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Intravenous lipid emulsions are the major determinant of coagulase-negative staphylococcal bacteremia in very low birth weight newborns.

BACKGROUND: Intravenous lipid emulsions and the i.v. catheters through which they were administered were the major risk factors for nosocomial coagulase-negative staphylococcal (CONS) bacteremia among newborns in our neonatal intensive care units a decade ago. However, medical practice is changing, and these and other interventions may have different effects in the current setting. OBJECTIVES: We determined the independent risk factors for CONS bacteremia in current very low birth weight newborns after adjusting for severity of underlying illness. METHODS: We surveyed 590 consecutively admitted newborns with birth weights < 1500 g hospitalized in 2 neonatal intensive care units and conducted a case-control study in a sample of 74 cases of CONS bacteremia and 74 pairs of matched controls. Adjusted relative odds of bacteremia were estimated for a number of attributes and therapeutic interventions in 2 time intervals before CONS bacteremia: any time before bacteremia and the week before bacteremia. RESULTS: Using conditional logistic regression to adjust for indicators of severity of illness, two procedures were independently associated with subsequent risk of CONS bacteremia at any time during hospitalization: i.v. lipids, odds ratio (OR) = 9.4 [95% confidence interval (CI) 1.2 to 74.2]; and any surgical or percutaneously placed central venous catheter, OR = 2.0 (95% CI 1.1 to 3.9). Considering only the week immediately preceding bacteremia, the independent risk factors were: mechanical ventilation, OR = 3.2 (95% CI 1.3 to 7.6); and short peripheral venous catheters, OR = 2.6 (95% CI 1.0 to 6.5). CONCLUSIONS: During the last decade exposure to i.v. lipids any time during hospitalization has become an even more important risk factor for CONS bacteremia (OR = 9.4). Of these bacteremias 85% are now attributable to lipid therapy. In contrast the relative importance of intravenous catheters as independent risk factors has declined. Mechanical ventilation in the week before bacteremia has emerged as a risk factor for bacteremia.

Bacteremia↗

Liver enzyme abnormalities in gram-negative bacteremia of premature infants.

BACKGROUND: Hyperbilirubinemia and liver enzyme abnormalities are commonly observed in sepsis. However, the frequency in premature neonates and the specific relation to gram-negative bacteria are not known. PATIENTS AND METHODS: Charts of all preterm infants who had positive blood cultures for either gram-negative bacteria or coagulase-negative staphylococci were reviewed. Neonates with gram-negative bacteremia (n = 54) were compared with neonates with coagulase-negative staphylococcal bacteremia (n = 31). In addition infants with gram-negative bacteremia and elevated liver enzymes (n = 25) were compared with infants with gram-negative bacteremia and normal liver enzymes (n = 29). RESULTS: Liver enzyme abnormalities accompanied 46.3% (25 of 54) of gram-negative bacteremia and 12.9% (4 of 31) of episodes of coagulase-negative staphylococcal bacteremia (P = 0.002). Serum concentrations of liver enzymes were significantly higher in infants with gram-negative bacteremia than in those with coagulase-negative staphylococcal bacteremia (P < 0.0001), but no difference in alkaline phosphatase serum values was observed. Infants with gram-negative bacteremia and elevated liver enzymes were not fed for a longer period than infants with gram-negative bacteremia and normal liver enzymes (7.3 +/- 6.3 days vs. 4.0 +/- 4.3 days, P = 0.03), and this was accompanied by significant conjugated hyperbilirubinemia (P < 0.0001). Ventilation, total parenteral nutrition and medications were not responsible for the observed differences. Klebsiella pneumoniae bacteremia was commonly associated with elevated liver enzymes (12 of 18), whereas none of the infants with Pseudomonas aeruginosa bacteremia had elevated liver enzymes. CONCLUSIONS: Gram-negative bacteremia is commonly associated with cholestasis in premature neonates. Liver enzyme abnormalities are more common than elevated conjugated bilirubin, not all gram-negative bacteria have the same effect and the lack of enteral feeding seems to play a more significant role than the administration of parenteral nutrition.

Bacteremia↗

Central venous catheter removal versus in situ treatment in neonates with coagulase-negative staphylococcal bacteremia.

