Initial Empirical Antimicrobial Therapy Research Articles

Febrile Neutropenic Infection Occurred in Cancer Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation

ObjectiveThe objective of this study was to investigate the incidence, risk factors, and clinical and prognostic characteristics of febrile infection that occurred during the neutropenic period in cancer patients who underwent autologous peripheral blood stem cell transplantation (APBSCT). MethodsClinical data of all the APBSCT cases from 2007 to 2009 in Sun Yat-sen University Cancer Center were collected and retrospectively analyzed. ResultsEighty-nine APBSCT subjects were investigated. Neutropenia usually occurred on the 4th day (range, 0–15) after transplantation and lasted 6 (range, 3–27) days. Febrile neutropenia occurred in 78.7% patients and lasted around 3 (range, 1–20) days and no infection-related deaths were observed. For febrile episodes, 12 patients (17.1%) were diagnosed as having microbiologically documented infections (MDI). Initial empirical antimicrobial therapy was given to all cases of post-APBSCT febrile neutropenia, of which 44 cases (62.9%) were effective. Febrile neutropenia occurred in 25/34 (73.5%) patients who were given antifungal drugs for prophylaxis. ConclusionsNeutropenic infection is still the major complication in APBSCT patients and duration of neutropenia is one of the major risk factors. Prophylactic administration of antifungal drugs seems to be invalid to reduce post-APBSCT infection. Sufficient doses of broad-spectrum antibiotics at the early stage lead to better results of initial antimicrobial treatment.

Accuracy of tracheal aspirate gram stain in predicting Staphylococcus aureus infection in ventilator-associated pneumonia

BackgroundThe Gram stain can be used to direct initial empiric antimicrobial therapy when complete culture is not available. This rapid test could prevent the initiation of inappropriate therapy and adverse outcomes. However, several studies have attempted to determine the value of the Gram stain in the diagnosis and therapy of bacterial infection in different populations of patients with ventilator-associated pneumonia (VAP) with conflicting results. The objective of this study is to evaluate the accuracy of the Gram stain in predicting the existence of Staphylococcus aureus infections from cultures of patients suspected of having VAP.MethodsThis prospective single-center open cohort study enrolled 399 patients from December 2005 to December 2010. Patients suspected of having VAP by ATS IDSA criteria were included. Respiratory secretion samples were collected by tracheal aspirate (TA) for standard bacterioscopic analysis by Gram stain and culture.ResultsRespiratory secretion samples collected by tracheal aspirates of 392 patients were analyzed by Gram stain and culture. When Gram-positive cocci were arranged in clusters, the sensitivity was 68.4%, specificity 97.8%, positive predictive value 88.1% and negative predictive value 92.8% for predicting the presence of Staphylococcus aureus in culture (p < 0.001).ConclusionsA tracheal aspirate Gram stain can be used to rule out the presence of Staphylococcus aureus in patients with a clinical diagnosis of VAP with a 92.8% Negative Predictive Value. Therefore, 7.2% of patients with Staphylococcus aureus would not be protected by an empiric treatment that limits antimicrobial coverage to Staphylococcus aureus only when Gram positive cocci in clusters are identified.

