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Bacteremia after diagnostic conventional laparoscopy and minilaparoscopy: a prospective study in 100 patients.

BACKGROUND/GOALS: Diagnostic laparoscopy under sedoanalgesia is a valuable tool in the work-up of liver diseases and is helpful as a staging procedure. The rate of bacteremia caused by this procedure is unknown, in particular when performed as minilaparoscopy. STUDY: A 100 consecutive patients having undergone diagnostic laparoscopy carried out either conventionally (group I, n=50) or as minilaparoscopy (group II, n=50) were prospectively enrolled in this study. Blood cultures were drawn before and within 5 minutes after the procedure. Risk factors for bacteremia were evaluated. RESULTS: Bacterial growth occurred in 4 blood cultures drawn immediately after laparoscopy. No patient developed fever or other signs of infection in the follow-up. Risk factors predisposing to bacteremia could not be identified. CONCLUSIONS: Conventional diagnostic laparoscopy under sedoanalgesia and minilaparoscopy are associated with a low rate of bacteremia as in diagnostic upper endoscopy.

Adult↗

Nitric oxide mediates redistribution of intrarenal blood flow during bacteremia.

The normal or hyperdynamic circulatory response during the early phases of the systemic septic response is associated with renal microvascular constriction and can result in renal dysfunction. Intrarenal redistribution of blood flow from the outer cortex to the medulla appears to account for decreased glomerular filtration in spite of normal or elevated renal blood flow, but the mechanisms of this response are not well described. Nitric oxide is recognized as an important regulator of regional blood flow during both normal and pathologic conditions including sepsis, and we hypothesized that alterations in nitric oxide contribute to redistribution of renal blood flow during sepsis. The current study used laser Doppler fluximetry and clearance of p-aminohippuric acid (effective renal plasma flow, ERPF) to study intrarenal distribution of blood flow during basal conditions and during normodynamic Escherichia coli bacteremia, with and without inhibition of nitric oxide. Inhibition of nitric oxide in normal animals resulted in a decrease in ERPF (-19%) with a decrease in cortical flux (-39%) without alteration of medullary flux. Bacteremia resulted in a decrease in cortical flow (-17%), an increase in medullary flow (36%), and a modest reduction (-9%) in ERPF. Inhibition of nitric oxide synthase during bacteremia worsened cortical flow (-43%), reversed the increase in medullary flux (-42%), and further impaired ERPF (-28%). These data suggest that nitric oxide regulates renovascular tone during normal conditions and bacteremia, and indicate that it is a prime mediator of intrarenal redistribution of blood flow during sepsis.

Animals↗

Group A streptococcal bacteremia. A 10-year prospective study.

In this paper we present a prospective evaluation of 100 patients with Group A Streptococcal (GAS) bacteremia evaluated in our hospital over a 10-year period. Sixty-two patients were intravenous drug users (IVDU); all but 1 of these had an obvious cutaneous portal of entry related to the injection of illicit drugs. Twenty-seven patients had infectious metastasis, and the presence of septic pulmonary embolism was associated with suppurative phlebitis. Four of these patients had endocarditis. In the non-IVDU group, 24 patients had an underlying disease, and 12 were immunosuppressed. In 14 cases the infection was of hospital acquisition; in 35% infection was related to medical manipulations. Comparing the IVDU and non-IVDU groups, GAS bacteremia in IVDU patients is associated with a more benign outcome, a longer time of evolution before diagnosis, and a lower frequency of septic shock and mortality than in non-IVDU patients. Although in the univariate analysis GAS bacteremia was associated with several variables, in the multivariate analysis only the presence of shock and nosocomial acquisition of the infection were independently associated with a fatal outcome. Fifty-two patients were infected with human immunodeficiency virus (HIV); 5 of these were in the non-IVDU group. During the last 5 years of study, GAS bacteremia in our hospital was 39 times more frequent in HIV-infected patients than in patients without HIV. Nine patients presented clinical criteria corresponding to Streptococcal toxic shock syndrome (STSS), although its incidence was lower in the IVDU group. In the non-IVDU group, STSS was more frequent in patients with a necrotizing portal of entry, an age between 20 and 40 years, women, and when the origin of the infection was the skin or soft tissue. Six patients with STSS died, and death was associated with the presence of necrotizing lesions and lower counts of white cells, platelets, or hemoglobin.

