Pre-emptive Antibiotic Therapy Research Articles

Assessing the impact of positive cultures in preservation fluid on renal transplant outcomes: a scoping review.

Infection following kidney transplantation is a significant risk factor for adverse outcomes. While the donor may be a source of infection, microbiological assessment of the preservation fluid (PF) can mitigate potential recipient contamination and help curb unnecessary antibiotic use. This scoping review aimed to describe the available literature on the association between culture-positive preservation fluid, its clinically relevant outcomes, and management. Following the Joanna Briggs Institute's scoping review recommendations, a comprehensive search in databases (EMBASE, MEDLINE, and gray literature) was conducted, with data independently extracted by two researchers from selected studies. We analysed 24 articles involving 12,052 samples, predominantly published post-2000, 91%of whichretrospective. The prevalence of culture-positive preservation fluid varied from 0.86 to 77.8%. Coagulase-negative staphylococci emerged as the most frequently isolated pathogen in 14 studies. The presence of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), observed in two studies involving 1074 donors, was significantly associated with an increased risk of probable donor-derived infections (p-DDI). Of the reviewed articles, 14 reported on probable donor-derived infections, while 19 addressed the topic of preemptive antibiotic therapy. Routine culturing of preservation fluid is crucial for the identification of pathogenic organisms, facilitates targeted treatment and prevents probable donor-derived infections. Furthermore, this approach helps avoid the treatment of low-virulence contaminants, thereby reducing unnecessary antimicrobial use and the risk of antibiotic resistance. In cases where ESKAPE or Candida species are detected, preemptive therapy appears to be an important strategy. Given that the current evidence primarily stems from retrospective studies, there is a pressing need for large-scale, prospective trials to corroborate these recommendations. This scoping review currently represents the most thorough compilation of evidence on how contamination of preservation fluids affects kidney transplant management.

The Association of Organ Preservation Fluid Pathogens with Early Infection-Related Events after Kidney Transplantation.

(1) Background: The need to elucidate the microbial patterns in preservation fluid and explore their relationship with early infection-related events post kidney transplant and investigate antimicrobial resistance and the effects of preemptive antibiotic therapy. (2) Methods: This retrospective study analyzed the clinical data of 514 kidney transplant donors and 808 recipients from April 2015 to October 2020. Clinical data of donor and recipient characteristics, preservation fluid microbes, early infections (≤30 days), probable donor-derived infections (P-DDIs), antimicrobial resistance and preemptive antibiotic therapy was collected. (3) Results: The incidence of bloodstream (10.3% versus 5.2%, p = 0.006) and graft-site infections (9.7% versus 4.6%, p = 0.004) was significantly higher in recipients with culture-positive preservation fluid. In addition, recipients with ESKAPE pathogens or Candida species had a notably higher rate of bloodstream infections (14.1% versus 6.9%, p = 0.033) and graft-site infections (16.7% versus 3.5%, p < 0.01) than those with other positive pathogens. Preemptive antibiotic therapy decreased the bloodstream infection rate (11.8% versus 35.7%, p = 0.047) when preservation fluid was positive for ESKAPE pathogens. (4) Conclusions: Culture-positive preservation fluid has potential implications for kidney transplant recipients. ESKAPE pathogens or Candida species in preservation fluid as well as their antimicrobial resistance properties and non-preemptive antibiotic therapy could pose a risk of early infection-related events.

210. Outcomes of Kidney Transplant Recipients with Donor Positive Blood Cultures

Abstract Background Based on expert opinion, solid organ transplant recipients from donors with bacteremia are treated with 7-14 days of pre-emptive antibiotic therapy (PAT). However, studies addressing necessity, optimal duration of therapy, and outcomes in kidney transplant recipients (KTR) are lacking. Methods We retrospectively reviewed all kidney transplants performed at our institution from 01/01/2015-01/01/2021 to identify those cases where matched deceased donors had positive blood cultures. Bacteremia was defined per CDC criteria. We analyzed rate of infection in the KTR with the same organism identified in the donor blood culture within 30 days of transplantation. Results A total of 56 KTRs with donor positive blood cultures were identified. Demographic data are summarized in Table 1. Twenty of 56 cases (35.8%) had bacteremia and 36 (64.2%) had organisms classified as common commensals. The most common organisms in the bacteremia group were Gram-negative bacteria (12/20) and Staphylococcus aureus (6/20). Most common commensals were coagulase-negative staphylococci (26/36) (Table 2). All KTR received preoperative antibiotics at the time of transplantation, primarily cefazolin (15/20), and vast majority received TMP/SMX prophylaxis, for Pneumocystis jirovecii, post-transplant (19/20). PAT was administered in 70% (14/20) cases of bacteremia for a median of 8.5 days (IQR 7-14), while six cases were left untreated (Table 2). In contrast, majority of cases with common commensals were not treated (75%, 27/36). Of the cases treated (9/36), median duration of therapy was 7 days (IQR 5-14). No cases of infection with the same organism identified in the donor blood culture were reported in KTR within 30 days of transplantation. Conclusion KTR donors with bacteremia who were treated received a median of 8.5 days of PAT with no instances of breakthrough infection. In contrast, majority of donor blood cultures with organisms classified as common commensals were not treated and did well. Future studies are needed to assess whether perioperative antibiotics coupled with TMP/SMX prophylaxis post-transplantation are sufficient in select cases of transplantation from donors with bacteremia. Disclosures All Authors: No reported disclosures

