Vancomycin-resistant enterococci with reduced daptomycin susceptibility in Singapore: prevalence and associated factors.

Prevalence of vancomycin-resistant enterococci (VRE) and use of daptomycin are increasing in Asia. To determine the prevalence of daptomycin non-susceptible enterococci (DNSE) and understand factors associated with reduced daptomycin susceptibility in VRE, we conducted a case-control study in a 1600-bed adult tertiary hospital in Singapore. All VRE isolates from inpatients in 2012 were tested for daptomycin susceptibility. Patients with VRE isolates of daptomycin minimum inhibitory concentration (MIC) ⩾3 µg/ml were classified as daptomycin-reduced susceptible VRE (DRS-VRE) and those with daptomycin MIC 4 µg/ml (DNSE). About half (135, 55%) had reduced susceptibility to daptomycin (MIC 3-4 µg/ml). None in the DS-VRE group had prior exposure to daptomycin. After adjusting for age, gender, comorbidity, hospitalization duration, surgical history, indwelling device use, and duration of antibiotic exposure in the prior 3 months, >1 movement between wards [odds ratio (OR) 0·35, 95% confidence interval (CI) 0·16-0·74, P = 0·006] and minocycline resistance (OR 0·45, 95% CI 0·25-0·84, P = 0·011) were independently associated with DRS-VRE. Our study suggests that daptomycin exposure, >1 movement between wards, and resistance to minocycline, were associated with reduced daptomycin susceptibility in VRE.

Reducing the incidence of TRALI in the UK: the results of screening for donor leucocyte antibodies and the development of national guidelines.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is associated with the passive transfusion of leucocyte antibodies in blood products. Blood Transfusion Services have adopted a number of different strategies for reducing the incidence of TRALI, but, while these have been successful, TRALI has not been completely eliminated. Many Transfusion Services have introduced leucocyte antibody screening of donors to further reduce TRALI. This report describes the results of donor leucocyte antibody screening within NHS Blood and Transplant and the guidelines that have been developed for Transfusion Services within the United Kingdom (UK) to reduce the incidence of TRALI. MATERIALS AND METHODS: Blood samples from newly recruited female apheresis donors were tested for human leucocyte antigens (HLA) class I and class II antibodies and granulocyte-specific antibodies. RESULTS: A total of 1157 female donors were evaluated. Three hundred and fifteen (27·23%) donors had HLA class I or II antibodies and were returned to red cell component donation. Fifty-seven (6·77%) of the remaining 842 donors were found to have granulocyte-specific antibodies of which 11 (1·31%) had HNA-specific antibodies. A total of 818 donors (70·70%) were accepted for platelet apheresis, 336 donors (29·04%) were returned to red cell component donation, and three donors with HNA-3a antibodies (0·26%) were deferred from therapeutic donation. CONCLUSIONS: Female donors with leucocyte antibodies were identified in a stratified screening programme. Donors with antibodies were either directed to red cell donation or deferred. This process, combined with other measures that have already been introduced, is anticipated to further reduce the incidence of TRALI.

Measurement of macrophage marker in hyperhaemolytic transfusion reaction: a case report.

BACKGROUND: Hyperhaemolytic transfusion reaction (HHTR) has been well described in patients with sickle cell disease (SCD). It is characterised by a decrease in haemoglobin concentration to levels below those before transfusion and a fall in the absolute reticulocyte count. As red blood cells (RBC) alloantibodies are typically not detected in post-transfusion samples in acute forms of HHTR, we have previously proposed that both the transfused and autologous RBCs cells (HbSS/reticulocytes) are destroyed by activated macrophages. CASE REPORTS: We report a patient with SCD who presented with vaso-occlusive sickle cell crisis and developed a severe HHTR attributable to anti-Fy3. In addition to the usual supportive measures, the patient was treated with intravenous immunoglobulin (IVIG) and steroids. Serum ferritin levels were measured as an aspecific marker of macrophage activation. RESULTS: Steroids and IVIG were effective in managing HHTR. Ferritin levels were high at the time of haemolysis, (>10000 µg L(-1)) whereas recovery and cessation of haemolysis correlated with a decrease in ferritin levels. CONCLUSION: Serum ferritin values >10,000 µg L(-1) are considered pathognomic for conditions characterised by abnormal macrophage activation. In our case, serum ferritin levels correlate well with the disease activity and clinical response. This further supports our previous proposal that the activated macrophages play an important role in HHTR. Serum ferritin is a nonspecific marker of inflammation. A rapid specific bio-marker to measure the activity of macrophages in SCD in HHTR is desirable, and this area warrants further investigation.