Adolescent↗

Selective use of vancomycin to prevent coagulase-negative staphylococcal nosocomial bacteremia in high risk very low birth weight infants.

OBJECTIVE: To determine whether vancomycin added to parental nutrition (PN) fluids could prevent nosocomial infections in very low birth weight newborns and which infants would benefit most from prophylaxis. DESIGN: Double blind, randomized controlled study. SETTING AND STUDY POPULATION: Very low birth weight infants receiving PN in a tertiary neonatal intensive care unit. METHODS: Thirty-eight infants with and without central vascular catheters were randomized to receive no medication or 25 microg/ml vancomycin added to PN for the duration of the infant's PN requirements. RESULTS: The addition of 25 microg/ml vancomycin to PN prevented bacteremia in very low birth weight infants receiving PN. There was a significant reduction in the number of coagulase-negative staphylococcal (CONS) bacteremias (defined as isolation of the same organism from two positive blood cultures) during PN (5 vs. 0; P = 0.037) as well as the total number of bacteremias and fungemias (9 vs. 1; P = 0.036). The total number of hospital days (108 +/- 13 vs. 76 +/- 6; P = 0.039) were reduced in infants receiving vancomycin. Infants with birth weights of < 1000 g who received corticosteroids for treatment of chronic lung disease benefitted most from treatment. No vancomycin-resistant strains of CONS or enterococci were detected during the study period. CONCLUSIONS: Prophylactic treatment with vancomycin effectively prevented CONS bacteremia under the conditions of the study. Its use was most effective in infants with birth weights of <1000 g.

Anti-Bacterial Agents↗

Clinical implications of penicillin and ceftriaxone resistance among children with pneumococcal bacteremia.

OBJECTIVES: To determine whether reduced penicillin or ceftriaxone susceptibility affects clinical presentation and outcome in children with pneumococcal bacteremia. DESIGN: Retrospective review of patients with Streptococcus pneumoniae bacteremia. RESULTS: We reviewed 922 cases of pneumococcal bacteremia. Of 744 isolates with known penicillin (PCN) susceptibilities 56 were PCN-nonsusceptible. The majority displayed intermediate resistance; 14 of 730 isolates with known ceftriaxone (CTX) susceptibilities were CTX-nonsusceptible. Neither the PCN- nor the CTX-nonsusceptible cohort displayed a difference from its susceptible counterpart in temperature, respiratory rate or white blood cell count on initial patient evaluation, although trend suggested they were more often admitted at the initial visit. At follow-up only children treated initially with antibiotic were evaluated. Children with PCN-nonsusceptible isolates were no more likely to be febrile than those with PCN-susceptible isolates (28% vs. 25%, P = 0.61) and were no more likely to have a positive repeat blood culture (0% vs. 1%, P = 0.59) or a new focal infection (10% vs. 6%, P = 0.79). Data concerning CTX-nonsusceptible organisms were limited by the low number of such isolates. Although patients with CTX-nonsusceptible pneumococci were more likely to be febrile at follow-up than those with CTX-susceptible organisms (67% vs. 24%, P = 0.04), we were unable to demonstrate a significant difference for other endpoints. CONCLUSIONS: Reduced antibiotic susceptibility does not alter the clinical presentation of pneumococcal bacteremia. With current practice intermediate resistance to PCN is of little clinical significance in nonmeningitic systemic pneumococcal infections.

Adolescent↗

Gram-negative bacillary bacteremia in human immunodeficiency virus type 1-infected children.

