The Transplantation Society published guidelines on cytomegalovirus (CMV) management after solid organ transplantation in 2010, which provide recommendations on prevention, treatment, diagnostics, ...and resistance. We aimed to survey international clinicians on their posttransplantation CMV management practices with reference to these guidelines to see if they altered the management of clinicians caring for transplant patients.
The members of The Transplantation Society were emailed an electronic survey 12 months after the guideline publication.
A total of 155 clinicians responded, representing 126 centers in 41 countries. Overall, there was a high uptake of usage of the guidelines. High rates of initial CMV prevention were used (93%), with 46% using only universal prophylaxis, 21% only preemptive therapy, and 33% a hybrid combination dependent on recipient risk for CMV. Socioeconomic and geographic influence was evident, with 26% of respondents from developing countries using no CMV prevention, and more preemptive therapy used in Asia. Valganciclovir was the most common antiviral used, with dosing often below recommendations (33% in infection). Molecular monitoring was used by 84% of clinicians. Management of antiviral-associated neutropenia commonly included antiviral dose reduction or withdrawal (51%).
We conclude that there is significant geographic variation in CMV management after solid organ transplantation. Although the majority of clinicians adhere to consensus guidelines, opportunity exists to encourage better guideline uptake.
Rapid identification of microorganisms in blood cultures is required to optimize empirical treatment at an early stage. Fluorescence in situ hybridization (FISH) can reduce the time to identification ...of microorganisms in growth-positive blood cultures. In this study, we evaluated the performance, time to identification, and potential clinical benefits of FISH compared to those of conventional culture methods in routine practice. After Gram staining, blood culture fluids were simultaneously further identified with FISH and with conventional culture methods. Results and points in time of FISH and culture identification (provisional and final identifications) were collected and compared. For 91% of microorganisms, the genus or family name was identified, and for 79%, the species name could be attributed. The sensitivity and specificity of the individual probes exceeded 95%, except for the Enterobacteriaceae probe (sensitivity, 89%). Cross-hybridization was obtained with the Klebsiella pneumoniae probe for Klebsiella oxytoca. The time gains of FISH and final culture identification were more than 18 h for bacteria and 42 h for yeasts. With FISH, Staphylococcus aureus was differentiated from coagulase-negative staphylococci 1.4 h faster than by provisional identification (P < 0.001). In conclusion, FISH allows rapid and reliable identification of the majority of microorganisms in growth-positive blood cultures. The substantial time gain of identification with FISH may allow same-day adjustment of antimicrobial therapy, and FISH is especially useful if no provisional identification is obtained. With further extension of the number of probes and a reduction in turnaround time, FISH will become a very useful diagnostic tool in the diagnosis of bloodstream infections.
Transmitted resistant HIV may revert to wild-type in the absence of drug pressure due to reduced replication capacity (RC). We observed eight therapy-naive patients infected with HIV harbouring four ...mutations at nucleoside reverse transcriptase inhibitor (NRTI) resistance-related positions: M41L, T69S, L210E and T215S. If partial reverted resistance patterns like these are detected at baseline, concerns for more extensive resistance in the quasispecies often directs selection of first-line combination antiretroviral therapy (cART) towards more complex regimens.
Genotypic resistance testing and phylogenetic analysis was performed using pol sequences of 400 therapy-naive patients and 1322 patients with at least one NRTI-related mutation. Reverse transcriptase (RT) genes were cloned into a reference strain and RC was investigated.
Phylogenetic analysis showed that all eight patients are part of a transmission cluster (bootstrap value 92%). The patients resided in three distinct geographical regions and were either homosexually or heterosexually infected. Prior negative serology and analysis of base ambiguity demonstrated circulation for at least 7 years. In vivo evolution showed a mixture with wild-type (T215S/T) in only one untreated patient more than 6 years after diagnosis. The reverted resistance pattern did not confer a substantial reduction in RC compared with wild-type, explaining its persistence in vivo and long-term circulation in the population. Four patients started cART; three of them received quadruple cART. All patients showed good virological and immunological response.
Long-term circulation transcending distinct regions and transmission groups suggests reversion occurred in previous hosts in the transmission chain. Identification of clusters using epidemiological data and active-partner tracing may broaden therapeutic options in cases of transmitted resistance.