Bilateral acute renal cortical necrosis after a dog bite: case report

BackgroundCapnocytophaga canimorsus is a Gram-negative capnophilic rod and part of dogs/cats’ normal oral flora. It can be transmitted by bites, scratches, or even by contact of saliva with injured skin. Asplenic patients and patients with alcohol abuse are at particular risk for fulminant C. canimorsus sepsis. However, also immunocompetent patients can have a severe or even fatal infection. This is the first case of a severe C. canimorsus infection in an immunocompromised host complicated by acute renal cortical necrosis with a “reverse rim sign” in contrast-enhanced computed tomography on hospital admission.Case presentationWe report the case of a 44-year functionally asplenic patient after an allogeneic stem cell transplantation, who presented with septic shock after a minor dog bite injury 4 days prior. Because of abdominal complaints, epigastric pain with local peritonism, and radiological gallbladder wall thickening, an abdominal focus was suspected after the initial work-up. The patient underwent emergent open cholecystectomy, but the clinical suspicion of abdominal infection was not confirmed. Septic shock was further complicated by cardiomyopathy and disseminated intravascular coagulation. As a causative pathogen, C. canimorsus could be isolated. The clinical course was complicated by permanent hemodialysis and extensive acral necrosis requiring amputation of several fingers and both thighs.ConclusionWe present a severe case of a C. canimorsus infection in a functionally asplenic patient after a minor dog bite. The clinical course was complicated by septic shock, disseminated intravascular coagulation, and the need for multiple amputations. In addition, the rare form of acute renal failure - bilateral acute renal cortical necrosis – was visible as “reverse rim sign” on computed tomography scan. This case is an example of the potential disastrous consequences when omitting pre-emptive antibiotic therapy in wounds inflicted by cats and dogs, particularly in asplenic patients.

Bacteriological pattern and their correlation with complications in culture positive cases of acute bacterial conjunctivitis in a tertiary care hospital of upper Assam: A cross sectional study.

Acute conjunctivitis is inflammation of conjunctiva of less than 3 to 4 weeks duration, characterized by cellular infiltration and exudation. It may also result into corneal, lid or orbital involvement which may lead to various complications.A hospital based prospective study was conducted in Assam Medical College and Hospital with 110 culture proven acute bacterial conjunctivitis cases. Primary objective was to evaluate the bacteriological pattern and secondary objectives were to evaluate seasonal variation, association of different organisms with various complications and antibiotic sensitivity pattern of the isolates.Maximum frequency of bacterial conjunctivitis observed from May to September. SA was the predominant organism isolated throughout the year (32.1%). Commonest single organism isolates were SE (26.1%) and SA (21.6%). True membrane formation was significantly associated with CD (P < .05), whereas pseudo-membrane formation was associated with SA and STBH isolation (P < .05). Isolation of SE, SA, and PA was associated with corneal involvement (P < .05). Lid involvement was seen with SA and Diphtheroid, whereas SP isolation was associated with concomitant dacryocystitis (P < .05). All the major organisms were (SE, SA, D, STBH, SP) highly sensitive to amino-glycosides, cephalosporins, chloromphenicol, vancomycin and linezolid, whereas high level of resistance was seen towards fluroquinolones (ciprofloxacin and moxifloxacin).All acute bacterial conjunctivitis cases don’t require antibiotic therapy. In case if required, periodical culture and sensitivity may guide initial pre-emptive antibiotic therapy. Further choice of antibiotic should be govern by culture and sensitivity status.

