Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15–1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16–0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13–0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35–5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann–Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152–1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94–445) for patients with fever of unknown origin, 177 pg/ml (IR, 142–208) for patients with non-microbial fever and 942 pg/ml (IR, 181–2,807) for patients with bacteremia. Using the Mann–Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.     

Risk Factors for the Development of Extended-Spectrum Beta-Lactamase-Producing Bacteria in Nonhospitalized Patients

Although the risk factors for acquiring infection by extended-spectrum beta-lactamase (ESBL)-producing bacteria have been investigated in hospitalized patients, such risk factors have not been defined in the community setting. In this study, clinical data from a total of 311 nonhospitalized patients with community-acquired urinary tract infection (128 with ESBL-positive strains and 183 with ESBL-negative strains) were obtained. According to a multivariate analysis, the following were identified as independent risk factors: previous hospitalization in the past 3 months (OR=8.95, 95%CI, 3.77–21.25), antibiotic treatment in the past 3 months (OR=3.23, 95%CI, 1.76–5.91), age over 60 years (OR=2.65, 95%CI, 1.45–4.83), diabetes (OR=2.57, 95%CI, 1.20–5.51), male gender (OR=2.47, 95%CI, 1.22–5.01), Klebsiella pneumoniae infection (OR=2.31, 95%CI, 1.17–4.54), previous use of third-generation cephalosporins (P=0.014, OR=15.8, 95%CI, 1.7–143), previous use of second-generation cephalosporins (P<0.0001, OR=10.1, 95%CI, 4.2–24), previous use of quinolones (P=0.001, OR=4.1, 95%CI, 1.8–9.0), and previous use of penicillin (P=0.003, OR=4.0, 95%CI, 1.6–9.0).     

Serum adenosine deaminase and procalcitonin concentrations in neutropenic febrile children with acute lymphoblastic leukaemia

Abstract Neutropenia as a state of immunosuppression is probably the major problem in patients suffering from acute lymphoblastic leukaemia undergoing intensive chemotherapy. Fever is frequent in neutropenic patients and often related to infection. Clinically, the presence of infection in patients with neutropenia may be difficult to establish, because there are usually few signs of infection. The aim of this work was to study sensitive markers for early diagnosis of microbial infection in neutropenic children undergoing intensive chemotherapy as a treatment for acute lymphoblastic leukaemia. The study included three groups (A, B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A consisted of 29 children with febrile neutropenia and microbial infection, aged 1–14 years (5.8±2.9), 11 boys and 18 girls; Group B of 38 children with febrile neutropenia without microbial infection, aged 2–14 years (6.8±3.1), 14 boys and 24 girls; and Group C of 53 children with neutropenia without fever and without infection, aged 1–14 years (5.9±2.1), 21 boys and 32 girls. Blood samples were collected upon admission and before the start of any antimicrobial treatment. The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C–reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA–1 and ADA–2. According to our results the procalcitonin levels and total ADA activity discriminated best between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes (Group C). In conclusion, this study suggests procalcitonin and total ADA activity as two easily measurable and cost effective markers for the assessment of immune response in febrile neutropenic patients with acute lymphoblastic leukaemia.     

Cytokine production in a whole-blood assay after Epstein-Barr virus infection in vivo.

Epstein-Barr virus (EBV) has a marked tropism for cells of the immune system, and infection can result in profound immunomodulatory effects. In order to examine the role of cytokines during the acute phase of infectious mononucleosis, we studied the levels of different interleukins (ILs), interferons (IFNs), and the soluble IL-2 receptor (sIL-2R) in serum samples of 20 patients. We found elevated levels of IL-2, IL-6, sIL-2R, and IFN-gamma. Whereas the peak of IL-2 and IL-6 concentration occurred during the first week (P < 0.01), the largest amounts of sIL-2R were measured during the second week (P < 0.01). IFN-gamma levels were only enhanced during the first week. In addition, we investigated the ability to produce cytokines in response to mitogenic stimulation in a whole-blood assay of 11 patients compared with healthy blood donors. In the whole-blood assay of patients compared with controls after stimulation with lipopolysaccharide, we measured more than 10-fold elevated levels of tumor necrosis factor alpha (P < 0.01), 3-fold elevated levels of IL-1 beta (P < 0.01), and about 2-fold increased amounts of IL-6 (P < 0.01). A significant enhancement in sIL-2R and IFN-gamma concentration was found in the assay after stimulation with phytohemagglutinin after 24 h of incubation (P < 0.01). Collectively, our data seem to indicate that monocytes are strongly activated during infectious mononucleosis. Monocytes and monocyte-derived factors may play an important role in the pathogenesis of infectious mononucleosis and, together with T lymphocytes, may be partly responsible for clinical symptoms.     