Abstract Background The significance of isolation of herpes simplex virus (HSV) type 1 from the lower respiratory tract in critically ill patients on mechanical ventilation is still unclear. In the ...current study, we used polymerase chain reaction techniques to quantify HSV-1 to further evaluate its role. Objectives The hypothesis was that high loads reflect invasive pulmonary disease related to prolonged mechanical ventilation and increased mortality, as opposed to shedding from the upper respiratory tract, which leads to lower viral loads. Study design We prospectively studied 77 consecutive patients admitted to the intensive care unit and analyzed 136 tracheal aspirates or bronchoalveolar lavage fluids, taken when clinically indicated in the diagnostic workup of fever, radiologic pulmonary infiltrates, progressive respiratory insufficiency or combinations. Samples were cultured for bacteria and yeasts according to routine microbiological methods and HSV-1 loads were determined by real time quantitative PCR. Viral loads were expressed per number of cells recovered. Results HSV-1 load was directly related to the simplified acute physiology score II ( rs = 0.47, P = 0.04) when the first specimen taken proved positive for HSV-1. HSV-1 positivity concurred with Candida spp. colonization. Patients with and without a HSV-1 load did not differ with respect to pulmonary and systemic courses and vital outcomes. Conclusions The data suggest that HSV-1 in the lower respiratory tract originates from shedding in the upper respiratory tract in about 30% of critically ill patients, following immune suppression and reactivation, without invasively infecting the lung. No attributable mortality was observed.
We evaluated a modified fluorescence in situ hybridization (FISH) assay for rapid (<1 h) identification of microorganisms in growth-positive blood cultures. The results were compared to those of the ...standard FISH technique and conventional culturing. The rapid identification of microorganisms with modified FISH can have important effects on clinical management of patients with bloodstream infections.
Background: The clinical significance and pulmonary pathogenicity of herpes simplex virus type 1 (HSV-1) in mechanically ventilated, critically ill patients are unclear.
Objective: To determine the ...clinical features and course of respiratory HSV-1 infections/colonisations in the critically ill, in order to evaluate the contribution to outcome.
Design: A retrospective cohort study in the intensive care unit of an university hospital, involving 22 patients with a HSV-1 isolated from bronchoalveolar lavage (BAL) fluid, divided into survivors (
n=13) and non-survivors (
n=9). All patients except for one survivor had been intubated and were mechanically ventilated.
Results: Non-survivors had acquired HSV-1 sooner on mechanical ventilation than survivors. Prior chronic heart disease was more prevalent in non-survivors than in survivors and, at the time of HSV-1 isolation, the mean creatinine level was higher (
P<0.05) in the former. Survivors had a somewhat greater fall in body temperature after a 10-day course of antiviral therapy than non-survivors, but the lung radiographic abnormalities prior to and after the course did not differ. There were no major differences in cardiorespiratory variables between outcome groups and causes of death and were judged not to relate, in general, to HSV-1.
Conclusions: Critically ill patients in whom HSV-1 from BAL is isolated, have about 40% chance of dying, mainly because of severe underlying disease and comorbidity, which may predispose to endogenous reactivation of the virus. There is no clinical evidence for direct cardiorespiratory pathogenicity and beneficial effects of antiviral therapy. HSV-1 isolated from lung secretions may thus be a marker rather than a mediator of severe illness.
The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear.
In four critically ill patients with persistent pulmonary infiltrates of ...unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(-3)/min) was measured.
The PLI ranged between 7.5 and 14.0 x 10(-3)/min in the study patients. Two patients received a course of acyclovir and all survived.
The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs.
Cefpirome, a fourth generation cephalosporin, was administered during 154 episodes of febrile neutropenia in 106 patients. We assessed the clinical efficacy of cefpirome and its activity against ...isolated pathogens in neutropenic patients with hematologic malignancies. In addition, the pharmacokinetics and optimal dosing regimen of cefpirome during neutropenia were investigated.
The most common complication of continuous subcutaneous insulin infusion (CSII) is inflammation at the infusion site. To determine possible risk factors to these infections, we studied several ...factors in the management of CSII and compared the pyogenic skin inflammation rate, the carriage rate of Staphylococcus aureus, and the HbA1 level among 50 CSII-treated diabetic patients, 50 diabetic patients on insulin injections, 48 diabetic patients on oral medication, and 40 healthy volunteers. There was no increased carriage rate of S. aureus among CSII-treated patients (42%) as compared with the other groups. An unexpected inverse relationship existed between HbA1 level and carriage rate in the CSII-treated group (HbA1 5-8%, n = 16, 69%; HbA1 8-10% n = 15, 40%; HbA1 greater than 10, n = 19, 21% P = .02). Pyogenic skin inflammations were reported by 24 (48%) CSII-treated patients, of which 18 had infected infusion sites, 6 (12%) insulin injecting patients, 2 (4%) patients on oral medication, and 3 (8%) healthy volunteers (P less than .01). The occurrence of inflamed infusion sites was not associated with carriage of S. aureus, the indwelling time of the needle, or the insulin dosage per day. There was an association, however, with the type of insulin preparation classified according to the added preservative: m-cresol-containing insulin (n = 24, 54%); methyl p-hydroxybenzoate-containing insulin (n = 26, 19%, P = .02). We concluded that the carriage of S. aureus is not increased among diabetic patients on CSII treatment and is not a risk factor in the occurrence of inflammation at the infusion site.
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