Haemophilus Species Bacteremia in Adults in the 21st Century

Introduction Haemophilus bacteremia (HB) has historically been a pediatric disease. With the advent of conjugated Haemophilus influenzae type B pediatric vaccination, morbidity and mortality of HB was decreased in both the pediatric and adult populations. To understand the current epidemiology and pathogenicity of HB in adults, we reviewed the medical records of all adult patients with HB at our 577-bed adult hospital from January 1, 2001 to December 31, 2012. Methods We reviewed the medical records of all adult patients (≥16 years of age) with Haemophilus species bacteremia at our institution during the 11-year period from January 1, 2001 to December 31, 2012 and reported the epidemiology, source of infection, comorbid conditions, treatment, and mortality of HB for these patients. Results There were 45 cases of HB during the study period. Thirty-nine cases (86.7%) were caused by H. influenzae and 6 cases (13.3%) were caused by Haemophilus parainfluenzae. There were 21 episodes in women (46.7%) and 24 episodes in men (53.3%). The patients’ ages ranged from 20 to 91 years with a mean of 69.6 years and a median of 70 years. The eighth (11 cases, 24.4%) and ninth (13 cases, 28.9%) decades had the highest occurrence of HB. Pneumonia was by far the most common presentation (31 cases, 68.9%), followed by biliary sepsis (4 cases, 8.9%), and skin and soft tissue infections (3 cases, 6.7%). The most common initial therapy for these patients was either an anti–pneumococcal fluoroquinolone or a combination of ceftriaxone and azithromycin, reflecting our institution’s community-acquired pneumonia treatment protocol and order sets. Six of 43 patients died, for a mortality rate of 13.9%. Conclusions Haemophilus species bacteremia is not uncommon in the adult population, is most commonly caused by H. influenzae (86.6%), is most prevalent in the eighth and ninth decades of life, and has a significant mortality rate (13.3%) despite the uniformly appropriate initial empiric antimicrobial therapy. Pneumonia is the most common presenting manifestation causing 68.9% of all cases of HB in our series.

Microbial Isolates and Their Antimicrobial Susceptibilities in Inframalleolar Foot Infections

Foot infections are especially common among diabetic individuals and often contribute to limb loss. We investigated the microbiology of foot infections in our hospital to further understand the microbes involved and to assist in identifying potential empiric oral antibiotic regimens for foot infections. All moderate/severe inframalleolar foot infections that were drained surgically at a single center during a single calendar year were included. Initial isolates obtained intra-operatively were reviewed. A total of 39 patients underwent operative drainage, of whom 34 (87%) had diabetes mellitus. Fifty-two total specimens were obtained, consisting of 26 fluid swabs, 12 soft-tissue specimens, and 11 bone specimens. Nineteen (49%) of the specimens were obtained from toe wounds, 16 (41%) from forefoot wounds, two (5%) from midfoot wounds, and two (5%) from heel wounds. Most specimens (71%) were polymicrobial, yielding a mean of 2.2 isolates. In all, 100 individual isolates, encompassing 39 different bacterial organisms, were identified (55 gram-positive aerobes, 33 gram-negative aerobes, 11 anaerobes, and one fungus). Enterococcus species and Staphylococcus aureus were the most common bacteria, each representing 13% of isolates. Only 9% of isolates were methicillin-resistant S. aureus. Obtaining multiple specimens (e.g., both fluid and tissue) increased the yield for identification of organisms. Oral antibiotics provided adequate coverage for gram-positive organisms but not for gram-negative organisms. Foot infections are typically polymicrobial and may involve a wide variety of microbes. Initial gram-stain results could be used to choose better initial empiric antimicrobial therapy for such infections.

Infections in acute leukemia in Indian Children

Aims: In the present study acute leukemic children were studied to determine the incidence and principal site of infection, correlation with absolute neutrophil count, causative organisms and to standardize the initial empirical anti microbial therapy. Materials and methods: A total 40 children in the age group 6 month to 12 year with acute leukemia relapse were included in this study. A total 82 infectious episodes including 61 febrile episodes were investigated for infectious etiology. Results: We found that the frequency of infections increased significantly with the degree of immunocompromisation specially neutropenia (ANC &lt; 500/cmm). The skin and soft tissue was the commonest site of infection (26.83%), followed by respiratory tract (21.95%). Staphylococcus nonhemolytic coagulase-negative (34%), followed by Klebsiella (17%) were the most common organisms isolated from blood. Staphylococcus non-hemolytic coagulase-negative was also the commonest isolate (26%) from other sites of infection. Most strains were sensitive to Cloxacillin, cephalosporin and aminoglycosides. Conclusion: For the treatment of febrile episodes, empirical use of beta-lactamase resistant penicillin e.g. Cloxacillin or cephalosporin combined with an aminoglycosides with a broad spectrum antifungal like fluconazole in selective cases at the first sign of infection is recommended. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-1, 40-47 DOI: http://dx.doi.org/10.3126/jcmsn.v9i1.9672