How much residual plasma may cause TRALI?

Although passive infusion of plasma-rich components containing white blood cell (WBC) antibodies are responsible for majority of the reported transfusion-related acute lung injury (TRALI) cases, the minimum volume of residual plasma, which might trigger TRALI, is not known. We report three cases of TRALI where the implicated donor component contained between 10 and 20 mL of residual plasma. Two cases were related to transfusion of red blood cells prepared in optimal additive solution, and the other was related to transfusion of pooled buffy coat platelets. In the latter case, WBC antibodies that matched the patient's human leucocyte antigen (HLA) antigens were only found in one buffy coat donor (female) who contributed a buffy coat for pooled platelets preparation. Plasma prepared from pooling platelets was collected from a male donor. Laboratory investigation confirmed that in all three cases, the donors' serum contained three to four different HLA class 1-specific and class 11-specific antibodies that matched with the patient's HLA type. Our cases suggest that the residual plasma volume as small as 10-20 mL containing donor derived WBC antibodies may cause TRALI. The risk of TRALI remains, despite providing pooled platelets suspended in male donor plasma. The significance of multiple HLA antigen/antibody matching between donor and recipient in immune TRALI warrants further study.

Management of pregnancy complicated by anti-hrB/anti-HrB.

Anti-hrB and anti-HrB are rare alloantibodies found predominantly in people of Black African descent. It has been assumed that strongly reacting examples of anti-hrB may cause hemolytic transfusion reactions, but precise information is limited. Anti-HrB is a clinically significant antibody and may cause hemolytic transfusion reactions and HDN. Selection of blood for transfusion support for patients with these alloantibodies, and especially with anti-HrB, imposes a special challenge in the United Kingdom. We report two antenatal patients (both patients were of the partial D phenotype DIII), one with anti-hrB, anti-Ce, and anti-D; the other,with anti-hrB and anti-D, who later formed anti-HrB. Transfusion support and the outcome of the pregnancies are discussed. A literature search confirms that,apart from some publications in abstract form,there is not much detailed clinical information available for either anti-hrB or anti-HrB. Further information and publications are warranted to gain more knowledge of these rare antibodies.

Trends in the expression of breastmilk 1993-2003.

The expression of breastmilk is an important strategy to enable mothers to continue exclusive breastfeeding. In some situations, for health or convenience, expressed breastmilk is required and infants fed this way still fall within the definition of exclusive breastfeeding. The aim of this study was to document the changes in rates of breastmilk expression between the first Perth Infant Feeding Study (PIFS I) in 1992-03 and PIFS II in 2002-03. The proportion of mothers expressing breastmilk peaked in the first six weeks, at 38% for PIFS I and 69% for PIFS II. The proportion of mothers who had expressed breastmilk had almost doubled in the decade between studies. The proportion of mothers expressing declined to about 28% of mothers at 22 weeks for PIFS II and slightly less in PIFS I. Breastmilk expression is a very useful skill to allow mothers to exclusively breastfeed until six months and should be taught to all mothers.

Autoimmune hemolytic anemia and a further example of autoanti-Kpb.

A 65-year-old Caucasian man with myelodysplasia was admitted with autoimmune hemolytic anemia and a Hb of 5.6 g/dL. The patient's serum contained anti-K; the DAT on the patient's RBCs reacted 3+ with anti-IgG and 3+ with anti-C3d. K- RBC units were transfused, but there was no sustained increase in Hb level. The samples were referred to the reference laboratory of the National Blood Service. The DAT results remained the same, with anti-K detected only in the serum. An eluate prepared from the patient's DAT-positive RBCs revealed anti-Kp(b) specificity. This study reports an unusual case of autoanti-Kp(b), which is different from previously published cases in that no free anti-Kp(b) was detectable in the serum.

Rapid cardiovascular action of aldosterone in man.

