Role Of Prophylaxis Research Articles

Cytomegalovirus infection in lung transplant patients: The role of prophylaxis and recipient-donor serotype matching

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in lung transplant recipients. We investigated the incidence of CMV infection in relation to CMV prophylaxis, and recipient-donor CMV serotype, in a cohort of 250 consecutive lung transplant recipients. All patients received 3 months CMV prophylaxis with acyclovir (n = 67) or gancyclovir (n = 183). Recipient-donor CMV serotype matching was performed in patients receiving acyclovir: R+/D+(n = 38), R+/D-(n = 10), R-/D+(n = 1), R- /D-(n = 16), unknown (n = 2). Recipient-donor CMV serotype matching was not performed in patients receiving gancyclovir: R+/D+(n = 71), R+/D-(n = 42), R-/D+(n = 38), R-/D-(n = 31), unknown (n = 1). The overall incidence of CMV infection was 51% (n = 34) in the acyclovir group, and 42% (n = 77) in the gancyclovir group (p = 0.14). During the first 9 months after transplantation, the rate of CMV infection was higher in the acyclovir group (42%) compared with the gancyclovir group (30%) (p = 0.005). Multivariate analysis demonstrated the incidence of CMV infection during the first 9 months was higher for acyclovir prophylaxis (p<0.001) and R-/D+ serostatus (p<0.001) and lower with R-/D- serostatus (p = 0.02). In conclusion, gancyclovir significantly delays the onset of first CMV infection among lung transplant patients. CMV surveillance and choice of prophylaxis may be modified according to donor-recipient CMV serotype.

The prevention of infection post-transplant: the role of prophylaxis, preemptive and empiric therapy

The close linkage of infection with the nature and intensity of the transplant immunosuppressive program has led to the concept of the therapeutic prescription. This has two components: an immunosuppressive one to prevent or treat rejection and graft-versus-host disease and an antimicrobial one to make it safe. This review provides a conceptual framework to approach the risk and risk periods for infection in solid organ and hematopoietic stem cell transplant recipients as well as an approach to antimicrobial use in this population.

Assessment of maternal cerebral blood flow in patients with preeclampsia

Systemic vasoconstriction in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the begining of eclamptic attack and 3) the application of anticonvulsive therapy. A prospective clinical study included 92 pregnant women, gestational age 28-36 weeks. They were divided into three groups: normotensive (n=30), mild preeclampsia (n=33), and severe preeclampsia (n=29). We investigated maternal cerebral circulation by assessing the MCA. We registrated: pulsatility index (Pi), resistance index (Ri), systolic/diastolic ratio (S/D), and the maximum systolic, end diastolic and medium velocity. Patients with severe preeclampsia were divided into two subgroups. subgroup 1 included patients without symptoms of threatening eclampsia (n=18; 62.06%); while subgroup 2 included those with symptoms of preeclampsia (n=11; 37.94%). All patients with severe preeclampsia were treated with magnesium sulfate (MgSO4), and cerebral blood flow was measured before and after the treatment. Statistical analysis was done by oneway ANOVA, Student t-test and t-paired sample test. The difference was considered to be significant if p<0.05. Significantly increased Pi, Ri and all velocities were established in the group of patients with severe preeclampsia compared with the other two groups. In the group with severe preeclamsia we registrated significantly increased values of all velocities (patients with signs of threatening eclampsia). After MgSO4 treatment in patients with severe preeclampsia significantly decreased values of Pi, Ri, S/D ratio and all velocities were registered. In the studied group of patients with severe preclampsia we found increased velocity values, Pi and Ri, especially in patients with signs of threatened eclampsia, suggesting that blood vessels changes are most prominent in severe preeclampsia. Cerebral blood flow meassurements can be used as a clinical test for the prediction of eclampsia. Magnesium-sulfate (MgSO4) has a signifficant role in prophylaxis and treatment of eclampsia, and, therefore, positive influence on reduction of cerebral ishemic lesions can be expected. We can conclude that changes of the cerebral blood flow can be evaluated by evaluating blood flow velocities in the medial cerebral artery. Velocities tend to increase in severe preeclampsia, especially with signs of threatening eclampsia, and decrease after treatment with mgnesium sulfate. Serial measurements of blood flow in medial cerebral artery in patients with severe preeclampsia may be used in prediction of eclampsia and in evaluation of magnesium sulfate therapy effects.