The impact of carbapenemase-producing Enterobacteriaceae colonization on infection risk after liver transplantation: a prospective observational cohort study

ObjectiveTo investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). MethodsProspective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. ResultsWe analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21). ConclusionsCPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

The Impact of Culturing the Organ Preservation Fluid on Solid Organ Transplantation: A Prospective Multicenter Cohort Study.

BackgroundWe analyzed the prevalence, etiology, and risk factors of culture-positive preservation fluid and their impact on the management of solid organ transplant recipients.MethodsFrom July 2015 to March 2017, 622 episodes of adult solid organ transplants at 7 university hospitals in Spain were prospectively included in the study.ResultsThe prevalence of culture-positive preservation fluid was 62.5% (389/622). Nevertheless, in only 25.2% (98/389) of the cases were the isolates considered “high risk” for pathogenicity. After applying a multivariate regression analysis, advanced donor age was the main associated factor for having culture-positive preservation fluid for high-risk microorganisms. Preemptive antibiotic therapy was given to 19.8% (77/389) of the cases. The incidence rate of preservation fluid–related infection was 1.3% (5 recipients); none of these patients had received preemptive therapy. Solid organ transplant (SOT) recipients with high-risk culture-positive preservation fluid receiving preemptive antibiotic therapy presented both a lower cumulative incidence of infection and a lower rate of acute rejection and graft loss compared with those who did not have high-risk culture-positive preservation fluid. After adjusting for age, sex, type of transplant, and prior graft rejection, preemptive antibiotic therapy remained a significant protective factor for 90-day infection.ConclusionsThe routine culture of preservation fluid may be considered a tool that provides information about the contamination of the transplanted organ. Preemptive therapy for SOT recipients with high-risk culture-positive preservation fluid may be useful to avoid preservation fluid–related infections and improve the outcomes of infection, graft loss, and graft rejection in transplant patients.

Pre-emptive antibiotic therapy to reduce ventilator-associated pneumonia: "thinking outside the box".

Mechanically ventilated, intubated patients are at increased risk for tracheal colonization with bacterial pathogens that may progress to heavy bacterial colonization, ventilator-associated tracheobronchitis (VAT), and/or ventilator-associated pneumonia (VAP). Previous studies report that 10 to 30 % of patients with VAT progress to VAP, resulting in increased morbidity and significant acute and chronic healthcare costs. Several natural history studies, randomized, controlled trials, and a meta-analysis have reported antibiotic treatment for VAT can reduce VAP, ventilator days, length of intensive care unit (ICU) stay, and patient morbidity and mortality. We discuss early diagnostic criteria, etiologic agents, and benefits of initiating, early, appropriate intravenous or aerosolized antibiotic(s) to treat VAT and reduce VAP, to improve patient outcomes by reducing lung damage, length of ICU stay, and healthcare costs.

Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications

Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.

Clinical and microbial impact of screening kidney allograft preservative solution for bacterial contamination with high-sensitivity methods

The clinical and bacteriological consequences of routinely performing highly sensitive bacterial screening of kidney transplant preservation solution (PS) are not known. To evaluate the clinical and microbiological impacts of this strategy, we retrospectively analyzed 200 consecutive kidney allograft recipients from March 2009 to February 2011 for whom PS samples were routinely screened. PS were inoculated into aerobic and anaerobic blood culture bottles, as well as blood agar plates. A rectal swab for extended-spectrum β-lactamase-producing Enterobacteriaceae (EBSL-PE) faecal carriage was also routinely obtained from each patient at admission and every 7 days until hospital discharge. In addition, a standard culture of drain fluid was collected on the day after kidney transplantation. Complete samples and cultures of PS were performed in 165 cases (82.5%), and 62 (37.6%) had positive blood culture results. The most frequent microbial agent isolated was coagulase-negative staphylococci (51.8%). Of these 62 positive samples, only seven (11.3%) were confirmed to contain the same organism by the standard culture method. Drain fluid and PS culture positivity with the same microorganism occurred in only two patients. Of the 62 patients with positive PS cultures, 26 (41.9%) received pre-emptive antibiotic therapy initiated within 48 h post-transplant. During the hospitalization period, patients with a positive PS culture, regardless of whether they received pre-emptive antibiotic therapy, did not exhibit any invasive infections (urinary, blood, peritoneal or wound) related to the microorganisms isolated in the PS. Patients with positive PS cultures who were treated with antibiotic therapy acquired significantly more colonizing ESBL-PE than patients who did not receive antibiotics (53.8% vs. 16.6%; P = 0.01); these patients also developed more clinical infections related to the ESBL-PE (23.1% vs. 5.2%; P < 0.01). The use of antibiotics for patients with positive PS cultures was an independent risk factor for ESBL-PE acquisition in both univariate and multivariate analyses. In conclusion, the use of more sensitive culture methods increases the rate of bacterial contamination of PS and is associated with an increased prescription of antibiotics and increased ESBL-PE carriage and related infections. Therefore, the systematic use of PS blood bottle cultures in kidney transplantation may have no benefit and might increase the rate of ESBL-PE emergence.

