The effect of an antimicrobial stewardship programme in two intensive care units of a teaching hospital: an interrupted time series analysis.

OBJECTIVES: To evaluate the effect of an antimicrobial stewardship programme in two intensive care units (ICUs) of a teaching hospital. METHODS: Between January 2017 and June 2018 we conducted a prospective, interventional, interrupted time-series study, based on Prospective Audit and Feedback in two ICUs of an acute-care teaching hospital. The primary outcomes were the difference in the antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug-resistant (MDR) organisms. The secondary outcomes included the hospital mortality rate, the mean length of stay and the antibiotic expense. RESULTS: During the study, 231 audits were performed, evaluating 693 antibiotic prescriptions. The programme led to a global reduction in antibiotic consumption, with a change in level (CL) of -324.8 defined daily doses (DDD)/100 patient-days (PD), p 0.04, and particularly in the use of fluoroquinolone: (CL: -63.48 DDD/100 PD, p < 0.001). A non-significant reduction was obtained for the consumption of carbapenems (CL: -34.7 DDD/100 PD, p 0.25) and third- and fourth-generation cephalosporins (CL: -27.3 DDD/100 PD, p 0.102). Furthermore, we registered a significant decrease in all BSI (CL: -5.8 events/100 PD, p 0.026) and in BSI due to MDR Gram-negative organisms (CL: -2.96 events/100 PD, p 0.043). No difference was observed in the hospital mortality and length of stay. CONCLUSIONS: Our study demonstrated that implementation of an antimicrobial stewardship programme in two ICUs of a teaching hospital induced a significant reduction in antibiotic consumption and in the incidence of BSI due to MDR Gram-negative organisms, without any impact on the mortality rate.

Eighteen-month lamivudine prophylaxis on preventing occult hepatitis B virus infection reactivation in patients with haematological malignancies receiving immunosuppression therapy.

This study evaluated the long-term efficacy and safety of an 18-month lamivudine prophylaxis in 68 HBsAg-negative/anti-HBc-positive patients with oncohaematological disease. All 68 consecutive HBsAg-negative/anti-HBc-positive patients with an oncohaematological disease and naïve for chemotherapy observed from April 2008 to December 2012 at 2 Hematology Units in Naples were treated with lamivudine for 18 months after stopping chemotherapy and monitored for HBsAg at months 1 and 3 during chemotherapy and then every 3 months after its discontinuation. During follow-up, 13 (19.1%) of the 68 patients died of complications related to their oncohaematological disease, and 3 (4%) showed a virological HBV reactivation (retroconversion to HBsAg positivity) 1-7 months after the discontinuation of lamivudine prophylaxis (2 treated for chronic lymphocytic leukaemia and one for Waldenstrom's disease); of these, 2 showed a biochemical reactivation. Comparing the demographic and clinical characteristics of the 3 patients with a virological HBV reactivation to the 65 without, the former were older (median age and range: 67 years [75-78] vs. 61 [24-88]; P = .05) and were less frequently treated for B-cell non-Hodgkin lymphoma (B-NHL) (0 vs. 70.7%, P = .03). In conclusion, a 18 months of lamivudine prophylaxis was effective in preventing HBV reactivation in HBsAg-negative/anti-HBc-positive patients treated for B-NHL. However, in patients with chronic and severe immunodepression, such as those with chronic lymphocytic leukaemia and Waldenstrom's disease, prophylaxis should be continued for an indefinite period.

[Evaluation of central venous catheters by endocavitary ECG]. / Registrazione elettrocardiografica intratoracica (EC-ECG) per valutare il catetere venoso centrale.

Jugular vein catheterization (JVC) is adopted for blood access in patients with acute renal failure, chronic renal failure and when patients demonstrate traditional vascular access (VA) failure. We believe that the best technique, first described by Serafini et al, to establish the position of a central venous catheter (CVC) is endocavitary electrocardiography (EC-ECG) and its use is recommended in all uremic patients requiring hemodialysis (HD). This technique uses the tip of the CVC as a reference point in standard electrocardiography. From 2001 to March 2004, we successfully applied this CVC technique in 33 patients requiring HD. The EC-ECG technique is a method that complies with the Food and Drug Administration guidelines regarding catheter tip location in uremic patients.