OBJECTIVE: To determine how often neonates with coagulase-negative staphylococcal (CONS) bacteremia can be treated successfully without removing the central venous catheter (CVC). METHODS: A cohort study of CONS bacteremia and CVCs was conducted in infants in a neonatal intensive care unit in a 5-year period (1994 through 1998). CONS bacteremia was defined as at least two positive blood cultures within 3 days of each other. RESULTS: Fifty-six infants had early removal CVC (ER-CVC) within 3 days, and 63 infants had late removal CVC (LR-CVC) >3 days after the first positive blood culture. All cases of CONS bacteremia were treated with vancomycin. There was no significant difference between infants in the ER-CVC and LR-CVC groups in terms of recurrence of bacteremia or case fatalities. CONS bacteremia of >3 days duration was more frequent in LR-CVC patients than ER-CVC patients: 43% vs. 13% (relative risk, 3.4; 95% confidence interval, 1.6 to 7.2). CONS bacteremia was successfully treated without CVC removal in 46% of LR-CVC cases. Seventy-nine percent of LR-CVC cases with CONS bacteremia lasting 1 or 2 days were treated successfully without CVC removal. The success rate decreased to 44% with a 3- to 4-day duration of bacteremia. None of 19 infants with CONS bacteremia lasting >4 days was treated successfully until CVCs were removed. CONCLUSIONS: Prolonged CONS bacteremia was avoided by early removal of CVCs. Retention of CVCs was successful in 46% of neonates with CONS bacteremia in whom it was attempted, but it was never successful if bacteremia lasted >4 days.

Bacteremia↗

Central venous catheter removal versus in situ treatment in neonates with enterobacteriaceae bacteremia.

OBJECTIVE: To determine how often neonates with Enterobacteriaceae (ENTB) bacteremia can be treated successfully without removing central venous catheters (CVCs). METHODS: A retrospective cohort study was conducted of ENTB bacteremia and CVCs in infants in a neonatal intensive care unit during a 7-year period (1994-2000). Cases of ENTB bacteremia were identified from a microbiology database and limited to late-onset cases occurring after 3 days of age. RESULTS: There were 53 cases of ENTB bacteremia in infants with CVCs. Blood cultures were positive for ENTB within a median of 10 hours (range: 5-43). Timing of CVC removal was at the discretion of attending neonatologists. Fifteen cases had early-removal CVC (ER-CVC) within 2 days, and 38 cases had late-removal CVC (LR-CVC) >2 days after the first positive blood culture for ENTB. There were no significant differences between infants in the ER-CVC and LR-CVC groups for case fatality, recurrence, or duration of ENTB bacteremia. Although 16 (42%) of 38 (95% confidence interval [CI]: 26%-59%) LR-CVC cases required CVC removal to resolve ENTB bacteremia, 17 (45%) of 38 (95% CI: 29%-62%) LR-CVC cases were treated successfully without removal of CVCs. ENTB bacteremia was successfully treated without CVC removal in 85% of 13 LR-CVC cases with 1 day of bacteremia in contrast to 24% of 25 LR-CVC cases with >1 day of bacteremia (relative risk: 3.5; 95% CI: 1.7-7.4). CVC removal was required to resolve ENTB bacteremia in 9 (82%) of 11 LR-CVC cases with severe thrombocytopenia compared with 7 (32%) of 22 LR-CVC cases without severe thrombocytopenia (relative risk: 2.6; 95% CI: 1.3-5.0). CONCLUSIONS: Retention of CVCs was successful in 45% of cases of ENTB bacteremia in which it was attempted, but success was unlikely when bacteremia lasted >1 day. ENTB bacteremia cases associated with severe thrombocytopenia rarely resolved unless CVCs were removed.

Aminoglycosides↗

Clinical characteristics and prognostic factors of patients with Stenotrophomonas maltophilia bacteremia.

Stenotrophomonas maltophilia is an important nosocomial pathogen with intrinsic multi-drug resistance. This retrospective study reviewed 84 episodes of S. maltophilia bacteremia over a 4-year period from July 1999 to September 2003. Stenotrophomonas maltophilia bacteremia was hospital-acquired in 64 patients (76%), and developed after prolonged hospitalization in 48 (57%). Seventy patients (83%) had a central venous catheter (CVC), 64 (76%) had prior antibiotic therapy, 55 (65%) had underlying malignancy, and 43 (51%) were receiving immunosuppressive therapy. Twenty seven percent of the episodes of bacteremia had polymicrobial isolates. The overall and bacteremia-related mortality rates were 44% and 33%, respectively. Forty six percent of the bacteremia-related mortality occurred within 3 days after onset of symptoms. The most common sources of bacteremia were respiratory tract (33%) and CVC (31%), while the source of the bacteremia was unknown in 26% of episodes. The most effective antibiotics in vitro were trimethoprim-sulfamethoxazole, ciprofloxacin, chloramphenicol, and ceftazidime; however, a trend of increasing drug resistance in these agents was identified over the study period. On univariate analysis, nosocomial bacteremia, long-lasting neutropnenia (>10 days), bacteremia originating from the respiratory tract, shock, low serum albumin level (<3 g/dL), and thrombocytopenia (platelet count <100,000/mm3) were significantly related to mortality (p<0.05). Among these variables, shock and thrombocytopenia were independent factors associated with mortality. In contrast, patients with CVC-related bacteremia had a lower mortality rate (odds ratio, 0.04; p<0.001). Patients treated with appropriate antibiotics had a lower mortality rate, but this difference was not significant (p=0.477). In S. maltophilia bacteremia, careful evaluation of CVC was important for identifying the source of bacteremia and predicting prognosis. The source of bacteremia and condition of patients at presentation were the major factors influencing prognosis.