The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea

The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.

Cost-analysis of PCR-guided pre-emptive antibiotic treatment of Staphylococcus aureus infections: an analytic decision model

The aim of this study is to examine whether rapid polymerase chain reaction (PCR)-based screening is a cost-efficient tool to optimize pre-emptive antibiotic therapy of methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA, respectively) infections. A decision analytic cost model was developed, based on data from the peer-reviewed literature. Sensitivity analyses were undertaken to investigate the impact of variation in the MRSA rate, cost ratio of the cost of inappropriate antibiotic therapy to the cost of appropriate antibiotic therapy, PCR test cost, and total hospital costs per case. At a current MRSA rate of 24.5% in Germany, PCR-guided treatment regimens are cost-efficient compared to empirical strategies. The costs of alternative treatment strategies differ, on average, up to 1,780 <euro> per case. An empirical MRSA treatment strategy is least costly when the cost ratio is less than 1.06. When the total hospital cost per MRSA case is increased, pre-emptive MSSA treatment with PCR tests achieves the lowest average cost. Early verification and adaptation of an initial pre-emptive antibiotic treatment of S. aureus infections using PCR-based tests are advantageous in Germany and other European countries. PCR tests, accordingly, should be considered as elements in antimicrobial stewardship programs.

Administering intravenous immunoglobulin during infection is associated with infusion reactions in selected patients

Guidelines vary regarding the safety of administering intravenous immunoglobulin (IVIG) during infections, although evidence for this advice is lacking and is based on expert opinion. We retrospectively studied patients with common variable immunodeficiency who reacted during IVIG therapy as to whether routinely obtained markers of infection such as C-reactive protein (CRP) were elevated. 19 patients on replacement IVIG therapy in a hospital-based infusion unit were studied. CRP levels obtained were normalized to baseline levels without reactions (defined as 100). 8 of 19 patients had 16 reactions over a total of 107 infusions. Normalized CRP levels during reactions were higher [mean (±SD) of 258 (±215)] than during infusions with no reaction [mean 100 (±54.9), p = 0.017], and higher than in patients who did not react [mean 100 (±79.7), p = 0.017]. Some patients with IVIG reactions had elevated CRP levels suggesting that concurrent infection may have caused the reaction. Pre-emptive antibiotic therapy and delaying infusion could prevent unnecessary morbidity.

Factors affecting post-capture survivability of lobster Homarus americanus

Technological advances in gear and fishing practices have driven the global expansion of the American lobster live seafood market. These changes have had a positive effect on the lobster industry by increasing capture efficiency. However, it is unknown what effect these improved methods will have on the post-capture fitness and survival of lobsters. This project utilized a repeated measures design to compare the physiological changes that occur in lobsters over time as the result of differences in depth, hauling rate, and storage methodology. The results indicate that lobsters destined for long distance transport or temporary storage in pounds undergo physiological disturbance as part of the capture process. These changes are significant over time for total hemocyte counts, crustacean hyperglycemic hormone, L-lactate, ammonia, and glucose. Repeated measures multivariate analysis of variance (MANOVA) for glucose indicates a significant interaction between depth and storage methodology over time for non-survivors. A Gram-negative bacterium, Photobacterium indicum, was identified in pure culture from hemolymph samples of 100% of weak lobsters. Histopathology revealed the presence of Gram-negative bacteria throughout the tissues with evidence of antemortem edema and necrosis suggestive of septicemia. On the basis of these findings, we recommend to the lobster industry that if a reduction in depth and hauling rate is not economically feasible, fishermen should take particular care in handling lobsters and provide them with a recovery period in recirculating seawater prior to land transport. The ecological role of P. indicum is not fully defined at this time. However, it may be an emerging opportunistic pathogen of stressed lobsters. Judicious preemptive antibiotic therapy may be necessary to reduce mortality in susceptible lobsters destined for high-density holding facilities.