Association of secondary and polymicrobial nosocomial bloodstream infections with higher mortality

The objective of this study was to characterize microbiological factors independently associated with higher mortality rates following nosocomial bloodstream infection. All patients admitted to the University of Iowa Hospitals and Clinics between 1 July 1989 and 30 June 1990 who developed a nosocomial bloodstream infection were included. The crude in-house mortality for the 364 patients with nosocomial bloodstream infections was 33 %. These deaths accounted for 25 % of all in-hospital deaths. Significant risk factors for death from bloodstream infection included diagnoses of cancers and diseases of the cardiovascular and respiratory systems (p<0.01). Neither previous surgery nor neutropenia was associated with higher mortality rates. Whereas the crude mortality rates associated with gram-negative (33 %) and gram-positive (31 %) bloodstream infections were similar, that associated with fungemia was higher (54 %, p<0.02). The mortality associated with secondary bloodstream infections (46 %) was higher than that associated with primary bloodstream infections (28 %, p<0.001). Furthermore, polymicrobial infections had a worse prognosis than infections from which a single pathogen was isolated (p<0.05). A multivariate, logistic regression model identified four variables that independently predicted mortality (p=0.025): age (OR 1.01 per year; CI95 1.00–1.02); cancer (OR 2.35, CI95 1.26–4.37) or diseases of the cardiovascular or respiratory systems (OR 2.20, CI95 1.04–4.67); polymicrobial infection (OR 2.34; CI95 1.21–4.53); and secondary bloodstream infection (OR 2.46; CI95 1.50–4.02). The last variable was the strongest independent predictor. Our study demonstrates the importance of microbiological factors in the outcome of nosocomial bloodstream infections.     

Accuracy of blood culture for early diagnosis of mediastinitis in febrile patients after cardiac surgery

Postsurgical mediastinitis (PSM) remains a major cause of morbidity and mortality in patients undergoing cardiac surgery procedures. Although prompt diagnosis is crucial in these patients, neither clinical data nor imaging techniques have shown enough sensitivity or specificity for early diagnosis of PSM. The aim of the present study was to assess the validity of blood cultures as a diagnostic test for the early detection of PSM in patients who become febrile after cardiac surgery procedures. During a 4-year period (1999–2002), patients who developed fever (>37.8°C) in the first 60 days after a cardiac surgery procedure were evaluated. Blood cultures were drawn from these patients. PSM was defined as deep infection involving retrosternal tissue and/or the sternal bone directly observed by the surgeon and confirmed microbiologically. Three criteria for positivity of blood cultures were applied: bacteremia, staphylococcal bacteremia, or Staphylococcus aureus bacteremia. For purposes of the analysis, a positive blood culture in patients with PSM was considered a true-positive test and a negative blood culture a false-negative test. Otherwise, in febrile patients without PSM in the postsurgery period, a positive blood culture was considered a false-positive test and a negative blood culture a true-negative test. Blood cultures were drawn from 266 febrile patients in the postsurgery period. PSM occurred in 38 patients (26 cases due to S. aureus, 8 to Staphylococcus epidermidis, 3 to gram-negative enteric bacteria, and one to Pseudomonas aeruginosa). Within the 60-day postsurgical period, blood culture as a diagnostic test was most accurate in patients with S. aureus bacteremia, providing 68% sensitivity, 98% specificity, a positive predictive value of 87%, and a negative predictive value of 95%. If the analysis was limited to the period during which patients are at maximum risk for PSM (day 7–20), the values in patients with S. aureus bacteremia were as follows: 73% sensitivity, 98% specificity, 90% positive predictive value, and 93% negative predictive value. Blood culture is an accurate test for the early diagnosis of PSM in febrile patients after cardiac surgery, particularly in institutions where S. aureus is prevalent in this context. A negative blood culture practically excludes PSM and, during the period of maximum risk for PSM, the presence of S. aureus bacteremia should compel early surgical management.Presented in part at the 43rd Interscience Conference of Antimicrobial Agents and Chemotherapy in Chicago, September 14–17, 2003, slide session K-1300.     