BACKGROUND: HIV-infected children are particularly susceptible to serious bacterial infections including Gram-negative bacillary bacteremia (GNB). However, the information available on GNB in these children is limited. METHODS: Retrospective review of hospital charts of HIV-infected children with GNB diagnosed between 1980 and 1997. The association between bacteremic episodes, degree of immunosuppression, HIV severity, medical treatment and clinical outcome was assessed. RESULTS: Of 680 HIV-infected children, 72 (10.6%) had 95 episodes of GNB. Statistical analyses were restricted to data from the first episode. The mean age (+/-SD) at diagnosis of GNB was 2.5 +/- 2.7 years (median, 1.6). The predominant organisms were Pseudomonas aeruginosa (26.4%), nontyphoidal Salmonella (15.3%), Escherichia coli (15.3%) and Haemophilus influenzae (12.5%). The relative frequency, per 5-year interval, of P. aeruginosa bacteremia steadily increased from 13% during 1980 through 1984 to 56% during 1995 through 1997. There were no cases of H. influenzae bacteremia after January 1, 1990. Eighty percent of GNB developed in children with AIDS and 72.2% developed in those with severe immunosuppression. Hypogamma-globulinemia and neutropenia were present in only 4.9 and 10.4% of first episodes, respectively. The overall case-fatality rate of GNB was 43.0%, and in children younger than 12 months it was 54.2%. CONCLUSIONS: A diagnosis of AIDS and/or severe immunosuppression was associated with increased risk of GNB, especially among younger children. Because of the high mortality of GNB, a broad spectrum antimicrobial therapy that effectively covers these organisms should be promptly instituted when bacteremia is suspected in HIV-infected children.

Bacteremia↗

Does recent vaccination increase the risk of occult bacteremia?

Several studies have questioned whether vaccination, especially against pertussis, increases the risk of invasive bacterial disease in young children in the immediate postvaccination period. In most cases, the antecedent of invasive bacterial disease is occult bacteremia. Therefore, we conducted a case-control study of children seen in an emergency department to determine whether there was an increased risk of occult bacteremia associated with recent vaccination. The case patients were obtained from an ongoing multicenter study of antibiotics for the management of suspected occult bacteremia; two age-matched controls were chosen for each case patient, consisting of one series of febrile nonbacteremic children and a second series of nonfebrile children with noninfectious complaints. The intervals from most recent vaccination to emergency department presentation were compared among case and control patients using the two-tailed t test. There was no significant difference in the time since last vaccination with any antigen, or with diphtheria-tetanus-pertussis in particular, among the case patients and patients in either control series. Recent vaccination was not associated with increased susceptibility to occult bacteremia among these children.

Bacteremia↗

Streptococcus pneumoniae bacteremia in patients with cancer: disease characteristics and outcomes in the era of escalating drug resistance (1998-2002).