Bacteremia in patients receiving TNF-alpha antagonists – A prospective multicenter study

TNF-alpha antagonists have changed the outcome of various chronic inflammatory diseases. Their use has spread widely and many patients receive those treatments for years. Previous reports found that the use of TNF-alpha antagonists may be associated with an increased risk of serious bacterial infections. We report 47 prospective bacteremia cases from the RATIO registry. A national prospective study was conducted in France between 2004 and 2007 to collect severe bacterial infections in patients receiving TNF-alpha antagonists. All reported cases of bacteremia were validated by an expert committee. Forty-seven bacteremic episodes were reported. Staphylococcus aureus represented the most frequent causative pathogen (40%) and was mostly associated with bones and/or joints infections (68%) and with a worse outcome compared to that observed with other bacterial pathogens. Patients receiving TNF-alpha antagonists may develop bacteremia and S. aureus has to be included in the spectrum of the initial empiric antimicrobial therapy.

P010: Bloodstream infections by drug-resistant organisms in a secondary hospital

DR-BSI caused by Acitetobacter carbapenem resistant and 3 DR-BSI by P. aeruginosa carbapenem resistant. Median time to diagnosis for DR-Nosocomial BSI was 14 days (IQR), 7-35 days after hospital admission. For Gram-negative was 11 days (7.5-31.5) and for Grampositive 19 days (7-29). Only 31.7% of DR-BSI received appropriate initial empirical antimicrobial therapy versus 73.5% of non DR-BSI (p<0.001). More than one third (36.5%) of the episodes occur with significant systemic response (severe sepsis or septic shock). The crude mortality rate was 25.4 % (p<0.001). If the patient developed severe sepsis or septic shock crude mortality rose to 52.2%. Conclusion

Inappropriate empirical antimicrobial therapy for multidrug-resistant organisms in critically ill patients with pneumonia is not an independent risk factor for mortality: Results of a prospective observational study of 758 patients.

The benefits of broad-spectrum initial empirical antibiotic therapy for all patients in intensive care units (ICUs) with high rates of multidrug-resistant organisms (MDROs) have not been critically evaluated. In this study, 758 ICU patients with pneumonia were prospectively evaluated. Of 349 positive respiratory cultures, 119 (34.1%) were with MDRO isolates. These were associated with increased mortality [adjusted hazard ratio (HR)=1.65, 95% confidence interval (CI) 1.01-2.68; P=0.04] as was increasing age and Acute Physiology and Chronic Health Evaluation (APACHE) II score. Among the patients with MDRO-associated pneumonia, increasing age, APACHE II score and inappropriate definitive antimicrobial therapy (IDAT) were found to be significant risk factors for mortality (in-ICU mortality, adjusted HR=2.8, 95% CI 1.3-5.8; P=0.007), but inappropriate empirical antimicrobial therapy (IEAT) was not (in-ICU mortality, unadjusted HR=1.6, 95% CI 0.7-3.6; P=0.3). In conclusion, we found that among critically ill patients with MDRO-associated pneumonia, IEAT is not an independent risk factor for ICU mortality. Hence, we do not recommend the use of broad-spectrum initial empirical antimicrobial therapy for all patients, as its benefits may not outweigh the potential risks. Early microbiological diagnosis to facilitate implementation of early definitive antimicrobial therapy through use of novel technologies is likely to have a major impact.

Acinetobacter is the most common pathogen associated with late-onset and recurrent ventilator-associated pneumonia in an adult intensive care unit in Saudi Arabia