Rapid nongenomic in vitro effects of aldosterone have been demonstrated recently in cultured vascular smooth muscle and endothelial cells. But there is, as yet, little evidence for corresponding in vivo effects. The present study thus investigates the rapid nongenomic effects of aldosterone on human cardiovascular function. In a double-blind placebo-controlled randomized parallel trial on 17 patients with suspected coronary heart disease, the effect of 1 mg aldosterone iv on cardiovascular function was assessed during cardiac catheterization. Hemodynamic parameters (such as heart rate, left ventricular and atrial pressures, arterial pressures, vascular resistances, and cardiac output) were measured before and 3 and 10 min after administration of aldosterone or placebo. Significant changes were found for systemic vascular resistance, cardiac output, and cardiac index, compared with the placebo group (Wilcoxon test, P < 0.02-0.05). The effect of aldosterone dissipated within 10 min. The results are in line with the in vitro data cited above and consistent with earlier findings on acute cardiovascular effects of aldosterone, which have now been confirmed and extended by contemporary techniques. The hypotheses of rapid nongenomic in vivo effects of aldosterone are further substantiated by this study.

A new and potent calmodulin antagonist, HF-2035, which inhibits vascular relaxation induced by nitric oxide synthase.

HF-2035, 2-[N-(2-aminoethyl)-N-(2,4,5-trichlorobenzenesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, was synthesized and its effects on calmodulin-dependent enzymes were investigated. HF-2035 inhibited calmodulin kinase I, calmodulin kinase II and myosin light-chain kinase with IC50 values of 1.3 microM, 1.6 microM and 68 microM, respectively. HF-2035 also inhibited the activity of recombinant rat neuronal nitric oxide synthase, one of the calmodulin-dependent enzymes, with a Ki of 0.78 microM. Partially purified nitric oxide synthase of rat brain was also inhibited by HF-2035 with an IC50 of 3.2 microM. Kinetic analysis indicated that this inhibitory effect of HF-2035 was competitive with respect to calmodulin. We examined the effects of HF-2035 on constitutive nitric oxide synthase in a bioassay using vascular strips of rabbit carotid artery with and without endothelium. HF-2035 inhibited acetylcholine- and calcium ionophore, A23187 (6S-[6 alpha (2S*,3S*),8 beta (R*),9 beta, 11 alpha]-5- (methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol-2-yl)- ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-4-benzoxazol ecarboxylic acid)-induced relaxation of endothelium-intact strips with an ED50 of 1.5 +/- 0.5 microM and 2.8 +/- 1 microM, respectively. This compound, however, did not inhibit N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A), an exogenous nitric oxide donor, -induced relaxation of endothelium-denuded strips. W-7 (N-(6-aminohexyl)-5-chloro-1- naphthalenesulfonamide) inhibited acetylcholine-induced relaxation with an ED50 of 46 +/- 7 microM, which was 30-fold less potent than HF-2035. HF-2035 was unable to inhibit the activity of the inducible form of nitric oxide synthase in isolated thoracic aorta of rat treated with Escherichia coli lipopolysaccharide. These findings suggest that HF-2035 is a new and potent calmodulin antagonist, and may be used as a mother compound to develop more selective inhibitors of constitutive nitric oxide synthase.

High prevalence of hepatitis C in patients with thalassemia and patients with liver diseases in Myanmar (Burma).

We conducted Myanmar-Japan cooperation studies on hepatitis B and hepatitis C virus markers in patients with thalassemias and those with liver diseases. Among the 102 patients with liver diseases, 92% had a history of hepatitis B virus infection (antibody to hepatitis B core antigen positive), 35% were hepatitis B surface antigen positive, 39% were positive for anti-HCV. Among 28 patients with hepatocellular carcinoma, 46% had hepatitis B surface antigen, 21.4% had antibody to hepatitis C virus, and 7% were positive for both hepatitis B surface antigen and anti hepatitis C virus. The history of HCV infection among blood recipients at the Haematology Department of the Yangon General Hospital and at the Yangon Children's Hospital was found to be 55.5% and 46.7%, respectively, which is comparable to the history of hepatitis B infection (66.7% and 46.7%, respectively). This preliminary survey also encountered 2 cases positive for anti-HCV among 34 voluntary blood donors. This survey is the first one to report that hepatitis C is at the epidemic stage in Myanmar. As there is no effective treatment for hepatitis C in this country, a screening program for blood used in transfusion should be started immediately.