In the current era of multidrug-resistant organisms, the clinical spectrum of Streptococcus pneumoniae infection remains unclear, especially in immunosuppressed patients with cancer. We sought to define the characteristics of pneumococcal bacteremia in patients who were receiving care at a comprehensive cancer center. All consecutive episodes of S. pneumoniae bacteremia between January 1998 and December 2002 were evaluated retrospectively. One hundred thirty-five episodes of pneumococcal bacteremia occurred in 122 patients. Sixty-three (52%) of 122 patients had hematologic malignancies; the others had solid tumors. The median Acute Physiology and Chronic Health Evaluation II score was 14 +/- 5. Twenty-four episodes (18%) occurred during neutropenia (<500 cells/microL). Sixty-five patients (53%) were receiving antineoplastic therapy, and 36 (30%) were receiving systemic corticosteroids. Twelve (41%) of 29 hematopoietic stem cell transplant (HSCT) recipients had received transplantation within 12 months of the infection diagnosis; 11 patients had graft-versus-host disease (chronic in 10). In 27 episodes (22%), S. pneumoniae bacteremia was considered as a breakthrough infection. Nine (56%) of 16 hospital-acquired episodes of S. pneumoniae bloodstream infection occurred in patients with profound neutropenia, whereas 15 (13%) of 119 episodes of community-acquired infection occurred during neutropenia (p < 0.0002). In 91 episodes (67%), patients had radiographic evidence of pneumonia. Infected catheters were associated with 21 episodes (16%). Forty-eight (36%) of 135 isolates were not susceptible to penicillin (minimum inhibitory concentration [MIC] > or = 2 microg/mL); 9 (7%) showed intermediate susceptibility to ceftriaxone (MIC >0.5 and <2.0 microg/mL). Nineteen patients (16%) died within 2 weeks of diagnosis; 18 deaths were attributed to systemic pneumococcal infection. Univariate analysis showed no significant increase in the risk of short-term death in patients with infection due to penicillin non-susceptible organisms (OR [odds ratio], 1.47; 95% confidence intervals [CI], 0.53-4.05; p < 0.46), initially discordant treatment (OR, 1.0; 95% CI, 0.62-665.4; p < 0.16), presence of pneumonia (OR, 1.19; 95% CI, 0.39-3.62; p < 0.76), neutropenia (OR, 1.0; 95% CI, 0.28-4.09; p < 0.92), systemic corticosteroid use (OR, 1.96; 95% CI, 0.69-5.60; p < 0.21), or antineoplastic therapy (OR, 1.45; 95% CI, 1.52-4.05; p < 0.47). Similarly, patients with hematologic cancers compared to those with solid cancers (OR, 1.0; 95% CI, 0.49-3.70; p < 0.56) and recipients of HSCT compared to those with no history of transplantation (OR, 1.0; 95% CI 0.59-12.71; p < 0.20) did not have a less favorable outcome. In conclusion, most pneumococcal bloodstream infections were community acquired, although hospital-acquired infections were common in neutropenic patients. It is noteworthy that initially discordant therapy, penicillin non-susceptible S. pneumoniae, and other conventional predictors of unfavorable outcome were not associated with increased mortality rates in these high-risk patients with cancer.

Adult↗

Lipopolysaccharide O-antigen promotes persistent murine bacteremia.

Bacteremia is a common complication of pneumonia with Klebsiella pneumoniae. In the previous work, we have shown that the lipopolysaccharide (LPS) O-antigen in K. pneumoniae O1:K2 contributes to lethality during pneumonia in part by promoting bacteremia. In the current work, we studied an O-antigen-deficient K. pneumoniae strain to further evaluate this polysaccharide's role in bloodstream infection. Cultured macrophage and murine bacteremia models were studied. In vitro, O-antigen-deficient bacteria, compared with wild-type organisms, were stronger activators of the murine alveolar macrophage cell line MH-S as assessed by nuclear localization of RelA/p65 and by secretion of cytokines and chemokines. O-antigen-deficient Klebsiellae were also more susceptible to killing by murine neutrophils. In vivo, the absence of O-antigen allowed more rapid and complete clearance of bacteria from the bloodstream, liver, and spleen after intravenous injection in mice. Survival was also greater among animals infected with bacteria missing the O-antigen. Gene expression profiling (via reverse transcriptase-polymerase chain reaction of 84 inflammatory mediator complementary DNA) revealed that by 24 h postinfection, the livers and spleens of animals infected with O-antigen-deficient organisms had significantly downregulated cytokine and chemokine expression compared with wild-type infected animals. The O-antigen surface carbohydrate of O1:K2 serotype K. pneumoniae appears to contribute to bacterial virulence by lessening the activation of macrophages, conveying resistance to killing by neutrophils, and by promoting persistent infection in the blood, liver, and spleen after the onset of bacteremia.

Animals↗

The use of antibiotics to prevent serious sequelae in children at risk for occult bacteremia: a meta-analysis.

OBJECTIVE: To determine whether antibiotics prevent serious bacterial infections in children at risk for occult bacteremia. METHODS: Meta-analysis of randomized controlled trials involving children aged 3 months to 36 months without a focus of infection and randomized into 2 treatment groups: 1) no antibiotic vs antibiotic or 2) IM ceftriaxone vs oral antibiotic. RESULTS: The use of either an oral antibiotic or IM ceftriaxone did trend toward a reduced risk of serious infection, although neither reached statistical significance (OR = 0.60; 95% CI 0.10, 3.49; and OR = 0.38; 95% CI 0.12, 1.17, respectively). It would be necessary to treat 414 patients to prevent 1 serious bacterial infection. When only children with proven occult bacteremia were analyzed, the use of IM ceftriaxone was statistically significant in preventing serious bacterial infections (OR = 0.25; 95% CI 0.07, 0.89). CONCLUSIONS: Clinical judgment should not be replaced by widespread antibiotic use in the approach to a child with fever. If rapid methods to identify children with occult bacteremia, such as polymerase chain reaction, could be improved and become widely available, then antibiotics could be used judiciously on initial visits. Antibiotic use in all children at risk for occult bacteremia implies the treatment of many children unlikely to benefit from such therapy.

