Extensively drug-resistant bacteria: Which ethical issues?

OBJECTIVE: The increased bacterial resistance to antibiotics has now become a public health concern. How can we preserve the well-being of patients presenting with infections caused by extensively drug-resistant bacteria (EDRBs) and that of their contacts without inducing any loss of chance of survival, all the while living together and controlling the spread of these EDRBs? METHOD: Terre d'éthique, a French territorial ethics committee, was asked to reflect on this topic by the infection control unit of a French University Hospital as it raises many ethical issues. RESULTS: Patients are at the core of any ethical approach, and respecting their autonomy is fundamental. Patients should be adequately informed to be able to give consent. Indeed, the creation and dissemination of a register (list of names of contacts or infected patients) entails responsibility of the infected person and that of the community. This responsibility leads to an ethical dilemma as protecting the group (the whole population) necessarily means limiting individual freedom. The principle of autonomy should thus be compared with that of solidarity. Is medical confidentiality an obstacle to the sharing of information or lists of names? CONCLUSION: We did not aim to answer our problematic but merely wanted to show the complexity of EDRB spread in a broader societal and economic context, all the while respecting the rights of patients.

[Hypertriglyceridemia-induced pancreatitis in pregnancy. A case report]. / Pancréatite aiguë secondaire à une hypertriglycéridémie majeure d'origine gestationnelle. A propos d'un cas.

We report the case of a 31-year-old pregnant patient in the 33rd week of gestation, with no history of dyslipidaemia, admitted for sub-acute epigastric pain. The milky aspect of blood samples was remarkable. Blood analysis showed a moderate increase in pancreatic enzymes but a major hyperlipaemia: triglyceridaemia 113 g/l and total cholesterolaemia 25 g/l. We suspected a hypertriglyceridemia-induced pancreatitis in pregnancy. The diagnosis was confirmed by CT-scan. Abdominal echography showed no abnormalities in biliary duct. After few hours, a caesarean was performed for acute fetal distress. The patient was admitted to the intensive care unit where a decrease of hypertriglyceridemia was already observed. Only one plasmapheresis was performed. Heparin was introduced. Rapid clinical improvement allowed discharge from intensive care at day 3. This case report illustrates lipid decrease with undertaken treatments. We discuss the management of hypertriglyceridemia-induced pancreatitis in pregnancy.

Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1 R and ecNOS.

BACKGROUND: Arterial hypertension (HT), secondary to cyclosporine A (CsA) used as main immunosuppressive treatment in renal transplantation (RTx), is very frequent (70%), usually severe and explained mostly by vasoconstriction of the glomerular afferent arteriole with secondary sodium and water retention. MATERIAL AND METHODS: In a retrospective study, we have analyzed 294 consecutive recipients receiving a first renal cadaveric allograft and all treated with CsA (the majority with triple therapy). We studied, by molecular biology, the polymorphism of genes previously implicated in essential HT such as: angiotensin-converting enzyme (ACE: II, ID and DD), angiotensinogen (AGT: MM, MT and TT), angiotensin II type 1 receptor (AT1-R: AA, AC and CC) and endothelial constitutive nitric oxide synthase (ecNOS: aa, ab and bb), and correlated the data to the prevalence and severity of post-Tx HT. This cohort included 195 (66%) males and 99 females with a mean age of 42 years at time of Tx. The presence and severity of post-Tx HT were indicated by initial persistent blood pressure over 140/90 mmHg with the need for at least one anti-hypertensive drug and by the number of anti-HT medications required to achieve its control. RESULTS: The distribution of the specific alleles and genotypes for ACE, AGT, AT1-R, and ecNOS was not different in transplant recipients compared to 181 controls. At 5 years post-Tx, the prevalence of HT was 72% (169 out of 235) among functioning grafts. There was no significant difference for ACE, AGT, AT1R and ecNOS genotypes distribution between hypertensive vs non-HT recipients. The number of anti-hypertensive drugs prescribed was not different among ACE, AGT, and AT1-R genotypes. However, the a allele and the non-bb genotype (aa + ab) for ecNOS were significantly (p = 0.001) associated with a less severe HT, needing fewer anti-HT drugs. At 10 years post-Tx, the HT prevalence remained high 78% (67 out of 86) among functioning Tx. However, the limited numbers did not allow further correlation. CONCLUSIONS: This study produced mainly negative results except for ecNOS-a allele, which seems to protect against severe hypertension. The explanation remains speculative but probably relates to the known cyclosporine-induced upregulation of ecNOS gene and enzyme activity.