Anti-Bacterial Agents↗

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae hospital acquired bacteremia. Risk factors and clinical outcome.

OBJECTIVE: To study the risk factors and clinical outcome in patients having extended-spectrum beta-lactamase producing (ESBL) Klebsiella pneumoniae (K. pneumoniae) hospital acquired bacteremia. METHODS: The study was conducted at 500 bedded King Fahad Hospital and Tertiary Care Center, Al-Hofuf, Al-Hasa, Eastern Province of Saudi Arabia. Retrospectively infection control and microbiology records of patients having hospital acquired K. pneumoniae bacteremia during July 2001 to July 2003 were reviewed. Data on age, gender, location, onset of bacteremia, hospital stay after onset of bacteremia, prior antibiotic therapy, comorbid conditions and clinical outcome were recorded. RESULTS: During 2 years of study period 26 patients developed hospital acquired K. pneumoniae bacteremia, out of them 10 patients had bacteremia due to ESBL producing strains. Extended-spectrum beta-lactamase producing K. pneumoniae bacteremia was significantly higher among patients of less than 65 years of age (p=0.004). Klebsiella pneumoniae bacteremia was more common (12/26, 46.1%) among diabetic patients and 8/12 had ESBL K. pneumoniae bacteremia. (p=0.02). Invasive devices (urinary and vascular catheters) were more commonly observed among patients having ESBL K.pneumoniae bacteremia (p=0.004, 0.001). Significantly higher number (9/10) of patients with ESBL K.pneumoniae bacteremia received prior third generation cephalosporins (p=0.001). Extended-spectrum beta-lactamase K. pneumoniae hospital acquired bacteremia had significantly longer hospital stay and higher mortality (p=0.0001). CONCLUSION: Elderly age, diabetes, invasive devices and prior third generation cephalosporin therapy are the major risk factors for hospital acquired ESBL K.pneumoniae bacteremia, leading to significantly higher mortality and prolonged hospitalization. Infection control measures should be aggressively followed to prevent such infections among these high risk patients.

Adolescent↗

Central venous catheter and Stenotrophomonas maltophilia bacteremia in cancer patients.

BACKGROUND: Stenotrophomonas maltophilia bacteremia is frequently found in cancer patients. This study attempted to determine how often the catheters were the source of this infection and the risk factors associated with catheter-related bacteremias. METHODS: The microbiology records were retrospectively reviewed of all cancer patients having S. maltophilia bacteremia and indwelling central venous catheters seen between January 1998 and January 2004. In a multivariate analysis the patients' clinical characteristics, antimicrobial therapy, outcome, and source of bacteremia that were significantly associated with definite catheter-related S. maltophilia bacteremia as opposed to secondary bacteremia were identified. RESULTS: A total of 217 bacteremias were identified in 207 patients: 159 (73%) were primary catheter-related (53 definite, 89 probable, and 17 possible), 11 (5%) were primary noncatheter-related, and 47 (22%) were secondary. Multivariate analysis showed the following factors to be independently associated with definite catheter-related bacteremias: 1) polymicrobial bacteremia (odds ratio [OR], 7.6; 95% confidence interval [95% CI], 1.3-45.5); 2) no prior intensive care unit admission (OR, 0.06; 95% CI, 0.005-0.578); and 3) nonneutropenic status at onset (OR, 0.07; 95% CI, 0.013-0.419). The response rate to appropriate antibiotics and catheter removal was 95% in the patients with definite catheter-related bloodstream infections, compared with only 56% in the patients with secondary bacteremias (P = .001). CONCLUSIONS: The majority of the S. maltophilia bacteremias occurring in cancer patients with indwelling central venous catheters appear to be catheter-related and are often polymicrobial. Catheter-related S. maltophilia bacteremias occurred more frequently in noncritically ill, nonneutropenic patients, and prompt removal of the catheter was found to be associated with a better prognosis.