Administration, Oral↗

Parenteral vs oral antibiotics in the prevention of serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia: a meta-analysis.

OBJECTIVE: To determine whether parenteral antibiotics are superior to oral antibiotics in preventing serious bacterial infections in children with Streptococcus pneumoniae occult bacteremia. METHODS: Using the MEDLINE database, the English language literature was searched for all publications concerning bacteremia, fever, or Streptococcus pneumoniae from 1966 to January 1, 1997. All nonduplicative studies with a series of children with S. pneumoniae occult bacteremia having both orally treated and parenterally treated groups were reviewed. Children were excluded from individual studies if at the time of their initial evaluation they were immunocompromised, had a serious bacterial infection, underwent a lumbar puncture, or did not receive antibiotics. RESULTS: Only 4 studies met study criteria. From these studies, 511 total cases of S. pneumoniae occult bacteremia were identified. Ten of 290 (3.4%) in the oral group and 5 of 221 (2.3%) in the parenteral antibiotic group developed serious bacterial infections (pooled p-value = 0.467, pooled OR = 1.48; 95% CI, 0.5-4.3). Two patients in the oral group (0.7%) and 2 patients in the parenteral group (0.9%) developed meningitis (pooled p-value = 0.699, pooled OR = 0.67; 95% CI, 0.1-5.1). CONCLUSION: The rates of serious bacterial infections and meningitis did not differ between children who were treated with oral and parenteral antibiotics. The extremely low rate of complications observed in both groups suggests no clinically significant difference between therapies. A study with >7,500 bacteremic children (or >300,000 febrile children) would be needed to have 80% power to prove parenteral antibiotics are superior to oral antibiotics in preventing serious bacterial infections.

Administration, Oral↗

[Decrease of nosocomial bacteremia and nosocomial pneumonia after introduction of preventive measures of hospital infection].

In the early 1980's methicillin-resistant staphylococcus aureus (MRSA) was reported as a major pathogenic organism of geriatric hospital infection in Japan. At the same time in the A geriatric hospital MRSA infection was prevalent. To decrease nosocomial infections some active preventive measures against hospital infection were taken since Oct. 1991. About a year before introduction of prevention of hospital infection in the geriatric ward (190 beds) of A hospital 193 episodes of nosocomial bacteremia were observed. However a year after introduction of preventive measures episodes of nosocomial bacteremia were decreased to less than a half (45.6%) in comparison to the number before introduction of prevention. As a causative organism gram-positive bacteria including MRSA were markedly decreased. Major portals of entry of bacteremia (74.9%) were urinary-tract system, intravenous hyperalimentation (IVH) catheter, and pressure sores. MRSA-positive pressure sores were decreased to 20.4% of those before prevention. On the other hand 87 episodes of nosocomial pneumonia were observed before prevention. However a year after introduction of preventive measures episodes of nosocomial pneumonia were decreased to less than a half (44.8%) in comparison to the number before introduction of prevention. After prevention MRSA and mixed infection of P. aeruginosa and MRSA were markedly decreased. The decrease of bacteremia and nosocomial pneumonia were caused by cleaning hands, the preventive measures for decrease and improvement of pressure sores, cleaning the upper respiratory tract for prevention of lower respiratory-tract infection cleaning floors and education of the staff, etc.

Adult↗

[Study of Streptococcus pneumoniae bacteremia in children].