Prevention of Venous Thromboembolism in Surgical Patients

Venous thromboembolism (VTE) is a common complication of surgical procedures. The risk for VTE in surgical patients is determined by the combination of individual predisposing factors and the specific type of surgery. Prophylaxis with mechanical and pharmacological methods has been shown to be effective and safe in most types of surgery and should be routinely implemented. For patients undergoing general, gynecologic, vascular, and major urologic surgery, low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) are the options of choice. For low-risk urologic surgery, early postoperative mobilization of patients is the only intervention warranted. For higher-risk patients, including those undergoing elective hip or knee replacement and surgery for hip fracture, vitamin K antagonists, LMWH, or fondaparinux are recommended. For patients undergoing neurosurgery, graduated elastic stockings are effective and safe and may be combined with LMWH to further reduce the risk of VTE. The role of prophylaxis is less defined in patients undergoing elective spine surgery, as well as laparoscopic and arthroscopic surgery. A number of issues related to prophylaxis of VTE after surgery deserve further clarification, including the role of screening for asymptomatic deep vein thrombosis, the best timing for initiation of pharmacological prophylaxis, and the optimal duration of prophylaxis in high-risk patients.

Is there a role for prophylaxis against atrial fibrillation for patients undergoing lung surgery?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed whether prophylactic anti-arrhythmic drugs may prevent atrial fibrillation (AF) following lung resection. Altogether 457 papers were found using the reported search, of which 14 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. We identified single randomized trials that have demonstrated a benefit for Diltiazem, Bupivacaine epidural and magnesium for prophylaxis against AF in patients undergoing non-cardiac thoracic surgery, with a number needed to treat of between 4 and 8 with these regimes.

Primary CNS lymphoma: is there a role for prophylaxis against lymphomatous meningitis?

This part of the program extends the previous discussion of metastatic CNS disease to prophylaxis of primary CNS lymphoma against meningeal involvement.

Hepatic failure at obstructive parasitogenic cholestasis

In Tomsk zonal hepatologic center 358 patients with obstructive parasitogenic jaundice have been operated (alveococcosis-based — 43, echinococcosis-based — 17, opisthorchosis-based — 298). Clinical presentations of hepatic failure before the surgery have been observed at 30,7% of patients, more often — under long and intensive cholestasis. Postsurgical hepatic failure has developed at 23,1%. Intraportal medicine infusions play an important role in prophylaxis and treatment of hepatic failure along with timely and optimal surgery. Infusions permit to decrease the hepatic failure progress probability from 60,6 to 30,5%, probability of suppurative complications from 10,3 to 3,1% and postsurgical lethality from 38,2 to 9,5%.

Prevention of invasive fungal infections in liver transplant recipients: the role of prophylaxis with lipid formulations of amphotericin B in high-risk patients.

Invasive fungal infections (IFI) are associated with high mortality in liver transplant recipients. Prevention remains an elusive goal, especially for IFI caused by moulds. From January 1998, patients who fulfilled four or more variables identified as risk factors for IFI received a cumulative dose of 1-1.5 g of lipid formulations of amphotericin B (L-AmpB; AmBisome or Abelcet). The development of IFI in these patients was compared with historical patients. Two hundred and eighty liver transplant recipients were analysed over a period of 8 years. In the historical group, IFI were observed in 22 of 131 patients (17%) and invasive aspergillosis in 13 of them (10%). After January 1998, IFI were observed in nine of 149 (6%) (P < 0.01) and invasive aspergillosis in six patients (4%) (P = 0.08). In patients with four or more risk factors (high risk) for IFI, the administration of L-AmpB reduced the risk from 36% to 14% (P = 0.07), and the risk of aspergillosis from 23% to 5% (P = 0.08). Notably, prophylaxis reduced the risk of aspergillosis from 32% to 0% in dialysed patients (P = 0.03). Variables independently associated with IFI in high-risk patients were dialysis [odds ratio (OR) 3.9; 95% confidence interval (CI) 1-16.7] and surgical reintervention (OR 5.4; 95% CI 1.2-24.6), while L-AmpB was a protective factor in this multivariate analysis (OR 0.1; 95% CI 0.02-0.8). The analysis in these high-risk patients was not able to demonstrate an association between the administration of L-AmpB and higher survival. Selected risk factors are good predictors of IFI in liver transplant recipients. The administration of L-AmpB in high-risk patients is independently associated with a reduction of IFI.

Respiratory virus infections in the immunocompromised host.