Adult↗

Is presentation of bacteremia in the elderly the same as in younger patients?

OBJECTIVE: To compare the presentation of bacteremia in young and elderly patients. PATIENTS AND METHODS: Seventy-one elderly (mean age 80.4 years) and 34 younger inpatients (mean age 45.7 years) with bacteremia were prospectively studied. These were compared with a control group of 187 geriatric patients (mean age 81.3 years) with clinical signs of bacteremia but in whom blood cultures were negative. Bacteremia was defined as one or more positive blood cultures showing a pathogenic bacteria in patients with clinical signs of bacteremia. In all 105 patients with bacteremia, 16 common clinical or biological signs of the disease were immediately investigated after blood culture. Patients were classified into three groups: elder patients and young patients with bacteremia and elderly patients without bacteremia. RESULTS: Only three clinical findings of the 16 studied were found in at least 70% of the bacteremic elderly patients: fever, increased erythrocyte sedimentation rate, and a clinical indication of the source of infection. These three signs were found statistically more often in bacteremic elderly compared with nonbacteremic elderly patients (P < 0.01). Seven other signs (hypothermia, altered mental state, leukopenia, and lymphopenia) had a specificity above 80%. On a logistic regression analysis, four variables were significantly and independently associated with bacteremia in the elderly: rapid onset of infection (defined as a period < or = 48 hours between the earliest manifestation of bacteremia and the time of blood blood sample), fever, altered general state, and clinical indication of the source of infection. Younger infected patients had more chills, sweating, alter general state, altered mental state or lymphopenia than did the bacteremic elderly patients. Bacteremic elderly patients had statistically few symptoms than the young infected patients (P < 0.001). CONCLUSIONS: In elderly patients with early stage bacteremia, most of the signs or symptoms that are considered typical in the literature appear irregularly. None appeared pathognomonic. Elderly patients with bacteremia had fewer signs or symptoms than younger infected patients.

Aged↗

Nosocomial and community-acquired Staphylococcus aureus bacteremias from 1980 to 1993: impact of intravascular devices and methicillin resistance.

The rate of nosocomial bacteremia due to Staphylococcus aureus has increased over the past decade, but trends in community-acquired S. aureus bacteremia are less certain. This hospital-based observational study compares nosocomial and community-acquired S. aureus bacteremias during 1980-1983 and 1990-1993. The rate of nosocomial S. aureus bacteremia increased from 0.75 to 2.80 cases per 1,000 discharges, while the rate of community-acquired S. aureus bacteremia increased from 0.84 to 2.43 cases per 1,000 discharges. The number of nosocomial device-related bacteremias increased eightfold; 56% of S. aureus bacteremias were associated with devices during 1990-1993. Intravascular devices were associated with no community-acquired S. aureus bacteremias during 1980-1983 but with 22% during 1990-1993. Methicillin-resistant S. aureus (MRSA) seldom caused bacteremia during 1980-1983. From 1990 to 1993, MRSA caused 32% and 18.5% of nosocomial and community-acquired S. aureus bacteremias, respectively. The rates of both community-acquired and nosocomial S. aureus bacteremias have increased significantly since 1980. In addition to their role in nosocomial infections, MRSA and intravascular device-related S. aureus bacteremias are emerging problems in the nonhospital setting.

Bacteremia↗

Streptococcus pneumoniae bacteremia in children infected with HIV: presentation, course, and outcome.