Flucloxacillin treatment of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> meningitis

In this paper, we aimed to evaluate the efficacy of flucloxacillin treatment of meningitis caused by methicillin-sensitive Staphylococcus aureus. We identified 33 patients with meningitis due to S. aureus; eight had community-acquired meningitis and 25 had neurosurgical meningitis. Six of the eight patients with community-acquired meningitis were cured. Eighteen of the 22 patients treated with flucloxacillin were cured without relapse (86%, 95%CI 65–97%) and their cerebrospinal fluid (CSF) cultures were sterile after a median of 3 days of treatment. The cure rate for 12 patients who also received an additional antibiotic at the outset of treatment was 75% (95%CI 43–95%). This was not different to the cure rate for the ten patients who received flucloxacillin alone 90% (95%CI 56–100%). We conclude that flucloxacillin is an effective treatment for meningitis caused by S. aureus.     

Elevated procalcitonin as a diagnostic marker in meningococcal disease

Patients with meningococcal disease who seek medical attention can create a diagnostic dilemma for clinicians due to the nonspecific nature of the disease’s presentation. This study assesses the diagnostic accuracy of procalcitonin levels in the setting of meningococcal disease. Two emergency department cohorts (A and B) were studied between 2002 and 2005, during the current epidemic of serogroup B meningococcal disease in New Zealand. Cohort A consisted of 171 patients, all with confirmed meningococcal disease (84 children, 87 adults). Cohort B consisted of a large (n=1,524) consecutively recruited population of febrile patients who presented to the emergency department, 28 of whom had confirmed meningococcal disease. Within the meningococcal disease cohort (cohort A), the geometric mean procalcitonin level was 9.9 ng/ml, with levels being higher in children than in adults (21.6 vs. 4.6 ng/ml, p=0.01). The overall sensitivity of elevated procalcitonin, using a cutoff of 2.0 ng/ml in children and 0.5 ng/ml in adults, was 0.93 (95%CI: 0.88–0.96). Despite the higher cutoff level for paediatric patients, a trend towards greater sensitivity existed in children (0.96 vs. 0.90; p=0.08). Elevated procalcitonin was correlated with whole blood meningococcal load (r=0.50) and Glasgow Meningococcal Sepsis Prognostic Score (r=0.40). Within the cohort of patients who were febrile on presentation (cohort B), the specificity of elevated procalcitonin in meningococcal disease was 0.85 (95% CI: 0.83–0.87), the positive and negative likelihood ratios were 6.1 and 0.08, respectively, and the sensitivity of elevated procalcitonin (0.93; 95% CI: 0.76–0.99) was corroborated. Measurement of procalcitonin is a useful tool in patients with nonspecific febrile illnesses when the possibility of meningococcal disease is present. The diagnostic accuracy surpasses that of current early laboratory markers, allowing results to be used to guide decisions about patient management.     

Febrile response induced by cecal ligation and puncture (CLP) in rats: involvement of prostaglandin E<Subscript>2</Subscript> and cytokines