The number of immunocompromised children in the population is increasing for a variety of reasons. Common respiratory viruses acquired in the community or in the hospital setting include the ortho- and paramyxoviruses and may cause severe lower respiratory tract disease in these children. Measles is again becoming a threat. Particularly in transplant patients, Herpes group viruses and adenoviruses, often part of a reactivation illness, can cause potentially life-threatening disease. The use of rapid molecular diagnostic techniques and an increasing array of antiviral therapies can help ensure a good outcome in many cases, although controlled clinical trial data are often lacking. Immunotherapeutic strategies using specific antibodies or cytotoxic T cells are being developed and are likely to have an increasing role in prophylaxis and pre-emptive therapy in the future. The development and introduction of vaccines against common respiratory diseases will help reduce the risks faced by these susceptible children.

Antibiotic prophylaxis in severe acute pancreatitis: Randomized multicenter prospective study with meropenem

Nowadays, most deaths in acute pancreatitis are caused by infection, thus the role of prophylaxis of infectious complications in, severe acute pancreatitis (SAP) still remains a debatable issue. Aim: The aim of the study was to assess the efficacy of prophylactic antibiotic treatment comparing rates of local and infectious complications, mean hospital stay, necessity of surgical treatment and mortality in two groups of patients with SAP Methods: Fourty one patients with SAP were enrolled into the randomized muhicenter prospective study according to the clinical criteria defined at the Atlanta symposium or CRP level exceeding 190 rag/1. The patients were randomized either into the prophylactic (P) or into the therapeutic (T) groap In the P-group, meropenem 500 nag was administrated every 8 hours for 10 days. In the T-group, the patients received the same antibiotic treatment only in the case of confirmed infectious complications (infected necrosis, abscess, urinary infection, pneumonia, catheter related bacteriemia etc.). Results are summarized in the table. Conclusions: Prophy~ hctic antibiotic treatment reduces the rate of infectious complications in patients with SAP. Although it does not decrease overall mortality, antibiotic prophylaxis can be recommended in patients with SAP.

A five-year clinical audit in the haematology ward of a tertiary care hospital: establishing degree of correlation between bacteraemia and oro-pharyngeal screens in immunocompromised patients and role of prophylaxis

A five-year clinical audit in the haematology ward of a tertiary care hospital: establishing degree of correlation between bacteraemia and oro-pharyngeal screens in immunocompromised patients and role of prophylaxis

Intravenous immunoglobulin: Appropriate indications and uses in hematopoietic stem cell transplantation

Intravenous immune globulin (IVIG) therapy has been prescribed in many different disease states. Hyperimmune products are also available. Recently, routine use for many indications has come under scrutiny secondary to high cost, limited supply, and unclear benefit. IVIG is U.S. Food and Drug Administration-approved for application in hematopoietic stem cell transplantation (HSCT), a very common indication for its use. In an attempt to clarify the most appropriate indications and doses in HSCT recipients, we conducted a MEDLINE search in which we reviewed all relevant articles from 1966 to the present. Search terms included bone marrow transplantation, intravenous immune globulin, hyperimmune globulin, GVHD, and cytomegalovirus (CMV). Also, the references of all pertinent studies and review articles were scanned for studies missed via MEDLINE. CMV prophylaxis/treatment and GVHD prophylaxis are the 2 indications with the most significant clinical support, but there are very few prospective, randomized, controlled trials reported. Furthermore, sample size usually was small, included heterogeneous patient populations, and employed different primary end points. Several reports support IVIG therapy in combination with ganciclovir for prevention and treatment of CMV infection, whereas others have shown ganciclovir monotherapy to be effective, blurring the benefit of IVIG administration. CMV IgG data are also imprecise and difficult to interpret. The role of IVIG therapy in prevention and treatment of GVHD also is vague. Only 1 randomized investigation showed a benefit in the prevention of acute GVHD, and no studies showed efficacy in chronic GVHD prophylaxis and therapy. Reports examining the utility of IVIG or CMV IgG in HSCT are hampered by marked variation in trial design and dosing and diverse patient characteristics. Although IVIG may be useful as a component of preemptive therapy and treatment of CMV disease, its contribution to the prevention of reactivation of CMV infection is dubious. Extended IVIG therapy during GVHD prevention may impair recovery of humoral immunity, and its role in prophylaxis and therapy of GVHD has not been clearly defined. Hospital monitoring programs may be a valuable way to detect areas of high use and allow for streamlining of prescribing.