Relative roles of intestinal absorption and dialysis-fluid-related exposure in the accumulation of aluminium in haemodialysis patients.

BACKGROUND: A recent retrospective study has clearly demonstrated a reduction of cases with positive bone aluminium (Al) staining in the Italian dialysis population, which in general has had a low prevalence of bone Al toxicity. In the present study we tried to better address the relative role played, in our study population, by enteral and parenteral exposure to Al in reducing bone accumulation. METHODS: We retrospectively examined the data of 105 DFO tests and bone Al determinations performed in dialysis patients from 1984 to 1995. Enternal exposure was analysed by accurate anamnestic records, while parenteral exposure was evaluated by the determination of Al content in dialysis fluids. Bone Al content was assayed chemically and histochemically, while serum Al was assayed spectrophotometrically. Data pertinent to the patients were allotted into three period groups: 1984-1987; 1988-1991; 1992-1995. As for Al concentrations in dialysis fluids, the interval 1980-1983 (immediately before the start of our study), which could clearly have influenced bone Al content, was also considered. RESULTS: Basal serum Al showed some fluctuations (42.7 +/- 34.1; 24.8 +/- 21.9 and 38.9 +/- 34.9 micrograms/l respectively in the three groups, ANOVA P < 0.01) but only values of the period 1988-1991 were significantly lower than those of the period 1984-1987 (P < 0.05). Increments after DFO did not differ in the three periods (136.5 +/- 105.7; vs 98.7 +/- 91.7 and 106.1 +/- 96.2 micrograms/l respectively, P = n.s.). Enteral exposure to drugs containing Al was comparable (4.1 +/- 2.9 vs 4.0 +/- 4.6 and 5.8 +/- 7.9 total kg ingested respectively; P = n.s.), but bone Al was dramatically reduced (from 60.7 +/- 43.0 to 29.0 +/- 24.4 and 31.9 +/- 29.9 mg/kg/dw respectively; P < 0.0001), along with the definite disappearance of Aluminon-positive cases and Al-related bone disease (ARBD) after 1991. Parenteral exposure through the dialysate dropped from a mean of 26 +/- 14 micrograms/l in the 4-year period prior the start of the study (1980-1983) to 9 +/- 6 micrograms/l in the period 1984-1987 and to 4.9 +/- 2.1 micrograms/l and 5.0 +/- 2.0 micrograms/l respectively thereafter (P < 0.0001). CONCLUSIONS: Despite the persistence of oral exposure to Al, responsible for the observed stability of serum Al levels, a definite reduction of bone Al content has been recorded in our dialysis population, and ARBD has disappeared. This result has to be referred essentially to the optimal control of Al content in dialysis fluids, which is confirmed as a major factor for Al intoxication.

Procollagen type 1 C-terminal extension peptide serum levels following parathyroidectomy in hyperparathyroid patients.

Procollagen type 1 is mainly synthesized by osteoblasts and, after cleavage of the N- and C-terminal extension peptides, is utilized for collagen fibril deposition in the osteoid tissue. Serum levels of C-terminal extension peptide (Pcoll-1-C) of the procollagen molecule has been considered a useful marker for the evaluation of the rate of osteoblastic procollagen synthesis. To appraise whether in vivo parathyroid hormone (PTH) plays a suppressive role in the synthesis of procollagen type 1, a study has been carried out in 16 patients, 10 with severe secondary hyperparathyroidism of chronic renal failure and 6 with primary hyperparathyroidism. Following parathyroidectomy (PTX), in chronic renal failure patients a 94% fall in serum intact iPTH and a decline of serum calcium to hypocalcemic levels requiring calcitriol administration were observed. Serum Pcoll-1-C increased markedly with a peak after 7 days and a subsequent decline. Similar changes were observed for alkaline phosphatase and osteocalcin. In primary hyperparathyroidism, PTX was followed by an 88% drop in iPTH and mild hypocalcemia not requiring calcitriol administration. Also in this group serum Pcoll-1-C increased significantly with the same time course, unaccompanied by changes in alkaline phosphatase and osteocalcin. In 4 unsuccessfully neck-operated control patients no change in serum Pcoll-1-C levels was recorded during a period of 2 weeks postoperatively. In conclusion, acute withholding of parathyroid hypersecretion is accompanied by an abrupt and transitory increase of serum Pcoll-1-C, not dependent on calcitriol administration. Hypocalcemia following PTX may in part be due to uncoupling of bone formation and resorption.