OBJECTIVE: To examine the presentation, course, and outcome of pneumococcal bacteremia in children infected with human immunodeficiency virus (HIV). METHODS: A retrospective series of HIV-infected children less than 18 years of age with Streptococcus pneumoniae bacteremia from four urban, tertiary care hospitals was evaluated. The main outcome measures included persistent bacteremia, the development of a focal infection, and death. RESULTS: Seventy-two episodes of pneumococcal bacteremia were identified in 59 patients. Fifty-four first episodes were included; 26/54 were occult. Mean temperature was 39.8 degrees C. In patients with bacteremia, white blood cells (WBCs) > or = 15,000 and > or = 10,000 had sensitivities of 40% and 75%, respectively. At the time of bacteremia, age >3 years old was associated with a lower mean WBC count compared with episodes occurring in patients <3 years old (11.2 vs 16.1, P < 0.05). Patients with occult bacteremia who were discharged with antibiotics (12 i.m., 7 p.o.) were less likely than patients without antibiotic treatment to have persistent bacteremia at a return visit within 72 hours (0/19 vs 2/5, P < 0.05). No patient with occult bacteremia died, progressed to clinical meningitis, or had other sequelae. Two of fifty-four patients died as a result of their first episode of invasive pneumococcal disease. Both patients who died had meningitis and appeared ill on initial presentation. CONCLUSIONS: Neither a WBC count > or = 15,000 nor > or = 10,000 is a sensitive indicator of pneumococcal bacteremia in HIV-infected children. Empiric antibiotics are useful to decrease the risk of persistent bacteremia. Children infected with HIV who have occult pneumococcal bacteremia appear to do well with appropriate antibiotics. Patients who are afebrile and well appearing on reevaluation may be safely treated as outpatients.

AIDS-Related Opportunistic Infections↗

Comparison of lysis filtration and an automated blood culture system (BACTEC) for detection, quantification, and identification of odontogenic bacteremia in children.

Lysis filtration (LyF) was compared with BACTEC PAEDS PLUS in estimating the prevalence of, and sensitivity for, detection of odontogenic bacteremia. Both real bacteremia and simulated bacteremia (seeded blood or saline samples) were assessed to determine the validity of LyF in estimating bacteremia. The simulated bacteremia was also used to assess the reliability of LyF to estimate intensity of bacteremia in CFU per milliliter of blood. Reference organisms were used to assess the abilities of LyF and BACTEC to isolate known oral streptococci. There was no difference in the number of CFU per milliliter of seeded saline, seeded blood, and drop cultures of the organisms plated directly onto agar. Blood cell volume had a negligible effect on the yield of organisms for simulated bacteremia. When LyF and BACTEC were compared, the time to detection of bacteremia was always significantly shorter for BACTEC. For aerobic cultures, these times were 43.7 and 9.6 h, respectively (P < 0.01). For anaerobic cultures, these times were 45.1 and 9.9 h, respectively (P < 0.01). These differences occurred as well for bacteremia following the extraction of a single tooth, with LyF and BACTEC aerobic cultures taking 78 and 30.5 h, respectively (P < 0.0001). For anaerobic cultures, the times were 90.8 and 45 h, respectively (P < 0.0004). A preextraction bacteremia was detected on 2.1% of occasions with BACTEC compared to 31% of occasions with LyF (P < 0.05) The use of LyF was an effective and reliable means of estimating the intensity of pre- and postextraction bacteremia. The values were 3.6 and 5.9 CFU/ml, respectively (P < 0.4729), and the difference was not statistically significant. In summary, BACTEC is quicker than LyF, but less sensitive. LyF provides additional important information in estimating the intensity of bacteremia.

Adolescent↗

Occult bacteremia with group B streptococci in an outpatient setting.

OBJECTIVES: We undertook this study to determine the relative frequency of occult bacteremia with group B streptococci (GBS) and to define the clinical features of infants with occult bacteremia attributable to GBS at the time of initial clinical contact. DESIGN: The logs of the microbiology laboratory were reviewed for blood and cerebrospinal fluid isolates of GBS from 1982 to 1996. Records of patients identified with GBS were abstracted. Patients were classified as having occult bacteremia if GBS were isolated from their blood and they seemed nontoxic and had no apparent clinical or laboratory evidence of focal infection. All other patients were diagnosed with sepsis, meningitis, or nonmeningeal foci. RESULTS: We reviewed the medical records of 147 children with GBS and identified 108 outpatients, including 47 (44%) with occult bacteremia, 42 (39%) with meningitis, 11 (10%) with nonmeningeal foci, and 8 (7%) with sepsis. Compared with patients with sepsis or focal infections, those with occult bacteremia were older (61.1 vs 39.1 days) and had slightly, although not significantly, higher white blood cell (WBC) counts (13 280 +/- 6854 vs 10 688 +/- 8574), but similar degrees of fever. Among the 47 patients with occult bacteremia, none died, as compared with 2 of 61 with serious infections, and fewer had neurologic sequelae (0/47 vs 11/61). Patients with occult bacteremia >90 days of age generally had temperatures >39 degreesC (9/11, mean 39.3 degreesC) and WBC counts >15 000/mm3 (7/10, mean 19 070/mm3), both of which differed significantly compared with those who were <90 days of age. Thirty of the 47 patients with occult bacteremia received intravenous antibiotics and recovered. One of 8 patients discharged without antibiotics and none of 8 with antibiotics developed a focal complication; 1 discharged patient was lost to follow-up. CONCLUSIONS: Almost one-half of the children with GBS disease beyond the immediate neonatal period had occult bacteremia. Among 8 untreated patients with bacteremia, 1 developed a focal complication. Although the small proportion of children with GBS occult bacteremia who were >90 days of age usually had the risk factors of temperature >39 degrees C and WBC >15 000/mm3, as seen with occult bacteremia attributable to other organisms, the majority of the patients who were younger did not have a characteristic clinical syndrome. Prevention of sequelae in these young infants will require a low threshold for diagnosis and treatment.