Systematic Microbiological Tests in Kidney Transplantation and Their Value in Predicting Posttransplantation Infection

Background Immunosuppressive therapy has many side effects among which is an increased infectious risk for the recipient. Transmission of pathogens from the graft to the recipient has not been well evaluated; there are no guidelines regarding the need for microbiological tests on the graft prior to transplantation. We routinely performed such tests to evaluate the risk and determine whether a patient should receive preemptive antibiotic therapy after transplantation. We herein have reported our preliminary results. Materials and Methods We reviewed 150 consecutive renal transplantations from cadaveric heart-beating donors. Microbiological tests were systematically performed not only on the preservation solution, but also on graft artery, vein, ureter, and perirenal fat. We reviewed the recipient's medical history for clinically significant infectious episodes in the first month after transplantation. Results Thirty-one percent of all microbiological tests were positive with 23 patients showing multiple positive tests, 74% of which were concordant. We documented 3 cases of direct graft-to-recipient pathogen transmission, all of which presented with 3 positive concordant tests. Graft culture prior to transplantation is often positive, but in more than half of the cases positive tests are either isolated or discordant. We only treated patients with concordant test results; no adverse consequence was observed among the untreated patients. Transmission occurred only in patients with at least 3 concordant tests. Conclusions Multiple microbiological tests on the graft prior to transplantation seemed useful to determine which patients would benefit from preemptive antibiotic therapy. Further studies may help to define which microbiological tests are the most important.

Streptococcus oralis endocarditis presenting as infective discitis in an edentulous patient

We present an interesting case of Streptococcus oralis endocarditis, presenting with infective discitis, in an edentulous patient with no underlying structural valvular heart disease and no clinical features to suggest infective endocarditis. It illustrates that S. oralis endocarditis can occur in edentulous patients (with no signs of oral sepsis), without any systemic stigmata of endocarditis and manifest with infection at remote sites, in this case, infective discitis. The diagnosis would also undoubtedly have been missed if preemptive antibiotic therapy had been given.

Preemptive Antibiotic Treatment Based on Gram Staining Reduced the Incidence of ARDS in Mechanically Ventilated Patients

Ventilator-associated pneumonia (VAP) is one of the major complications in the intensive care unit. VAP sometimes results in acute respiratory distress syndrome (ARDS), and the associated mortality is high. We hypothesized that preemptive antibiotic therapy based on results of bedside gram staining would reduce the incidence of VAP. Patients who were endotracheally intubated in our intensive care unit for more than 72 hours were included. Patients younger than 16 years of age or patients died because of brain death were excluded. The study was divided into two periods. During the first period, we used antibiotics according to the American Thoracic Society guidelines. During the second period, antibiotics were given according to the results of bedside gram staining even before radiographic infiltrate appeared. One hundred twenty-eight patients and 133 patients were included in the first and second periods, respectively. The incidence of VAP was significantly decreased in the second period (first period, 22%; second period, 9%, p < 0.01). The incidence of ARDS was also decreased significantly in the second period (first period, 11%; second period, 3%, p < 0.01). The duration and total amount of antibiotics administered did not increase in the second period. VAP associated mortality was significantly lower in the second period (first period, 5%; second period, 0.8%, p < 0.05). Early diagnosis and treatment of respiratory infection based on results of gram staining significantly reduced the incidences of VAP and ARDS without an increase in the use of antibiotics.

A randomized comparison of empiric or pre-emptive antibiotic therapy after hematopoietic stem cell transplantation

We performed a randomized comparison of pre-emptive and empiric antibiotic therapy for adult patients undergoing allogeneic or autologous stem cell transplantation. One hundred and fifty-three patients were randomized to receive cefepime either pre-emptively on the day that neutropenia (ANC<1.0 x 10(9) cells/l) developed irrespective of the presence of fever, or at onset of fever and neutropenia (empiric). Although there was no difference between the two arms in the proportion of patients developing fever or in the median number of days of fever, the time to onset of fever was a mean of 1 day longer in each patient on the pre-emptive arm (log rank P<0.001). The number of patients with bloodstream infections was significantly reduced in those receiving pre-emptive therapy (16/75) compared to the empiric arm (31/76) (P<0.01) but this did not translate into an appreciable clinical benefit as measured by days of hospitalization, time to engraftment, use of additional antimicrobial agents or mortality at 30 days. This study does not support the use of pre-emptive intravenous antibiotic therapy in adult stem cell transplant recipients.