From July 1999 to June 2004, we evaluated Streptococcus pneumoniae bacteremia in 40 children in Kamikawa and Soya Subprefectures in Hokkaido by obtaining the patient's information from 7 out of 9 hospitals in the area. The incidences of S. pneumoniae bacteremia in children aged < 2 years and < 5 years were 79.1 and 63.4. Median age was 19.6 months with a range from 4 months to 4 years. Thirty-one (77.5%) of the total were less than 2 years old. All of the children were admitted. The diagnoses were occult bacteremia in 12 patients, pneumonia or bronchitis in 11, pharyngitis in 7, pneumonia and acute otitis media in 5, acute otitis media in 3, orbital cellulitis in 1, and arthritis in 1. All of the patients had fever and temperatures and 35 (87.5%) of them were more than 39 degrees C. Ten patients had a febrile convulsion. Twenty-nine had a high total white blood cell counts (> 15,000/microg/ml) and 31 had positive CRP values (> 0.6 mg/dl) on admission. Meningitis and poor prognosis did not occur after occult bacteremia in our patients. We studied the susceptibility to penicillin G in 22 strains of S. pneumoniae isolated from the children. One and 18 strains were penicillin-resistant (MIC > or = 2.0 microg/ml) and intermediate (MIC 0.1-1.0 microg/ml).

Bacteremia↗

[Severe community-acquired Acinetobacter baumannii bacteremia with unknown foci].

We report an unusual case of Acinetobacter baumannii (A. baumannii) bacteremia in a man without significant comorbidities. A 50-year-old man who noticed a sudden onset of high fever was admitted to Kobe Nishi City Hospital. After the admission, his condition deteriorated rapidly with development of shock, anuria and agitation. Antibiotic therapy with meropenem and amikacin was begun for suspected septic shock along with the mechanical ventilation and continuous hemodialysis. Venous blood cultures yielded A. baumannii. No definite source of bacteremia was detected. Intensive medical management was effective, and he was discharged on the 27th day. While the most common source of infection that leads to A. baumannii bacteremia is in the respiratory tract, community-acquired bacteremia with unknown foci is considered rare.

Acinetobacter Infections↗

Outbreak of vancomycin-, ampicillin-, and aminoglycoside-resistant Enterococcus faecium bacteremia in an adult oncology unit.

An outbreak of bacteremia caused by Enterococcus faecium with high-level resistance to vancomycin (MIC of > or = 256 micrograms/ml), ampicillin (MIC of > or = 64 micrograms/ml), and gentamicin or streptomycin (MIC of > or = 2,000 micrograms/ml) occurred in an adult oncology unit from June 1991 to May 1992. Active surveillance for the presence of this organism in stool or perianal cultures was begun in September 1991. Between June 1991 and May 1992, seven patients with bacteremia and 22 noninfected carriers of the organism in stool were identified. The vanA gene, tested for by PCR and gene probe, was present in all isolates evaluated. All bacteremic patients also had resistant E. faecium present in a stool or perianal culture; the stool isolates tested were closely related to the respective blood isolates as determined by pulsed-field gel electrophoresis. Antibiotic regimens using high-dose ampicillin and an aminoglycoside were ineffective with four patients. Five patients (71%) had multiple positive blood cultures; four of these patients died. Following a multiple logistic regression analysis, it was found that bacteremic patients received a significantly greater number of total antibiotic days compared with noninfected stool carriers (P = 0.019). The emergence of E. faecium with high-level resistance to vancomycin, ampicillin, and aminoglycosides underscores the importance of performing susceptibility testing on all clinically significant isolates. In the neutropenic adult oncology patient, bacteremia with this organism is of probable gastrointestinal origin, is often persistent, and is refractory to treatment with ampicillin in combination with an aminoglycoside. Prolonged use of antibiotics may predispose patients with gastrointestinal colonization to develop bacteremia.

Adult↗

Randomized open trial of gentamicin and doxycycline for eradication of Bartonella quintana from blood in patients with chronic bacteremia.