The effect of Relenza treatment on the early immune response induced after influenza vaccination

Background: Although the new anti-influenza drugs are licensed for therapeutic use, it is anticipated that they will also play a role in prophylaxis in combination with vaccine. It is thus imperative to know the minimal time necessary for antiviral prophylaxis before a vaccine-induced protective immune response can be anticipated. Methods: We have conducted a double blind placebo controlled trial with 40 young healthy volunteers (18 males, 22 females; age range 21–32 years old) who were vaccinated intramuscularly with licensed split virus vaccine and received 20-mg Relenza (24 subjects) or placebo (16 subjects) daily for a period of 14 days. Heparinised blood was collected prevaccination and up to 42 days postvaccination and analysed using the ELISPOT and HI assays. Results: No significant differences were observed in the magnitude or time course of the antibody response between the Relenza and placebo groups for the influenza A/H3N2 and B strains. However, the placebo group responded better to the A/H1N1 strain than the Relenza group at 7 and 9 days postvaccination. Conclusions: Relenza treatment was necessary for a minimum of 1 week and by day 12 the majority of volunteers (>80%) had a protective HI titre to all three strains.

The effect of zanamivir treatment on the early immune response to influenza vaccination

Zanamivir is licensed for influenza treatment, but may also play a role in prophylaxis either alone or in combination with vaccine in epidemic periods. We conducted a double blind placebo controlled trial to investigate the effect of zanamivir treatment on the humoral immune response to influenza vaccine. Forty young healthy volunteers were vaccinated with licensed trivalent influenza vaccine and received 20 mg zanamivir (24 subjects) or placebo (16 subjects) daily for a period of 14 days. No significant differences were observed in the magnitude or the time course of the antibody response to the influenza H3N2 and B strains between the two groups, in contrast the placebo group responded with higher antibody titres to the H1N1. Our results suggest that during an influenza epidemic, volunteers would only need to continue zanamivir treatment for the initial 12 days after vaccination whilst the vaccine induced protective antibody response developed.

New strategies in the prevention of restenosis.

Restenosis is a common and serious complication following angioplasty and stent implantation in patients with arterial vascular disease. Restenosis is a form of intimal hyperplasia. Endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) stimulate intimal hyperplasia and may play a role in restenosis. ET-1 and VEGF may act in concert in promoting restenosis following mechanical injury to the vessel wall in angioplasty and stent implantation. An understanding of their mechanism of action may lead to more effective methods for preventing restenosis. ET-1 receptor antagonists may play a prominent role in prophylaxis.

Excision and Radiotherapy for Heterotopic Ossification of the Elbow

Radiotherapy has a well-defined role in prophylaxis of recurrent heterotopic ossification of the hip, but has been described infrequently in other situations. This article reports the use of excision and low-dose external beam radiotherapy in three patients with heterotopic ossification of the elbow treated between February 1995 and September 1996. Radiotherapy was delivered in a single fraction of 7-8 Gy within 48 hours postoperatively using opposed anteroposterior portals. After a median follow-up of 10.5 months, all three patients demonstrated a significant increase in range of motion without any evidence of recurrence. These results indicate adjuvant postexcision radiotherapy may be used for prophylaxis of recurrent heterotopic ossification of the elbow.

Renal hemodynamics in radiocontrast medium-induced renal dysfunction: A role for dopamine-1 receptors