The purpose of the present study was to better understand the events involved in the febrile response induced by cecal ligation and puncture (CLP), a complex infectious process. To this end, we conducted in vivo experiments in rats examining (1) fever development, (2) bacterial number in the infection focus and in blood, (3) peripheral and hypothalamic synthesis of cytokines, (4) hypothalamic and cerebrospinal fluid (CSF) synthesis of prostaglandin E₂ (PGE₂), (5) the effect of anti-IL-6 antibody on fever, and (6) the effect of celecoxib on fever and hypothalamic synthesis of PGE₂ after CLP induction. We found that CLP promotes fever and animal death depending on the number of punctures. The peak of CLP-induced fever overlapped with the maximal increase in the number of bacteria in the infectious focus and blood, which occurred at 6 and 12 h. The peak of the febrile response also coincided with increased amounts of interleukin (IL)-1β, IL-6 and IL-10 in the peritoneal exudate and serum; IL-6 in the hypothalamus and PGE₂ in the CSF and predominantly in the hypothalamus. Moreover, intracerebroventricularly injected anti-IL-6 antibody reduced the febrile response while celecoxib reduced the fever and PGE₂ amount in the hypothalamus induced by CLP. Tumor necrosis factor (TNF)-α peaked at 3 h at all sites studied. Conversely, IL-10 concentration decreased in the hypothalamus. These findings show that the peak of CLP-induced fever is accompanied by an increase of bacteria in peritoneal fluid (local infection) and blood; local synthesis of pyrogenic (IL-1β, IL-6) and antipyretic (IL-10) cytokines and central production of IL-6 and PGE₂, suggesting that these last are the central mediators of this response.     

Impact of healthcare-associated acquisition on community-onset Gram-negative bloodstream infection: a population-based study

We performed a population-based study to examine the influence of healthcare-associated acquisition on pathogen distribution, antimicrobial resistance, short- and long-term mortality of community-onset Gram-negative bloodstream infections (BSI). We identified 733 unique patients with community-onset Gram-negative BSI (306 healthcare-associated and 427 community-acquired) among Olmsted County, Minnesota, residents from 1 January 1998 to 31 December 2007. Multivariate logistic regression was used to examine the association between healthcare-associated acquisition and microbiological etiology and antimicrobial resistance. Multivariate Cox proportional hazards regression was used to evaluate the influence of the site of acquisition on mortality. Healthcare-associated acquisition was predictive of Pseudomonas aeruginosa (odds ratio [OR] 3.14, 95% confidence intervals [CI]: 1.59–6.57) and the group of Enterobacter, Citrobacter, and Serratia species (OR 2.23, 95% CI: 1.21–4.21) as causative pathogens of community-onset Gram-negative BSI. Healthcare-associated acquisition was also predictive of fluoroquinolone resistance among community-onset Gram-negative bloodstream isolates (OR 2.27, 95% CI: 1.18–4.53). Healthcare-associated acquisition of BSI was independently associated with higher 28-day (hazard ratio [HR] 3.73, 95% CI: 2.13–6.93) and 1-year mortality (HR 3.60, 95% CI: 2.57–5.15). Because of differences in pathogen distribution, antimicrobial resistance, and outcomes between healthcare-associated and community-acquired Gram-negative BSI, identification of patients with healthcare-associated acquisition of BSI is essential to optimize empiric antimicrobial therapy.     

Evaluation of a latex agglutination test (KAtex) for detection of <Emphasis Type="Italic">Leishmania</Emphasis> antigen in urine of patients with HIV-<Emphasis Type="Italic">Leishmania</Emphasis> coinfection: value in diagnosis and post-treatment follow-up

The usefulness of antigen detection in urine as an alternative tool for diagnosis of leishmaniasis and post-treatment follow-up in patients with Leishmania-HIV coinfection was evaluated with a latex agglutination test (KAtex; Kalon Biological, UK). Forty-nine HIV-infected patients with visceral leishmaniasis were included in the study. Antigen detection in urine (ADU) was positive in 42 of 49 (sensitivity, 85.7%) samples obtained during a primary episode. After treatment, a follow-up study in 23 patients was performed by simultaneous ADU and culture of peripheral blood mononuclear cells in 148 determinations. The two methods gave concordant results in 94 cases, 38 of which were positive and 56 negative. In five cases, ADU was negative and culture of peripheral blood mononuclear cells was positive: two of these cases corresponded to clinical relapses. In 49 cases, culture of peripheral blood mononuclear cells was negative and ADU was positive. In the absence of clinical symptoms, the detection of parasite antigens in 71 of 130 (54.6%) urine samples was not associated with clinical disease. The Kaplan-Meier estimates of the probability of relapse at 6, 12, 18, and 24 months were 16% (95%CI, 15–17%), 20% (95%CI, 18–22%), 31% (95%CI, 27–35%), and 71% (95%CI, 52–89%), respectively, in patients with a positive ADU result. In contrast, when ADU was negative, the probability of relapse was 5% at 6 months (95%CI, 2–8%) (only 2 of 11 patients who relapsed had a negative test). ADU by KAtex is appropriate for primary diagnosis of visceral leishmaniasis, for monitoring the efficacy of treatment, and for detection of subclinical infection.     