Brain laryngeal mask--study in 50 spontaneously breathing patients.

Brain laryngeal mask (BLM) was used to assess its suitability in 50 spontaneously breathing patients by one lecturer and 4 Medical Officers. Insertion of the laryngeal mask was successful at the first attempt in 42 patients, second attempt in 7 and third attempt in one. The incidence of airway obstruction secondary to downfolding of the epiglottis, which was corrected by reinsertion, was 16%. Post-operative complications included clenching of teeth in 5 patients, vomiting in 2 and excessive salivation in 3. The incidence of sore throat was 10%.

Comparison of two bolus doses of esmolol for attenuation of haemodynamic response to tracheal intubation.

This prospective study was designed to compare the effectiveness of esmolol (either 100 mg or 200 mg) with a placebo in blunting the haemodynamic response to laryngoscopy and intubation. Seventy-five patients of ASA I or II scheduled for routine-surgery were selected and entered into a placebo-controlled study. Patients were randomly allocated to receive placebo, 100 mg or 200 mg of esmolol IV as part of an anaesthetic induction technique. There were no significant differences in the demographic distribution of the patients in the study. There was no statistical difference in the baseline heart rate (HR) and systolic blood pressure (SBP) between the three groups. One minute after the administration of the drug (prior to intubation) the differences in HR between the placebo group and both the 100 mg and 200 mg groups were significant (p < 0.05), and also at 1 min and 2 min following intubation for the 200 mg group (p < 0.05). In the 200 mg group there was a significant decrease, compared with placebo, in SBP at 1 min (p < 0.05) and at 2 min (p < 0.05) after intubation. In this study, adequate haemodynamic control following was obtained with the administration of 200 mg of esmolol.

Transfusion-related acute lung injury (TRALI) in an obstetric patient.

Transfusion-related lung injury (TRALI) is the leading cause of mortality following transfusion of blood products. Despite increasing awareness, the condition often remains unrecognised and therefore underreported. A 28-year-old with moderate preeclampsia had a post-partum haemorrhage following emergency caesarean section. Shortly after receiving three units of packed red cells she went into respiratory failure, which progressed to cardiac arrest. She was successfully resuscitated and made a slow but full recovery. Investigation through the National Blood Service confirmed the diagnosis of TRALI. TRALI is an increasingly common life-threatening complication of blood transfusion and should be included in the differential diagnosis of collapse in an obstetric patient who has recently received a blood product transfusion.

Use of red cells preserved in extended storage media for exchange transfusion in anti-k haemolytic disease of the newborn.

Anti-k is a Kell-related antibody. There is little correlation between the maternal antibody titre and the severity of haemolytic disease of the foetus and newborn, and anaemia is usually associated with low bilirubin levels. Severe erythroblastosis has been reported with a low titre anti-k (IAT 8-16). We report a case of severe haemolytic disease of the newborn (HDN) due to anti-k. HDN was associated with a normal bilirubin level and reticulocytopenia. The foetus was monitored by ultrasound, and delivery by elective caesarean section (CS) was planned. The mother was admitted 1 week before the expected date of delivery, and the infant was delivered by urgent CS. The infant required exchange transfusion. As suitable plasma-reduced (k antigen(-)) red cell units were not readily available, k- SAGM red cell units (preserved in extended storage media: SAGM sodium chloride, adenine, glucose and mannitol) were provided. The post-transfusion Hb remained stable, and the infant did not require further transfusion support. Our findings (reticulocytopenia and normal bilirubin levels) support the hypothesis that the pathogenesis of anaemia and haemolysis in anti-k HDN may be similar to that in anti-K (suppression of erythropoesis and immune destruction of K+ erythroid progenitor cells by macrophages in the foetal liver). The ideal product for exchange transfusion is plasma-reduced RBC, less than 5-days old. We provided a 4-day-old SAGM red cell unit for exchange transfusion in a term infant, and this was uneventful. Caution should be taken, however, and renal function and electrolyte levels should be monitored closely. More information is required regarding the safety of SAGM units for exchange transfusion.