Radiocontrast medium (RCM) administration induces a transient increase in renal blood flow (RBF), followed by a prolonged vasoconstriction. This vasoconstrictor phase in RBF is accompanied by a decrement in glomerular filtration rate (GFR). Nonselective dopamine (DA) receptor stimulation is known to increase RBF and GFR. Clinical studies, however, fail to demonstrate a renoprotective effect of DA following RCM administration. This lack of renoprotection may relate to nonspecific adrenergic stimulation by DA. The effect of select DA-1 receptor stimulation on renal hemodynamics following RCM administration has not been evaluated. This study tests the hypothesis that selective DA-1 receptor stimulation blunts the declines in RBF and GFR that follow RCM injections, independent of changes in baseline RBF and GFR. Experiments were performed in six anesthetized, volume-depleted dogs. RBF was measured by an electromagnetic flow probe around the renal artery and GFR by inulin clearance. After a 60-minute equilibration period, baseline values of RBF, GFR, and arterial pressure were determined. Two separate intrarenal bolus injections of the ionic RCM Renograffin were then given in the presence of saline infusion. After a 60-minute recovery period, intra-arterial infusions of either the selective DA-1 receptor agonist fenoldopam or the selective DA-1 receptor antagonist Schering 23390 were started in random order, and experiments were repeated. Neither agent significantly altered baseline values of arterial pressure, RBF, or GFR rate. Fenoldopam prevented reductions in GFR (-17 +/- 2 Deltaml/min, control vs. 2 +/- 1 Deltaml/min, fenoldopam, P < 0.001). Conversely, GFR was further reduced in the presence of Schering 23390 (-15 +/- 2 Deltaml/min, control vs. -23 +/- 1 Deltaml/min, Schering 23390, P < 0.05). Similarly, the maximal reduction in RBF was blunted with fenoldopam (-71 +/- 12 Deltaml/min, control vs. -3 +/- 2 Deltaml/min, fenoldopam, P < 0. 01), whereas Schering 23390 potentiated maximal RBF reductions following the RCM injection (-85 +/- 11 Deltaml/min, control vs. -119 +/- 14 Deltaml/min, Schering 23390, P < 0.05). The duration of recovery from vasoconstriction was also prolonged in the presence of Schering 23390 (342 +/- 35 seconds, control vs. 762 +/- 56 seconds, Schering 23390, P < 0.0001). We conclude that selective DA-1 receptor stimulation protects against RCM-mediated decrements in renal hemodynamics, independent of changes in baseline GFR and RBF. Clinical trials are required to examine whether selective DA-1 receptor stimulation may have a role in prophylaxis against nephropathy development in high-risk patients undergoing procedures that require RCM.

Update on postdural puncture headache

Postdural puncture headache (PDPH) is among the most common serious morbidities associated with spinal anesthesia, with an extrapolated incidence of <-3%. Risk factors include younger age, pregnancy, and the use of large diameter, cutting tip spinal needles. PDPH can be reduced by avoiding spinal anesthesia in patients less than 20 years old, and by using 25-or 27-gauge spinal needles with non-cutting tips. Early ambulation does not appear to increase the risk of PDPH. The theorized pathophysiology of PDPH is bimodal—attributed to 1) low cerebrospinal fluid volume and pressure secondary to transdural leak through a needle-induced dural defect, and 2) reactive vasodilation in response to stretching intracranial anchoring structures. Indirect anatomic and physiologic evidence supports these mechanisms. Epidural saline and caffeine therapies, though initially effective, have a limited treatment role because of high recurrence rates. Epidural blood patch is the treatment of choice, although its role in prophylaxis remains controversial.

Prophylaxis against hepatitis B recurrence following liver transplantation using combination lamivudine and hepatitis B immune globulin.

Patients undergoing liver transplantation for hepatitis B-related liver disease are prone to recurrence. The mainstay of prophylaxis has been passive immunotherapy with hepatitis B immune globulin (HBIG). Antiviral therapy with lamivudine has proven effective in lowering hepatitis B virus (HBV) DNA and improving histology in patients with hepatitis B infection; its role in prophylaxis against hepatitis B recurrence following liver transplantation is under investigation. Viral breakthrough and resistance, however, are a significant problem with monotherapy with either HBIG or lamivudine. The efficacy of combination lamivudine/HBIG prophylaxis has not been reported. Fourteen patients underwent transplantation for decompensated liver disease owing to hepatitis B. Lamivudine (150 mg p.o./d) was begun before transplantation in 10 patients, including 4 who were HBV DNA-positive. In addition, 1 patient was HBV DNA-positive when transplanted. HBIG was given perioperatively and continued thereafter; treatment with lamivudine was maintained or initiated at the time of transplantation and continued indefinitely. The median follow-up was 387 days. Actuarial 1-year patient and graft survival was 93% (1 patient died of unrelated causes). At a median interval of 28 days following lamivudine treatment, all 5 HBV DNA-positive patients cleared HBV DNA from the serum; 1 went on to clear hepatitis B surface antigen (HBsAg), before transplantation, at day 148 of lamivudine treatment. By the highly sensitive polymerase chain reaction (PCR), at a median of 346 days (range, 130-525 days) following transplantation, all 13 surviving patients had no detectable serum HBV DNA. Lamivudine suppresses HBV replication in patients awaiting liver transplantation. At a median follow-up of 1.1 years, combination prophylaxis with lamivudine and HBIG prevented hepatitis B recurrence following liver transplantation.

Covalent polymyxin B conjugate with human immunoglobulin G as an antiendotoxin reagent.

Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 microg of bound functional PMB per 100 microg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae relative to unconjugated IgG with MBCs of <4 microg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.