Seroepidemiological study of Rickettsia felis, Rickettsia typhi, and Rickettsia conorii infection among the population of southern Spain

Rickettsia typhi and Rickettsia conorii, the etiologic agents of, respectively, murine typhus and Mediterranean spotted fever, are recognized as frequent causes of fever of intermediate duration in southern Spain; in addition, in recent years Rickettsia felis has been detected in potential vectors in this area. Nevertheless, limited data exist regarding the actual prevalence of past infection due to these three pathogens. In the present study, the prevalence of past infection due to R. felis, R. typhi, and R. conorii was determined in a representative population of southern Spain during 2002. In addition, the possible risk factors associated with exposure to these pathogens were investigated. An epidemiological survey was completed by all subjects included in the study. Serum samples were tested by indirect immunofluorescence assay. The prevalence of past infection due to R. felis, R. typhi, and R. conorii among the 504 total subjects was 6.5, 3.8 and 8.7%, respectively. In multivariate analysis, infection due to R. felis was independently associated with a high-risk occupation (one that required working outdoors in nature, close contact with domestic animals, or potential contact with rodents) (OR=5.8; 95%CI 2.1–15.6), while infection due to R. typhi was associated with older age (factor of 1.04 [95%CI 1.008–1.068]) and frequent insect bites (OR=10.3; 95%CI 2.3–45.5). Two factors were associated with infection due to R. conorii: a high-risk occupation (OR=9.3; 95%CI 3.7–23.2), and participation in outdoor activities (OR=7.2; 95%CI 1.4–38.5). The results confirm the widespread prevalence of past infection due to R. felis, R. typhi, and R. conorii in the population of southern Spain.     

Voriconazole Salvage Treatment of Invasive Candidiasis

Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1–4 agents), and 83% had received an azole. Manifestations of invasive candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1–314 days). The overall rate of response was 56% (95%CI, 41–70), with the following response rates observed for individual Candida species: Candida albicans, 44% (20–70); Candida glabrata, 38% (14–68); Candida krusei, 70% (35–93); Candida tropicalis, 67% (30–93); and other Candida spp., 100% (40–100). The response rate in patients who had failed previous azole therapy was 58% (42–73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of invasive candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei.This work was presented as abstract no. 352 at the 40th Annual Meeting of the Infectious Diseases Society of America, Chicago, 2002. This work was supported by a grant from Pfizer, Inc.     

Validation of a predictive model for identifying febrile young infants with altered urinalysis at low risk of invasive bacterial infection

In 2015, a predictive model for invasive bacterial infection (IBI) in febrile young infants with altered urine dipstick was published. The aim of this study was to externally validate a previously published set of low risk criteria for invasive bacterial infection in febrile young infants with altered urine dipstick. Retrospective multicenter study including nine Spanish hospitals. Febrile infants ≤90 days old with altered urinalysis (presence of leukocyturia and/or nitrituria) were included. According to our predictive model, an infant is classified as low-risk for IBI when meeting all the following: appearing well at arrival to the emergency department, being >21 days old, having a procalcitonin value <0.5 ng/mL and a C-reactive protein value <20 mg/L. IBI was considered as secondary to urinary tract infection if the same pathogen was isolated in the urine culture and in the blood or cerebrospinal fluid culture. A total of 391 patients with altered urine dipstick were included. Thirty (7.7 %) of them developed an IBI, with 26 (86.7 %) of them secondary to UTI. Prevalence of IBI was 2/104 (1.9 %; CI 95% 0.5–6.7) among low-risk patients vs 28/287 (9.7 %; CI 95% 6.8–13.7) among high-risk patients (p?<?0.05). Sensitivity of the model was 93.3 % (CI 95% 78.7–98.2) and negative predictive value was 98.1 % (93.3–99.4). Although our predictive model was shown to be less accurate in the validation cohort, it still showed a good discriminatory ability to detect IBI. Larger prospective external validation studies, taking into account fever duration as well as the role of ED observation, should be undertaken before its implementation into clinical practice.     