The guidelines for initial empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) are highly dependent on the type of causative pathogen and the time of diagnosis. The objective of this study was to examine the microbial causes of VAP and describe any variability by the timing of VAP onset and over time. A prospective surveillance study was conducted in the adult general intensive care unit of a tertiary care hospital in Riyadh, Saudi Arabia. Microbial isolates obtained from blood and different respiratory specimens of patients diagnosed with VAP (using the US Centers for Disease Control and Prevention definition) between August 2003 and June 2009 were included. A total of 457 pathogens were identified during the study; 380 (83.2%) were associated with primary VAP and 77 (16.8%) were associated with recurrent VAP. Of primary VAP pathogens, 159 (41.8%) were associated with early-onset (<5 days) and 221 (58.2%) were associated with late-onset (≥5 days) VAP. The most common pathogen identified was Acinetobacter spp (26.5%), followed by Pseudomonas aeruginosa (21.7%), Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) (15.3%), Klebsiella spp (6.8%), Haemophilus spp (6.1%), and Enterobacter spp (5.0%). Acinetobacter spp and MRSA were significantly associated with late-onset VAP while Haemophilus spp and Streptococcus pneumoniae were significantly associated with early-onset VAP. Acinetobacter spp was the only pathogen associated with recurrent VAP and its incidence showed a significant increasing trend during the study period. Acinetobacter spp was significantly associated with prolonged ventilation, sedation, and nasogastric intubation. Acinetobacter baumannii is the most common and increasingly important pathogen associated with VAP in our patients, especially late-onset and recurrent VAP.

Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis

It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315)

Meningites à streptocoque du groupe A

An increased incidence and severity of invasive group A streptococcus (GAS) infections over the past decade have been reported by several authors, but GAS remains an uncommon cause of bacterial meningitis. The aim of this study was to describe and analyze the clinical and biological data of GAS meningitis by reporting 10 new cases of pediatric GAS meningitis and making a literature review. The mean age of patients, seven girls and three boys, was 3 years. There was a history of preexisting or concomitant community-acquired infection in five patients over 10. The outcome was fatal in two cases. All patients received an initial empirical antimicrobial therapy with a third generation cephalosporin switched in six cases to amoxicillin. The prognosis for this type of streptococcal meningitis is usually good, but death may occur even in children without any identified risk factor for severe infection.

Prevalence and outcome of cirrhosis patients admitted to UK intensive care: a comparison against dialysis-dependent chronic renal failure patients: Reply to comments by Mason and Yeoman

Dear Editor, We thank Drs Mason and Yeoman for their comments on our paper [1] as these raise a number of very interesting points. However, we would challenge the statement that these points mitigate against our conclusions. As mentioned in the previous reply to Drs Berry and Thompson [2], we do not wish to be seen as champions of nihilism for patients with cirrhosis; rather, our pessimistic conclusions simply reflect the data presented. Indeed, despite improvements in many aspects of critical care over the last 20 years, ICU mortality rates associated with cirrhosis remain very high. We felt that it was time for a change in the message from ‘‘we must try harder’’ to something bolder. It is very hard to advocate continuing ICU care when mortality rates exceed 85–90 %, especially as the vast majority of patients will not be eligible for transplantation. We perhaps should have added a section about optimising pre-ICU care and feel the authors’ critical care bundle suggestion has considerable merit, although whether this would have a benefit on mortality rates remains of course uncertain. However, the suggestion that cirrhosis patients be admitted earlier to the ICU is simplistic and naive given that using Hospital Episode Statistic data we identified [100,000 patients admitted to UK hospitals 2010–2011 with complications of cirrhosis (http://www. hesonline.nhs.uk). As an alternative, we would suggest borrowing another approach from sepsis studies—that of early ‘‘goal-directed therapy’’ [3], either in the emergency room or on the acute admissions ward. Indeed, a recent study has demonstrated that delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality in cirrhosis [4]. As we acknowledge in our paper, the comparison with renal replacement therapy is imperfect, and we again refer to this in our reply to Drs Berry and Thompson [2], However, this hardly mitigates against our conclusion that cirrhosis patients with organ failure have an extremely poor prognosis. Rather than labour this point, we would refer these authors to the very similar overall mortality (59.2 %) seen in patients with haematological malignancies admitted to ICU [5], as mentioned in our discussion; this is a group we hope that all will agree can be regarded as having a poor prognosis. We cannot agree that using the Intensive Care National Audit & Research Centre (ICNARC) database to examine the largest cohort of ICU admissions with liver cirrhosis reported to date can be regarded as a study weakness. We acknowledge in our discussion that neither the Acute Physiology and Chronic Health Evaluation II (APACHE II) nor ICNARC score contains information directly relating to liver failure and conclude that neither score can guide decision-making; however, the area under the receiver operating characteristic curve (AUROC) of 0.8 that is seen with the ICNARC score is comparable to that obtained using Sequential Organ Failure Assessment (SOFA) and Organ System Failure (OSF) models in other studies. Equally, the fact that these scores under-predicted mortality had not been reported before, and we thought it worthy of mention. Again, we do acknowledge in the paper that mortality associated with variceal bleeding has improved over time; as such, a breakdown of mortality associated with differing reasons for admission may have proved interesting. However, the key determinants of ICU mortality in patients with cirrhosis are sepsis and organ failure [6] and, therefore, the aim of the study was to examine these in detail.

Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies

Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent pathogens. However, little is known about their emergence in patients with hematologic malignancies. We identified 18 patients with hematologic malignancies over 3.5 years who developed bloodstream infections (BSIs) caused by CRE. Fourteen BSIs were caused by Klebsiella pneumoniae, three by Enterobacter cloacae, and one was polymicrobial. Initial empirical antimicrobial therapy was active in two patients (11%), and a median of 55 h elapsed between culture collection and receipt of an active agent. Ten patients (56%) died, including nine (69%) of 13 neutropenic patients, with a median of 4 days from culture collection until death. CRE isolates were analyzed for carbapenemase production, β-lactamase genes and outer membrane porin deletions and characterized by multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Carbapenem resistance mechanisms included Klebsiella pneumoniae carbapenemase production and CTX-M-15 production with an absent outer membrane porin protein. No isolate had ≥95% homology on PFGE, indicating a heterogeneous, non-outbreak population of isolates. CRE BSIs are emerging in patients with hematologic malignancies and are associated with ineffective initial empirical therapy, long delays in administration of active antimicrobials and high mortality rates. New diagnostic, therapeutic and preventive strategies for CRE infections in this vulnerable population are needed.

Supratentorial and infratentorial brain abscess

Dear Editor, We would like to make the following observations, on the basis of our personal experience, in relation to the recent article by Landriel et al. [3] on supratentorial and infratentorial brain abscesses. First, the authors include a toxoplasmosis case within the group of abscesses studied. Toxoplasmosis is a disease caused by an obligate intracellular protozoal parasite, Toxoplasma gondii; it is the most common cause of focal brain lesions in patients with AIDS. In this cases, the clinical, radiological and pathological characteristics are different from those of bacterial infection, and for this reason they are not usually included in the literature on brain abscesses [4]. Secondly, the authors report only six paediatric cases. In our experience and in the literature review, paediatric cases represent 15-25 % of all cases treated. Perhaps the authors could indicate if the low percentage is due to circumstances specific to their hospital catchment area [1, 2]. We are struck by the fact that the authors use so many different approaches in the treatment of brain abscess (up to 15 different antibiotic treatment protocols). Our own local protocol for initial empirical antimicrobial therapy includes a combination of vancomycin, third-generation cephalosporin and metronidazole. Between 3 and 5 days later, we either continue with the same treatment or modify it according to the literature and the results of sensitivity tests [1]. Finally, we are surprised by the low percentage of negative cultures obtained. In most of the literature, and in our own experience, negative results represent 15-30 % of all cultures [1, 2, 4]. Perhaps the authors could indicate what accounts for this low percentage.