Ambulatory Care↗

[Epidemiology of hospital bacteremias in eastern France. Eastern CCLIN Network].

Bacteremia occurs frequently among critically ill patients. The aim of this study carried out in Eastern France was to describe the epidemiology of nosocomial bacteremia and to assess the methicillin-resistance of Staphylococcus aureus (SA). Data were collected during a 4 months prospective survey (09/96-12/96) carried out among 44 hospitals. We counted 2633 episodes of bacteremia classified as contamination (684), nosocomial bacteremia (970) and community bacteremia (979). Incidence rate of nosocomial bacteremia was 30.7 per 100 beds in the intensive care units. When documented, the origin of the nosocomial bacteremia was the most often catheter blood related infection or urinary tract infection. Gram positif cocci were predominant among nosocomial bacteremia (53.8%). Among Gram negative bacteria (enterobacteria) (31.6%), Escherichia coli was the most frequently isolated. SA was methicillin-resistant in 18.3% of community bacteremia and in 26.5% of nosocomial bacteremia. Coagulase negative Staphylococcus were methicillin-resistant in 25.4% of community bacteremia and in 60.1% of nosocomial bacteremia. Measures to prevent catheter blood related infections and urinary tract infections may be started.

Bacteremia↗

Nosocomial bacteremia. An epidemiologic overview.

Each year nosocomial bacteremia develops in approximately 194,000 patients in U.S. hospitals (5/1,000); 75,000 die. These infections portend $.28 to $.86 billion added costs to health care. Most nosocomial bacteremias occur endemically and are secondary bacteremias, caused by postoperative wound or intra-abdominal infections, urinary tract infections or pneumonia; primary bacteremias most frequently originate from intravascular devices, but the source is unrecognized. Between 1965 and 1978, 97 epidemics of nosocomial bacteremia, including 11 of "pseudobacteremia," were reported. In contrast to endemic bacteremias, 78 percent of the epidemics involved primary bacteremias: 33 outbreaks stemmed from infusion therapy in some form, including seven epidemics traced to a contaminated commercial product. Two thirds of endemic nosocomial bacteremias and 79 percent of epidemics are caused by aerobic gram-negative bacilli. Pseudomonas cepacia, Pseudomonas maltophilia, Flavobacterium and Enterobacter agglomerans rarely cause endemic bacteremia and when encountered often signal an epidemic. Whereas predisposing host conditions greatly increase the risk of bacteremia endemically nosocomial epidemics occur mainly in immunocompetent patients and are related to what therapeutic measures have been taken: segregation in a special care unit (58 percent of outbreaks) or exposure to infusion therapy or other invasive procedures involving the bloodstream (65 percent). At present only about one fourth of endemic nosocomial bacteremias are in theory preventable by more consistent application of existent knowledge of asepsis. The potential for prevention seems greatest for epidemic bacteremias, most of which are related to exposure to invasive devices, to a common source of contamination, or both.

Blood Pressure Determination↗

Pathophysiology of bacteremia.