Contribution of ultrasonography and cholescintigraphy to the diagnosis of acute acalculous cholecystitis in intensive care unit patients.

OBJECTIVES: To assess the respective value of ultrasonography (US) and morphine cholescintigraphy (MC) in the diagnosis of acute acalculous cholecystitis (AAC). DESIGN AND SETTING: Prospective study in an intensive care unit of a university hospital. PATIENTS AND INTERVENTION: Twenty-eight patients with clinically and biologically suspected of AAC. US was performed at the bedside and less than 12 h later MC. US was considered positive if three major criteria were present: wall thickness greater than 4 mm, hydrops, sludge; MC results were regarded as positive if the gallbladder could not be visualized. These latter patients underwent cholecystectomy and the diagnosis of AAC was confirmed through histopathological study. MEASUREMENTS AND MAIN RESULTS: Sensitivity of US and MC, respectively, was 50% and 67%, specificity 94% and 100%, positive predictive value 86% and 100%, negative predictive value 71% and 80%, and accuracy 75% and 86%. The correlation between US and MC findings was 71%, with chi = 0.31. By Bayesian analysis the probability of disease if the MC finding was positive was 100% regardless of US results. A positive US finding was associated with a 86% probability of disease, but with a probability of only 66% in case of negative MC results. MC is thus superior to US for confirming AAC in selected critically ill patients. Nevertheless, US is an easy, noninvasive, and effective method of bedside screening. The combination of the two imaging tests improves diagnostic accuracy and reduces false-positive and false-negative rates. Poor agreement between the two tests leads to better diagnostic complementarity.

A randomized prospective study comparing low-dose OKT3 to low-dose ATG for the treatment of acute steroid-resistant rejection episodes in kidney transplant recipients.

Acute steroid-resistant rejection episodes in kidney allograft recipients require treatment with antilymphocyte antibodies. Monoclonal anti-CD3 and polyclonal antilymphocyte antibodies have been widely used but seldom compared. Recent data have suggested that these antibodies could be used at reduced doses without jeopardizing their efficacy. In this study, we randomized renal transplant recipients who encountered a first acute steroid-resistant rejection episode to low-dose ATG or low-dose OKT3 treatment. Sixty patients were enrolled in the study. They received prophylactic immunosuppression with cyclosporin, azathioprine, and prednisolone. Treatment of biopsy-proven rejection consisted of a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was 484 +/- 110 mg, i.e., 0.75 mg/kg per day. The total OKT3 dose was 32 +/- 4 mg, i.e., 0.05 mg/kg per day. We compared reversion of rejection, side effects, immunodepression, and graft function. Reversion of rejection was similar in the two groups, although we noted a trend in favor of ATG. Results were 3% vs 10% early graft failures, 13% vs 23% overall graft failures, 28% vs 38% 3-month actuarial incidence of rebound rejection, and 89% vs 81% 1-year graft survival rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3 group due to the first-dose syndrome. Infections and cancers occurred with the same frequency. ATG resulted in a deeper and longer decrease in peripheral lymphocyte subsets. Graft function was similar in the two groups. We conclude that low-dose ATG and low-dose OKT3 are equally effective in reversing steroid-resistant acute rejection. Tolerance was better with ATG, which also gave a more potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3 did not appear to lessen their efficacy.

