ lymphocytes for apoptosis upon exposure to macrophages.

Mycobacterial infection is associated with granuloma formation in which the presence of apoptosis has been recognized. The role of CD4+ T and CD8+ T cells in host protection against mycobacterial infections has been demonstrated. Previous studies, however, have shown that CD8+ T cells have a limited role in host defense against Mycobacterium avium infection, and we hypothesize that M. avium infection could lead to T cell apoptosis. To investigate this hypothesis, C57BL/6 mice were infected with M. avium strain 101, and the rate of apoptosis of splenic lymphocytes cultured ex vivo with peritoneal macrophages was determined and compared with that of controls. When exposed to infected macrophages ex vivo, splenic lymphocytes from M. avium-infected mice underwent apoptosis, as determined by the TUNEL assay. This increased T cell apoptosis above the control level was observed after 3 weeks but not after only 1 week of infection in mice. No splenic T cell apoptosis was observed when lymphocytes from Mycobacterium smegmatis-infected mice were cultured in the presence of M. smegmatis-infected peritoneal macrophages. Likewise, macrophages infected in vitro with heat-killed M. avium did not trigger T cell apoptosis. Culture of macrophages in different chamber from lymphocytes, separated by a transwell membrane, was not associated with increase of apoptosis compared with uninfected control, suggesting a requirement for direct cell-cell interactions to trigger lymphocyte apoptosis. Using a double staining TUNEL followed by anti-mouse CD4 or anti-mouse CD8 monoclonal antibodies, it was observed that only CD8+ T cells but not CD4+ T cells underwent apoptosis at 3 weeks of infection. In conclusion, M. avium infection in C57/BL6 mice for 3 weeks renders CD8+ T cells prone to apoptosis when exposed ex vivo to macrophages infected with M. avium.

Animals↗

[Evaluation of a hospitalization unit opened during the winter influenza epidemic of 1999-2000].

PURPOSE: Last winter, a great many patients with influenza-like infection were admitted to our hospital, leading us to open a specific unit for 6 weeks. We report the evaluation of medical care given to these patients. METHODS: Useful data for evaluating care to patients presenting respiratory infections were determined beforehand by the retrospective analysis of patients' charts. RESULTS: Fifty-seven out of 185 admitted patients (31%) had infectious respiratory symptoms. The mean age was 81 years. Six cases of influenza virus infection, 43 cases of viral bronchitis, six cases of bacterial pneumonia, one superinfected asthma and one septic shock were diagnosed. All patients presented with cardiac and/or chronic pulmonary diseases. Influenza vaccination had been performed in 28 patients (49%). Before hospitalisation, 30 patients (52%) had received antibiotics, and 17 (30%) a steroid therapy. In contrast, only 12 patients (21%) have received anti-infective agents during the hospitalisation. Twenty-five patients were able to go back home and a nursing home was required for 27 patients (47%); five patients died. Tools for improving this specific department in a public hospital are discussed. CONCLUSION: Vaccinations in the elderly appear to be poorly utilized; meanwhile, antibiotic treatments, as well as steroid therapy, are overused. Managing epidemic infections requires attention from the public hospital system.

Aged↗

How to organise antibiotic prescription.

In recent years, efforts have been made in hospitals to improve antibiotic prescription. Most universities organise courses on the subject, which lead to a local university diploma. However, possessing such a diploma does not give entitlement to prescribe. In fact, most doctors prescribe antibiotics and such courses are only of interest to volunteer physicians. While some are very careful, the majority prescribe the drugs as they are rarely toxic. Others are refractory to any information and particularly to any training. Two methods are typically proposed to reduce unjustified prescription. As a result of imposed restrictions, only trained doctors having met the training standards are allowed to prescribe and have to keep to a limited budget. The persuasive method, on the other hand, opens the way for a wide scope of training courses, which are provided by industry; some are said to be biased as they encourage prescription and the risk of selecting resistant mutant bacteria is scarcely documented. This method does not always coincide with the training curricula. The industry is torn between declared objectives such as judicious drug use and prevailing commercial aims. As a result, prescription is not restrained by any objective limit. It should be noted that prescription varies greatly from one hospital to another and within a given hospital between one department and another. Certain departments prescribe much more than others and these (emergency, medical and surgical intensive care, respiratory disease) should be targeted first.

Anti-Bacterial Agents↗

Effect of beta-lactam antibiotics on the in vitro development of resistance in Pseudomonas aeruginosa.

OBJECTIVE: To investigate whether stepwise selection of resistance mutations may mirror the continued bacterial exposure to antibiotics that occurs in the clinical setting. METHODS: We examined the in vitro development of resistance to a number of commonly used antibiotics (cefepime, cefpirome, ceftazidime, cefotaxime, piperacillin and imipenem) in Pseudomonas aeruginosa, a significant nosocomial pathogen. Stepwise resistance was assessed by serial passage of colonies located nearest to the inhibition zone on antibiotic-containing gradient plates. RESULTS: The lowest frequencies of spontaneous resistance mutations were found with cefepime and imipenem; these drugs also resulted in the slowest appearance of resistance of spontaneous resistance mutations. In five wild-type P. aeruginosa strains, cefepime-selected isolates required a mean of 30 passages to reach resistance; resistance occurred more rapidly in strains selected with other cephalosporins. P. aeruginosa strains that produced beta-lactamase or non-enzymatic resistance generally developed resistance more rapidly than wild-type strains. For most strains, resistance to all antibiotics except imipenem correlated with increased levels of beta-lactamase activity. Cross-resistance of cephalosporin-selected resistant mutants to other cephalosporins was common. Cephalosporin-resistant strains retained susceptibility to imipenem and ciprofloxacin. CONCLUSIONS: From our in vitro study, we can conclude that the rate of development of resistance of P. aeruginosa is lower with cefepime compared with other cephalosporines.