Eight days of cyclosporine overdose: a case report.

A 25-year-old woman was admitted to the hospital because of rising trough cyclosporine concentrations thought to be due to self-administration of 4 times the normal dosage of the drug for 8 days. Her symptoms included colicky central abdominal pains and urinary retention; her serum creatinine concentrations were elevated. Whole blood cyclosporine and metabolite concentrations were measured by high-performance liquid chromatography and monoclonal radioimmunoassays. The highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17) concentration was 3425 ng/ml. A cyclosporine half-life of 91 hours was calculated. Nine days after the agent was discontinued the patient's serum creatinine concentration had returned to normal and her symptoms resolved. Due to the availability of three sizes of cyclosporine capsules, and the need for frequent dosage changes, continued vigilance is necessary to ensure that patients understand their drug regimen.

Kinetic factors and form determination of the head of bacteriophage T4.

The form of the bacteriophage T4 prehead is described by its icosahedral symmetry, its diameter, and its length. We show how each of these parameters is regulated during prehead formation and ascribe specific form-determining functions to the prehead proteins. The major protein of the head shell can assemble in several different forms. The structure produced in vivo depends on the rate of synthesis of the major protein relative to the rates of synthesis of minor shell proteins and the major core protein. From our observations, we propose a model for form determination of the prehead and suggest a pathway for the evolution of its prolate shape.

Isolation and characterization of bacteriophage T4 mutant preheads.

To determine the function of individual gene products in the assembly and maturation of the T4 prehead, we have isolated and characterized aberrant preheads produced by mutations in three of the T4 head genes. Mutants in gene 21, which codes for the T4 maturation proteases, produce rather stable preheads whose morphology and protein composition are consistent with a wild-type prehead blocked in the maturation cleavages. Mutants in gene 24 produce similar structures which are unstable because they have gaps at all of their icosahedral vertices except the membrane attachment site. In addition, greatly elongated "giant preheads" are produced, suggesting that in the absence of P24 at the vertices, the distal cap of the prehead is unstable, allowing abnormal elongation of broth the prehead core and its shell. Vertex completion by P24 is required to allow the maturation cleavages to occur, and 24- preheads can be matured to capsids in vitro by the addition of P24. Preheads produced by a temperature-sensitive mutant in gene 23 are deficient in core proteins. We show that the shell of these preheads has the expanded lattice characteristic of the mature capsid as well as the binding sites for the proteins hoc and soc, even though none of the maturation cleavage takes place. We also show that 21- preheads composed of wild-type P23 can be expanded in vitro without cleavage.

New method for localizing proteins in periodic structures: Fab fragment labeling combined with image processing of electron micrographs.

Fab fragments prepared from antisera directed against purified bacteriophage T4 structural proteins and head-related structures were used to label proteins on the surface of T-even giant phage capsids. Optically filtered electron micrographs of the Fab-labeled capsids reveal both the location of specific proteins within the capsomeres and differing conformational states of the protein subunits. We describe parameters affecting the utility of this technique for the study of molecular organization and protein conformation in periodic biological structures.

Localization of minor protein components of the head of bacteriophage T4.

The bacteriophage T4 capsid contains a number of minor proteins that are required for head assembly but whose detailed function and position in the head are unknown. We have found that by systematically varying the conditions of extraction, some of these minor proteins can be removed while the main capsid structure is left substantially intact. Electron microscopic examination of the residual capsids showed that the extraction of the product of gene 20 is correlated with the loss of a plug that distinguishes one vertex position (presumably the tail attachment site) from the others. Extraction of the product of gene 24 is correlated with the loss of the other 11 (nonproximal) vertexes of the capsid. We further show that antibody to P24 binds specifically to the nonproximal vertexes of both T4 preheads and T4 phages. On the basis of our findings, we suggest that P20 is located at or near the tail attachment site of the capsid, whereas P24 forms the 11 nonproximal vertexes of preheads and P24 forms the nonproximal vertexes of the mature head.