Advantage of antithymocyte globulin induction in sensitized kidney recipients: a randomized prospective study comparing induction with and without antithymocyte globulin.

BACKGROUND: Sensitized kidney allograft recipients require special management to improve their outcome. One strategy is heavy immunosuppression with antilymphocyte antibodies. Controversy continues about the actual advantage of induction protocols whilst infections and cancers are a constant risk. In addition, little is known about how to handle sensitized patients with low levels of sensitization. METHODS: In this study, we randomized sensitized renal transplant recipients, who received prophylactic treatment with or without antithymocyte globulin (ATG), in addition to a standard triple regimen consisting of cyclosporin, steroids and azathioprine at ATG discontinuation. The induction treatment consisted of a low-dose ATG course over 10 days. Randomization was stratified on the maximum PRA, according to the five following classes: 5% < PRA < or = 20%, 20% < PRA < or = 40%, 40% < PRA < or = 60%, 60% < PRA < or = 80% and 80% < PRA < or = 100%. RESULTS: Eighty nine patients were enrolled: 47 patients received ATG and 42 did not. ATG induction lowered the incidence of biopsy-proven acute rejection episodes from 64 to 38%, increased 1 year graft survival from 76 to 89% and was associated with a higher 1 year inulin clearance (37+/-15 vs 49+/-18 ml/min). ATG-associated side effects were restricted to leucopenia and thrombocytopenia, whereas bacterial and viral infections, gammopathies and cancers did not occur more frequently. ATG induction benefited all sensitized patients, and not only the hypersensitized patients. CONCLUSIONS: We conclude that ATG induction is beneficial for all sensitized patients, regardless of their level of sensitization, with regard to acute rejection episodes, graft survival and graft function. Low-dose ATG is sufficient and prevents additional complications.

[Can one graft with a positive cross-match?]. / Peut-on greffer avec un cross-match positif?

Differential cross-matches have been proposed to allow immunised patients to be grafted, whereas the dogma of a global positive cross-match discarded them from renal transplantation. We report our one-center experience considering current T positive cross-match as the only contra-indication to grafting, as well as patients whose sera comprise specific anti-donor antibodies. A comprehensive characterization of the antibodies was achieved by identification of auto-antibodies and specification of IgM and IgG isotype, class I and class II specificities, as well as HLA specificities. The differential cross-match comprised an auto and an allo-cross-match, against T and B lymphocytes. Historical and current sera were analysed either untreated or after DTT-treatment, at +4 degrees C and +22 degrees C. We performed 79 renal transplantations across positive cross-matches, which were 20 historical T positive cross-matches, 26 historical B positive cross-matches and 33 current B positive cross-matches. Results and graft survival were strictly identical as those obtained in the transplantations achieved with negative cross-matches throughout the same period, especially in sensitized patients. Current positive B cell cross-matches due to IgG were associated with an increased risk for early graft failure. We conclude that differential cross-match is a safe strategy permitting immunised patients to be grafted.

On-line continuous venovenous hemodiafiltration: a technique for the control of ultrafiltration and convection during continuous renal replacement therapy.

Continuous renal replacement therapies have been used increasingly in critically ill patients in nephrologic and intensive care units. These techniques are nevertheless time consuming and lack an easy control of ultrafiltration. We conducted continuous venovenous hemodialysis (CVVHD) on a dialysate delivery machine which ensures a volumetric control of ultrafiltration, and which produces both dialysate and infusate with the on-line technique. This new mode of CVVHD was firstly assessed in a feasibility study and was secondly used in a randomized prospective study whose goal was to establish the usefulness of convection. On-line continuous venovenous hemodiafiltration (OL-CVVHDF) appeared safe and time saving, and allowed the fine control of fluid management in critically ill patients. Convective transfers were achieved by a 2 L/h predilutional infusion and increased urea and creatinine clearances twofold. OL-CVVHDF revealed itself to be a valuable method for the control of ultrafiltration and for efficient convective transfers during CVVHD.