Anti-Bacterial Agents↗

Ventricular patch endocarditis caused by Propionibacterium acnes: advantages of gallium scanning.

Propionibacterium acnes is a weakly pathogenic commensal of the skin. When isolated from blood cultures it is often considered a contaminant. However, P. acnes may be responsible for severe infections and its role in certain cases of infectious endocarditis has now been definitely established.(1) We report a case of endocarditis due to P. acnes stemming from a ventricular patch and revealed by a gallium 67 scan.

Endocarditis, Bacterial↗

Longterm survival in acute rhinocerebral mucormycosis with giant cell arteritis and foreign body granulomas.

A case of rhinocerebral mucormycosis occurring in a 41-year-old man with insulin-treated diabetes mellitus is reported. Microscopically, biopsy samples obtained from the left ethmoid and middle turbinate sinuses contained fungi that formed mycotic granulomas associated with multinucleate giant cell arteritis. The multinucleate giant cells contained broad, infrequently septate hyphase consistent with mucormycosis. The patient received surgical debridement with extenteration of the left orbit, and intravenous liposome-encapsulated amphotericin B. After 12 months, examination of the patient revealed complete healing. Multinucleate giant cell granulomas and arteritis are only exceptionally associated with rhinocerebral mucormycosis, but these histologic findings may be correlated with a progressive disease with better prognosis.

Acute Disease↗

Persistent viral load in patients on HAART is associated with a higher level of activation-induced apoptosis of CD4(+) T cells.

Apoptosis is one of the mechanisms involved in the persistent CD4(+) T cell lymphopenia occurring in human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART). The aim of this study was to look at the relationship between the level of T cell apoptosis in patients on HAART and their HIV viral load measurement. Forty-five patients receiving HAART for a median time of 5 months were included: 13 had an undetectable viral load and 32 had a viral load > or = 200 copies/mL. No relationship was observed between the level of spontaneous T cell apoptosis and the viral load measurement. Patients with a viral load > or = 200 copies/mL exhibited a significantly higher level of CD4-induced apoptosis of CD4(+) T cells, compared with patients with undetectable viraemia (38 versus 15%, respectively, P = 0.03). Activation-induced apoptosis may be involved in the paucity of the immune reconstitution observed in HIV-infected patients treated with HAART.

Adult↗

[Systematic infection consultation in the intensive care unit. Impact of short-term antibiotic use].

OBJECTIVES: Multiresistant bacteria are regularly isolated in nosocomial infections occurring in intensive care units due to wide use of antibiotics. We evaluated the impact of systematic infectiology consultations on the quality of antibiotic prescriptions in an intensive care unit. PATIENTS AND METHODS: Infectiology consultations (3 per week) were initiated mid February 1999. The infectiologist gave oral advice to be implemented (or not) by the intensive care unit according to ongoing therapeutic options. The hospital pharmacy recorded antibiotic use for March and April 1999 for comparison with use recorded in 1998 for a similar period. We retrospectively reviewed the files of patients hospitalized during these periods and who had received antibiotics to determine the modalities of antibiotic use. The 4 antibiotics used for the longest period for each patient were recorded. RESULTS: Thirty-one patients in 1999 and 30 in 1998 were given antibiotics. The SAPS score was similar for the two groups. Mean duration of antibiotic treatment was lower during the March-April 1999 period than during the corresponding period in 1998: 13 +/- 9 days/patient versus 23 +/- 21 days/patient respectively, p = 0.037. In 1998, there were 596 antibiotic-days and in 1999 there were 455 (-24%). The cost of antibiotic therapy in 1998 was 70,342 FrF compared with 56,804 FrF in 1999 (-19%). CONCLUSION: Infectiology consultation, in association with the opinion of the intensive care physician, is a simple way to limit antibiotic use.

Aged↗

[Recurrent infectious and metastatic cellulitis cause by Escherichia coli].

BACKGROUND: We report a case of recurrent and metastatic infectious cellulitis caused by Escherichi coli. CASE REPORT: A 79-year-old man with a history of alcoholic cirrhosis and a myelodyplasia syndrome was hospitalized for skin rash and inflammatory edema of the right leg associated with bullous and necrotic lesions. Culture of a bulla puncture fluid grew E. coli. A two-drug intravenous antibiotic regimen and surgical cleansing led to a favorable outcome in 3 weeks. One week after withdrawal of the antibiotics, the patient developed a recurrent erythematous and inflammatory lesion of the right flank. Blood culture grew E. coli. The intravenous antibiotics were reinitiated immediately and provided rapid regression of the skin signs. Search for a urinary or digestive tract neoplastic focus was negative. DISCUSSION: E. coli cellulitis is a very uncommon usually fatal condition. Clinicians should be aware of a possible association with alcoholic cirrhosis. In case of recurrence, it is important to search for a digestive, hepatobiliary or urinary tract focus. Broad spectrum empirical antibiotic therapy must be initiated rapidly. Surgery is required in case of necrotizing cellulitis whatever the infectious agent.

Aged↗

Medical treatment of a pacemaker endocarditis due to Candida albicans and to Candida glabrata.

We describe a case of pacemaker infection due to two fungal species: Candida albicans and C. glabrata. Transthoracic echocardiography showed a large vegetation on the intraventricular wires. Because of severe underlying diseases, surgery was believed to be contraindicated. The patient was treated using high dose of fluconazole, resulting in clinical improvement and negative blood cultures. However, 2 months later, the patient underwent a fatal stroke. At autopsy, a large vegetation was found only all along the wires. Postmortem culture of the infected material was positive for both C. albicans and C. glabrata.

Aged↗