Increased and highly stable levels of functional soluble interleukin-6 receptor in sera of patients with monoclonal gammopathy

Soluble human interleukin-6 receptor (sIL-6R) was measured in the serum of 30 healthy individuals, 32 individuals with monoclonal gammopathy of undetermined significance (MGUS), 20 patients with early multiple myeloma (MM) and 54 patients with overt MM. The serum activity recognized by an immunoradiometric assay was determined to be sIL-6R, because of its binding capacity to IL-6 and its molecular mass of 55 kDa. All sera of healthy individuals contained sIL-6R (mean value: 89 ng/ml, range 17-300 ng/ml). Serum sIL-6R levels were increased by 51% in patients with MGUS (mean value: 135 ng/ml, p<0.005), by 44% in patients with early myeloma (mean value: 128 ng/ml, p<0.001) and by 116 % in patients with overt MM (mean value: 193 ng/ml, p<0.001). In patients with MM, a complete lack of correlation (p>0.7) was found between serum sIL-6R levels and other previously recognized prognostic factors in this disease, particularly serum IL-6 levels and those factors related to tumor cell mass. The independence of serum sIL-6R levels on tumor cell mass was directly demonstrated by studying four patients with MM treated with autologous bone marrow transplantation for periods of between 320 and 760 days. These levels were found to be remarkably stable and constant, independent of whether patients relapsed or achieved complete remission. Finally, physiological concentrations of sIL-6R were found to increase by tenfold the sensitivity of human myeloma cell lines to IL-6. These observations suggest a high control of the sIL-6R level in vivo, and, possibly, an important functional role of this circulating protein in patients with monoclonal gammopathies.     

Effect of inappropriate initial empiric antibiotic therapy on outcome of patients with community-acquired intra-abdominal infections requiring surgery

To assess the significance of initial empiric parenteral antibiotic therapy in patients requiring surgery for community-acquired secondary peritonitis, 425 patients hospitalized between January 1999 and September 2001 in 20 clinics across Germany were followed for a total of 6,521 patient days. Perforated appendix (38%), colon (27%), or gastroduodenum (22%) were the most common sites of infection. Escherichia coli was the most common pathogen. A total of 54 (13%) patients received inappropriate initial parenteral therapy not covering all bacteria isolated, or not covering both aerobes and anaerobes in the absence of culture results. Clinical success, predefined as the infection resolving with initial or step-down therapy after primary surgery, was achieved in 322 patients (75.7%; 95% confidence interval (CI), 70.6–81.2). Patients were more likely to have clinical success if initial antibiotic therapy was appropriate (78.6%; 95% CI, 73.6–83.9) rather than inappropriate (53.4%; 95% CI, 41.1–69.3). Patients having clinical success were estimated to stay 13.9 days in hospital (95% CI, 13.1–14.7), while those who had clinical failure stayed 19.8 days (95% CI, 17.3–22.3). In conclusion, appropriateness of initial parenteral antibiotic therapy was a predictor of clinical success, which in turn was associated with length of stay.     

Role of<Emphasis Type="Italic"> Chlamydia pneumoniae</Emphasis> and<Emphasis Type="Italic"> Mycoplasma pneumoniae</Emphasis> as Causative Agents of Community-Acquired Pneumonia in Hospitalised Children and Adolescents

The aim of the study presented here was to determine the prevalence of Chlamydia pneumoniae versus Mycoplasma pneumoniae infections in paediatric patients with community-acquired pneumonia. A total of 50 patients (mean age, 5.5 years; median, 3.9 years) with community-acquired pneumonia were enrolled. Four patients were found to have Chlamydia pneumoniae infection (1 culture positive, 1 PCR positive and 2 serology positive) and 16 patients had Mycoplasma pneumoniae infection (2 PCR positive, 4 PCR and serology positive, 10 serology positive), including three patients with coinfection. The rates of Mycoplasma pneumoniae infection were 22%, 35% and 40% in children aged 1–3, >3–7 and >7 years, respectively. Acute Chlamydia pneumoniae infection was substantially less common than Mycoplasma pneumoniae infection in our study cohort.This work was presented in part at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Toronto, Canada, 17–20 September 2000 (Poster #588)     