Chronic Bartonella quintana bacteremia is known to occur in homeless people exposed to lice. We present here the results of an open randomized trial performed to evaluate the efficacy of doxycycline in combination with gentamicin in the eradication of B. quintana bacteremia. From 1 January 2001 to 1 April 2002, homeless people with blood cultures positive for B. quintana were randomized to receive either no treatment (untreated controls) or a combination of gentamicin (3 mg/kg of body weight/day intravenously for 14 days) and doxycycline (200 mg/day orally for 28 days). Patients were evaluated from the results of blood cultures performed between day 28 (the end of treatment) and day 90 postinclusion. Intention-to-treat analysis of 20 included patients showed eradication of bacteremia in 7 out of 9 treated patients versus 2 out of 11 untreated controls (P = 0.01). In the per-protocol analysis, eradication was obtained for 7 out of 7 treated patients versus 2 out of 9 untreated controls (P = 0.003). This study demonstrates the efficiency of the combination of doxycycline and gentamicin in eradicating B. quintana bacteremia.

Adult↗

Effectiveness of combination antimicrobial therapy for Pseudomonas aeruginosa bacteremia.

It remains controversial whether combination therapy, given empirically or as definitive treatment, for Pseudomonas aeruginosa bacteremia is associated with a better outcome than monotherapy. The aim of the present study was to compare the rates of survival among patients who received either combination therapy or monotherapy for P. aeruginosa bacteremia. We assembled a historical cohort of 115 episodes of P. aeruginosa bacteremia treated with empirical antipseudomonal therapy between 1988 and 1998. On the basis of susceptibility testing of the bacteremic P. aeruginosa isolate, we defined categories of empirical treatment, including adequate combination therapy, adequate monotherapy, and inadequate therapy, as well as corresponding categories of definitive therapy. Neither the adequacy of the empirical treatment nor the use of combination therapy predicted survival until receipt of the antibiogram. However, the risk of death from the date of receipt of the antibiogram to day 30 was higher for both adequate empirical monotherapy (adjusted hazard ratio [aHR], 3.7; 95% confidence interval [CI], 1.0 to 14.1) and inadequate empirical therapy (aHR, 5.0; 95% CI, 1.2 to 20.4) than for adequate empirical combination therapy. Compared to adequate definitive combination therapy, the risk of death at 30 days was also higher with inadequate definitive therapy (aHR, 2.6; 95% CI, 1.1 to 6.7) but not with adequate definitive monotherapy (aHR, 0.70; 95% CI, 0.30 to 1.7). In this retrospective analysis the use of adequate combination antimicrobial therapy as empirical treatment until receipt of the antibiogram was associated with a better rate of survival at 30 days than the use of monotherapy. However, adequate combination antimicrobial therapy given as definitive treatment for P. aeruginosa bacteremia did not improve the rate of survival compared to that from the provision of adequate definitive monotherapy.

Aged↗

Pharmacokinetic-pharmacodynamic relationships describing the efficacy of oritavancin in patients with Staphylococcus aureus bacteremia.

Bloodstream infections due to antimicrobial-resistant Staphylococcus aureus occur with increasing frequency and represent an important cause of morbidity and mortality. To date, the evaluation of pharmacokinetic-pharmacodynamic relationships for efficacy among patients with bacteremia has been limited. The objectives of these analyses were to evaluate relationships between microbiological and clinical responses for patients with S. aureus bacteremia and exposures for oritavancin, a novel bactericidal glycopeptide in development. Bayesian oritavancin exposure predictions, following treatment with 5, 6.5, 8, or 10 mg/kg of body weight/day, were derived using a validated population pharmacokinetic model for 55 patients with S. aureus bacteremia. Using classification and regression tree analysis, a breakpoint of the percentage of the dosing interval duration for which free-drug concentrations were above the MIC (free-drug % time > MIC) of 22% was identified for microbiological response; the probabilities of success greater than or equal to and less than this value were 93% and 76%, respectively. Using logistic regression, a relationship was found between microbiological response and free-drug % time > MIC (odds ratio = 4.42, P = 0.09, and odds ratio = 8.84, P = 0.05, when one patient, a medical outlier, was excluded). A similar relationship was found for clinical response. These results will be valuable in supporting dose selection of oritavancin for patients with S. aureus bacteremia.

Anti-Bacterial Agents↗