High Prevalence of Multidrug-Resistant Nonfermenters in Hospital-acquired Pneumonia in Asia

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remain important causes of morbidity and mortality. Increasing antimicrobial resistance has aroused the concern of the failure of antibiotic treatment. To determine the distribution of the bacterial isolates of HAP and VAP, their antimicrobial resistance patterns, and impact of discordant antibiotic therapy on clinical outcome in Asian countries A prospective surveillance study was conducted in 73 hospitals in 10 Asian countries from 2008-2009. A total of 2,554 cases with HAP or VAP in adults were enrolled and 2,445 bacterial isolates were collected from 1,897 cases. Clinical characteristics and antimicrobial resistance profiles were analyzed. Major bacterial isolates from HAP and VAP cases in Asian countries were Acinetobacter spp., Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae. Imipenem resistance rates of Acinetobacter and P. aeruginosa were 67.3% and 27.2%, respectively. Multidrug-resistant rates were 82% and 42.8%, and extensively drug-resistant rates were 51.1% and 4.9%. Multidrug-resistant rate of K. pneumoniae was 44.7%. Oxacillin resistance rate of S. aureus was 82.1%. All-cause mortality rate was 38.9%. Discordant initial empirical antimicrobial therapy increased the likelihood of pneumonia-related mortality (odds ratio, 1.542; 95% confidence interval, 1.127-2.110). Acinetobacter spp., P. aeruginosa, S. aureus, and K. pneumoniae are the most frequent isolates from adults with HAP or VAP in Asian countries. These isolates are highly resistant to major antimicrobial agents, which could limit the therapeutic options in the clinical practice. Discordant initial empirical antimicrobial therapy significantly increases the likelihood of pneumonia-related mortality.

Risk factors for mortality in patients with Burkholderia cepacia complex bacteraemia

Over the last 2 decades, Burkholderia cepacia complex has emerged as a serious human pathogen, especially in critically ill patients. B. cepacia complex has been associated with increased morbidity and mortality in intensive care unit patients. However, in our literature search, we could not find studies on risk factors for mortality in patients with B. cepacia complex bacteraemia. Therefore, we investigated risk factors for mortality in B. cepacia complex bacteraemia. Clinical characteristics and laboratory parameters of 27 patients with 1 or more blood cultures positive for B. cepacia complex from January 2006 to October 2010 in Severance Hospital, Yonsei University College of Medicine, Korea were retrospectively analyzed. The main outcome measure was overall 28-day mortality. Appropriate initial empirical antimicrobial use was defined as administration of agent(s) to which the organism was susceptible within 24 h of obtaining blood for culture. The overall 28-day mortality rate was 41% (11/27). In univariate analysis, underlying diabetes mellitus (p = 0.033), inappropriate initial empirical antimicrobial therapy (p = 0.033), and an elevated Sequential Organ Failure Assessment (SOFA) score (p = 0.002) were significantly associated with mortality. In multivariate analysis, inappropriate initial empirical antimicrobial therapy and an elevated SOFA score were independent risk factors for increased mortality (p = 0.032 and p = 0.028, respectively). An elevated SOFA score and inappropriate initial empirical antimicrobial therapy were significantly associated with adverse outcome in patients with B. cepacia complex bacteraemia.

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP. We retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group. Compared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7mmol/L, respiratory rate >30/min, low blood pressure (systolic <90mmHg or diastolic <60mmHg), age >65 years (CURB-65)≥3, creatinine>1.6mg/dL, C-reactive protein≥100mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1×10(4)/μL, and higher hospital mortality rates. Inadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB≥3 and C-reactive protein≥120mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1×10(4)/μL were independent risk factors for carbapenem resistance.

Spectrum of early-onset and late-onset bacteremias after liver transplantation: Implications for management