Full-Course Oral Levofloxacin for Treatment of Hospitalized Patients with Community-Acquired Pneumonia

Most guidelines for the management of hospitalized patients with community-acquired pneumonia (CAP) recommend commencing therapy with intravenous antibiotics, primarily because of concern about absorption of oral antibiotics in acutely ill patients. However, patients who respond are rapidly switched to oral therapy, which has been shown to reduce costs and to shorten the length of stay. The aim of the present study was to determine whether a full course of oral antibiotics is as efficacious and as safe as intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized, non-ICU patients with CAP. In an open-labelled, controlled study, 129 hospitalized patients with CAP were randomly assigned in a 2:1 ratio to receive either a full course of oral levofloxacin (500 mg q12 h) or an intravenous-to-oral sequential therapy consisting of intravenous ceftriaxone (2 g q24 h) with or without clarithromycin (500 mg q12 h) followed by an oral antibiotic (a beta-lactam agent in the majority of patients). The primary study endpoint was the resolution of CAP; secondary endpoints included length of stay and overall mortality. CAP resolved in 72 of 79 (91.1%) patients in the levofloxacin group and in 34 of 37 (91.9%) patients in the intravenous-to-oral sequential therapy group (difference, –0.8%, 95%CI, –11.6–10.0). Median length of stay was 8 days (range, 2–74 days) in the levofloxacin group and 10 days (range, 3–29 days) in the intravenous-to-oral sequential therapy group (P=0.28). Day 30 mortality rates were 1.3% (1 of 79) and 8.1% (3 of 37), respectively (difference, –6.8%, 95%CI, –16.0–2.3). Full-course oral levofloxacin is as efficacious and as safe as standard intravenous-to-oral sequential antibiotic therapy for the treatment of hospitalized patients with CAP.     

Economic Impact of<Emphasis Type="Italic"> Candida</Emphasis> Colonization and<Emphasis Type="Italic"> Candida</Emphasis> Infection in the Critically Ill Patient

The objective of the study presented here was to assess the economic impact of Candida colonization and Candida infection in critically ill patients admitted to intensive care units (ICUs). For this purpose, a prospective, cohort, observational, and multicenter study was designed. A total of 1,765 patients over the age of 18 years who were admitted for at least 7 days to 73 medical-surgical ICUs in 70 Spanish hospitals between May 1998 and January 1999 were studied. From day 7 of ICU admission to ICU discharge, samples of tracheal aspirates, pharyngeal exudates, gastric aspirates and urine were collected every week for culture. Prolonged length of stay was associated with severity of illness, Candida colonization or infection, infection by other fungi, antifungal therapy, treatment with more than one antifungal agent, and toxicity associated with this therapy. Compared to non-colonized, non-infected patients (n=720), patients with Candida colonization (n=880) had an extended ICU stay of 6.2 days (OR, 1.69; 95%CI, 1.53–1.87; P<0.001) and an extended hospital stay of 8.6 days (OR, 1.27; 95%CI, 1.16–1.40; P<0.001). The corresponding figures for patients with Candida infection (n=105) were 12.7 days for ICU stay (OR, 2.13; 95%CI, 1.72–2.64; P<0.001) and 15.5 days for hospital stay (OR, 1.23; 95%CI, 0.99–1.52; P=0.060). Candida colonization resulted in an additional 8,000 EUR in direct costs and Candida infection almost 16,000 EUR. Both Candida colonization and Candida infection had an important economic impact in terms of cost increases due to longer stays in both the ICU and in the hospital.     

Long-Term Outcome and Quality of Care of Patients with<Emphasis Type="Italic"> Staphylococcus aureus</Emphasis> Bacteremia

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6–8.9), pneumonia (OR, 3.6; 95%CI, 1.2–10.2), age >60 years (OR, 2.6; 95%CI, 1.5–4.5), and known source of infection (OR, 2.3; 95%CI, 1.3–4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.