Despite the frequency and importance of both nosocomial and "community-acquired" bacteremia, definitive information concerning crucial pathophysiologic events in human bacteremia remains sparse. An extensive variety of clinical manifestations, such as fever, rigors, shock, altered circulatory dynamics, cutaneous manifestations changes in the coagulation, complement, and other mediator systems, and effects on the lungs, heart, kidney, liver, and other end organs, have been described, but it is difficult to determine the relative frequency of these events in bacteremia caused by different species. The extensive number of bacterial species capable of producing bacteremia and variations in the type of presentation, such as acute, asymptomatic, and chronic, even when bacteremia is produced by the same species, undoubtedly contribute to this difficulty and suggest that a variety of pathophysiologic mechanisms occur in various bacteremias. In contrast, the relative frequency of various manifestations and some pathophysiologic mechanisms have been better delineated in Gram-negative bacteremia. The development of bacteremia enhances the lethality of most types of localized infection and several studies have demonstrated a relation between the magnitude of bacteremia and the outcome of the disease. Among various pathophysiologic alterations, mechanisms involved in the production of fever have been delineated most clearly. Fever appears to reflect a "common pathway" with almost all infectious agents and results from release of endogenous pyrogen from phagocytic cells. Endogenous pyrogen regulates the thermostatic setting of the body through its effect on the anterior hypothalamus. Endogenous pyrogen seems identical with Interleukin 1 and exerts a variety of other biologic activities. An extensive number of bacterial components have been proposed as "effectors" and an equally large number of endogenous substances proposed as "mediators" of the pathophysiologic events in bacteremia. The importance of many of these effectors and mediators has been postulated largely on the basis of in vitro and animal studies. The lack of critical clinical studies hampers extrapolation of these experimental studies to human bacteremia. The development of more effective therapy for the complications of bacteremia, such as shock, will continue to be hampered until the mechanisms involved in the production of those pathophysiologic events that are crucial determinants of outcome have been delineated more precisely in human disease.

Bacterial Toxins↗

Recurrent gram-negative bacteremia.

PURPOSE: Recurrent gram-negative bacteremia is defined as two or more episodes of bacteremia occurring in the same patient with an infection-free interval between each episode. Our purpose was to identify patients with recurrent gram-negative bacteremia in order to define possible risk factors for its recurrence. PATIENTS AND METHODS: During a recently completed prospective study of all episodes of gram-negative bacteremia at the Buffalo Veterans Administration Center between April 1, 1984, and May 31, 1987, 35 patients with 74 episodes of gram-negative bacteremia were identified. The following information was obtained from all 35 patients: age, service, date of hospital admission, date of the bacteremia, underlying diseases, initial antimicrobial therapy, focus of infection, the presence or absence of shock, antimicrobial susceptibility of the blood isolate, and outcome. RESULTS: All 35 patients were men, had a mean age of 69 years, and all had one or more underlying diseases; 45 percent had a malignancy. The duration of time between a pair of episodes was four weeks or more for 74 percent of 38 pairs of episodes. In 25 of 38 (66 percent) pairs of episodes, the focus of infection was the same; in 80 percent of these 25 pairs, the urinary tract was the focus. Overall, the urinary tract was the focus of gram-negative bacteremia in almost 50 percent. Escherichia coli was the single most common organism isolated (28 percent of all episodes), followed by Proteus mirabilis (17.5 percent) and Pseudomonas aeruginosa (17.5 percent). Six of 35 (17 percent) patients died due to gram-negative bacteremia; five of these six had a respiratory tract focus of infection. CONCLUSIONS: In a population of veterans, recurrent gram-negative bacteremia was identified in almost 10 percent of all patients with gram-negative bacteremia during a 37-month study period. Recurrent gram-negative bacteremia most frequently occurred in the setting of underlying malignancy with the urinary tract as a common focus of infection. The mortality rate of 17 percent was similar to that of all patients with gram-negative bacteremia reported in previous studies.

Aged↗

Platelet-activating factor and bacteremia-induced pulmonary hypertension.