Bacteremia is a significant cause of morbidity and mortality after liver transplantation. The characterization of the microbiological spectrum of bacteremia after liver transplantation may help physicians in choosing the initial empirical antimicrobial therapy for patients presenting with sepsis. The clinical and microbiology records of patients who received liver transplantation from January 1997 to March 2006 were reviewed. One hundred twenty-three of the 737 liver recipients (16.7%) developed bacteremia during the median follow-up period of 5.8 years (interquartile range = 2.5-8.8 years); 92 patients (12.5%) had gram-positive bacteremia (GPB), whereas 47 (6.4%) had gram-negative bacteremia (GNB). Nosocomial bacteremia was significantly more frequent among patients with early-onset GPB or GNB versus patients with late-onset GPB (66.7% versus 23.7%, P < 0.001) or GNB (70.6% versus 20.0%, P = 0.001). Peritonitis (33.3% versus 7.9%, P = 0.004) and wound infections (13.0% versus 0%, P = 0.04) as sources were more common in patients with early-onset GPB versus patients with late-onset GPB. Likewise, peritonitis was a more common source of early-onset GNB than late-onset GNB (41.2% versus 6.7%, P = 0.007). Staphylococcus aureus and Enterococcus faecium were the most common pathogens in patients with early-onset GPB, whereas Enterococcus faecalis and Streptococcus species were most common in patients with late-onset GPB. Pseudomonas aeruginosa and anaerobes were the most common pathogens in patients with early-onset GNB, whereas Escherichia coli was most common in patients with late-onset GNB. In conclusion, the microbiological spectra of early-onset and late-onset bacteremias differ, and this should be considered by those determining the initial empirical treatment of liver transplant recipients suspected to have bacteremias.

De-escalation of antimicrobials in the treatment of bacteraemia due to antibiotic-sensitive pathogens in immunocompetent patients

The aim of this study was to examine the safety and efficacy of de-escalating antimicrobial therapy in immunocompetent patients presenting with bacteraemia due to antibiotic-sensitive pathogens. We screened 1,350 positive blood cultures identified in a single, 1,065-bed university hospital over 5 years, and retained 310 cases of bacteraemia due to antibiotic-sensitive pathogens, including (1) methicillin-sensitive staphylococci, (2) penicillin-sensitive streptococci, (3) β-lactam-sensitive (a) Escherichia coli, and (b) Klebsiella species. The efficacy of appropriate initial empirical antimicrobial therapy, the performance of de-escalated pathogen-directed therapy, and the safety and efficacy of de-escalated therapy were evaluated. Among 270 appropriately treated patients, 16 (6%) died, versus 6 (15%) among 40 who were inappropriately treated (p = 0.04). While 201 of 270 patients (74%) who received appropriate initial empirical therapy were candidates for de-escalation, the treatment was de-escalated in only 79 (39%). De-escalation was associated with (1) a trend toward a lower (a) death rate (1 vs. 5%) and (b) treatment failure (4 vs. 10%), and (2) (a) a 4-day longer median duration and (b) a $50 higher median cost of antimicrobial therapy (p < 0.001). When the pathogen was sensitive to antimicrobial therapy and the initial empirical treatment was effective, de-escalation of antimicrobial therapy in immunocompetent patients with bacteraemia was safe and associated with acceptable outcomes. The rate of de-escalation of antimicrobial therapy was low.

Lessons Learned from Surveillance of Antimicrobial Susceptibilities of Pseudomonas aeruginosa at a Large Academic Medical Center.

This research report assessed the differences in resistance rates and antimicrobial usage-versus-susceptibility relationships of Pseudomonas aeruginosa found in various hospital patient care areas. A simplified case control study was also performed to identify patient-specific risk factors associated with cefepime-resistant P. aeruginosa isolates. Last, we determined the consequence of combining mucoid and non-mucoid derived antimicrobial susceptibilities of P. aeruginosa into hospital antibiograms. Overall, susceptibility rates remained lower in the intensive care units (ICUs) compared to the non-ICU patient care areas, except for cefepime over the last time period. Cefepime utilization and antimicrobial-resistance rates among P. aeruginosa isolates had a significant relationship. Decreased meropenem exposure was associated with lower resistance rates relative to cefepime. Risk factors independently associated with cefepime-resistant P. aeruginosa were structural lung disease, ICU admission, recent third generation cephalosporin use, frequent hospital admission and non-urine isolates. Large and statistically significant differences were observed between non-mucoid and combined percent susceptibility data for aminoglycosides. To control antimicrobial resistance and optimize initial empiric antimicrobial therapy, antimicrobial susceptibility and utilization patterns in specific patient care areas should be monitored and risk factors for antimicrobial resistance should be assessed. Mucoid strains of P. aeruginosa should not be included into antimicrobial susceptibility data as this may underestimate activity of most antipseudomonal agents.