BACKGROUND: Acute lung injury is a common complication of gram-negative sepsis. Pulmonary hypertension and increased lung vascular permeability are central features of lung injury following experimental bacteremia. Platelet-activating factor is a prominent proinflammatory mediator during bacterial sepsis. Our previous studies have demonstrated that exogenous administration of platelet-activating factor (PAF) induces pulmonary edema without causing pulmonary hypertension. Interestingly, inhibition of PAF activity during Escherichia coli bacteremia prevents the development of both pulmonary hypertension and pulmonary edema. These data suggest that PAF contributes to pulmonary hypertension during sepsis, but that this is unlikely to be a direct vascular effect of PAF. The goal of the present study was to investigate the mechanism by which acute E. coli bacteremia induces pulmonary injury and to define the role that PAF plays in this injury. We hypothesized that the effects of PAF on pulmonary hypertension during bacteremia are due to the effects of PAF on other vascular mediators. Several studies suggest that PAF induces the expression of endothelin-1 (ET), a potent peptide vasoconstrictor. Further, our previous studies have implicated ET as a central mediator of systemic vasoconstriction during bacteremia. We therefore sought to assess whether ET is modulated by PAF. E. coli has also been demonstrated to increase endothelial production of nitric oxide (NO), which contributes to maintenance of basal vascular tone in the pulmonary circulation. We hypothesized that PAF might increase pulmonary vascular resistance during bacteremia by activating neutrophils, increasing expression of ET, and decreasing the tonic release of NO. Furthermore, we hypothesized that hypoxic vasoconstriction did not contribute to pulmonary vasoconstriction during the first 120 min of E. coli bacteremia. METHODS: Pulmonary artery pressure (PAP), blood pressure (BP), heart rate (HR), and arterial blood gases (ABG) were measured in anesthetized spontaneously breathing adult male Sprague-Dawley rats. E. coli (10(9) CFU/100 g body wt) was injected at t = 0, and hemodynamic data were obtained at 10-min intervals and ABG data at 30-min intervals for a total of 120 min. Sham animals were treated equally but received normal saline in place of E. coli. In treatment groups, a 2.5 mg/kg dose of WEB 2086, a PAF receptor antagonist, was administered intravenously 15 min prior to the onset of sepsis or sham sepsis. The groups were (1) intravenous E. coli (n = 5); (2) intravenous WEB 2086 pretreatment + intravenous E. coli (n = 5); (3) intravenous WEB 2086 alone (n = 5); and (4) intravenous normal saline (n = 6). Nitric oxide metabolites (NOx) and ET concentrations were assayed from arterial serum samples obtained at the end of the protocol. Lung tissue was harvested for measurement of myeloperoxidase (MPO) activity and pulmonary histology. RESULTS: E. coli bacteremia increased HR, PAP, and respiratory rate early during sepsis (within 20 min), while hypoxemia, hypotension, and hemoconcentration were not manifest until the second hour. Pretreatment with WEB 2086 completely abrogated all of these changes. E. coli bacteremia increased the activity of serum ET, lung MPO, and neutrophil sequestration in the lung parenchyma via a PAF-dependent mechanism. However, the mechanism of increased production of NO appears to be PAF independent. CONCLUSIONS: These data support the hypothesis that E. coli bacteremia rapidly induces pulmonary hypertension stimulated by PAF and mediated at least in part by endothelin-1 and neutrophil activation and sequestration in the lung. Microvascular injury with leak is also mediated by PAF during E. coli bacteremia, but the time course of resultant hypoxemia and hemoconcentration is slower than that of pulmonary hypertension. The contribution of hypoxic vasoconstriction in exacerbating pulmonary hypertension in gram-negative sepsis is probably a late

Animals↗

Bacteremia in adult patients with acquired immunodeficiency syndrome in the northeast of Thailand.

BACKGROUND: Bacteremia is a frequent complication found in HIV-infected patients and is usually associated with a poor prognosis. This study was undertaken to describe the bacterial pathogens causing bacteremia in adult Thai HIV-infected patients, and hence to give guidance in the choice of empirical antimicrobials. METHODS: Blood culture results at Srinagarind Hospital, Khon Kaen during the period January 1996 to December 2001 were retrospectively reviewed. RESULTS: In HIV-infected and HIV-uninfected patients, 172 and 4082 episodes of bacteremia occurred, respectively. In HIV-infected patients, community-acquired and nosocomial bacteremia were found in 78.5% and 21.5%, respectively and most were monomicrobial. Gram-negative bacteria were the main pathogens isolated in both groups of bacteremia. Escherichia coli and methicillin-resistant Staphylococcus aureus were more common pathogens causing nosocomial bacteremia in HIV-infected patients, whereas Acinetobacter spp were more common in HIV-uninfected patients. Salmonella spp, especially Salmonella groups D and B, were the most common (62.2%) pathogen in community-acquired bacteremia in HIV-infected patients whereas Escherichia coli was the most common in HIV-uninfected patients. Only a few episodes of community-acquired bacteremia in HIV-infected patients had identified sources. Co-trimoxazole resistance was common in community-acquired bacteremia caused by Gram-negative bacilli in HIV-infected patients, with Salmonella group B being more resistant to co-trimoxazole than Salmonella group D (statistically significant, p<0.001). However, resistance rates to ceftriaxone and ofloxacin were low. CONCLUSIONS: Bacteremia in adult HIV-infected patients was usually caused by Gram-negative bacilli in both community-acquired and nosocomial settings. Salmonella spp was the most common organism identified, especially Salmonella group B and D. Ceftriaxone or fluoroquinolones such as ofloxacin or ciprofloxacin should be used as the initial empiric therapy for HIV-infected patients with suspected bacteremia.

Acquired Immunodeficiency Syndrome↗