Bacterial Growth In Blood Research Articles

Assessment of optimal blood exposure time at 37 °C during in vitro tsetse flies feeding for quality production in mass-rearing colonies.

Control of African animal trypanosomosis is implemented through an integrated control strategy, with the sterile insect technique (SIT) as one of its components. The SIT requires mass rearing of tsetse fly colonies using an in vitro feeding system. The exposure of blood at 37 °C on heating plates over time can have an impact on the quality of fly productivity. In this study, we investigated the survival and fecundity of adult tsetse flies fed at 37 °C on 8 blood exposure times ranging from 30 min to 4 h with increments of 30 min (treatment 1, flies were fed 30 min after exposure to blood at 37 °C; treatment 2, 1 h and so on until treatment 8 [4 h after]) in order to determine the optimal exposure time. In addition, bacterial growth in blood from each treatment was assessed by agar culture at 37 °C for 72 h. The results showed that the adult female survival rates were similar regardless of the treatment. For males, only those of treatment 1 (30 min) showed a marginal lower survival than those of treatments 7 and 8 fed after 3 h 30 min and 4 h of blood exposure, respectively. Over the 4-h interval of blood exposure at 37 °C, the results showed that the number of pupae produced per initial female and pupal weight tended to increase with exposure time, but the differences were not significant. We discuss the implications of these results on tsetse mass rearing for the SIT program.

Vertical capacitance aptasensors for real-time monitoring of bacterial growth and antibiotic susceptibility in blood

For the treatment of bacteremia, early diagnosis and rapid antibiotic susceptibility tests (ASTs) are necessary because survival chances decrease significantly if the proper antibiotic administration is delayed. However, conventional methods require several days from blood collection to AST as it requires three overnight cultures, including blood culture, subculture, and AST culture. Herein, we report a more rapid method of sensing bacterial growth and AST in blood based on a vertical capacitance sensor functionalized with aptamers. Owing to their vertical structure, the influence of blood cells sunk by gravity on capacitance measurements were minimized. Thus, bacterial growth in blood at 100–103 CFU/mL was monitored in real-time by measuring changes in capacitance at f = 10 kHz. Moreover, real-time capacitance measurements at f = 0.5 kHz provided information on biofilm formation induced during blood cultures. Bacterial growth and biofilm formation are inhibited above the minimal inhibitory concentration of antibiotics; therefore, we also demonstrated that vertical capacitance aptasensors could be applied to rapid AST from positive blood cultures without a need for the subculture process.

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections

To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis). Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt. Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths. Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI.

Culture-free bacterial detection and identification from blood with rapid, phenotypic, antibiotic susceptibility testing

The current culture-based approach for the diagnosis of bloodstreams infection is incommensurate with timely treatment and curbing the prevalence of multi-drug resistant organisms (MDROs) due to its long time-to-result. Bloodstream infections typically involve extremely low (e.g., <10 colony-forming unit (CFU)/mL) bacterial concentrations that require a labor-intensive process and as much as 72 hours to yield a diagnosis. Here, we demonstrate a culture-free approach to achieve rapid diagnosis of bloodstream infections. An immuno-detection platform with intrinsic signal current amplification was developed for the ultrasensitive, rapid detection, identification (ID) and antibiotic susceptibility testing (AST) of infections. With its capability of monitoring short-term (1–2 hours) bacterial growth in blood, the platform is able to provide 84-minute simultaneous detection and ID in blood samples below the 10 CFU/mL level and 204-minute AST. The susceptible-intermediate-resistant AST capacity was demonstrated.

CD4 T cell-mediated immunopathology of a Staphylococcus aureus whole cell vaccine during systemic infection

Abstract Staphylococcus aureus causes a wide array of diseases, ranging from superficial skin infections to life threatening diseases like sepsis. Treatment is difficult due to emerging multidrug-resistant strains and importantly, several approaches to develop an efficacious vaccine have either failed or augmented disease in clinical trials. In the present study, gamma-irradiated S. aureus USA300 (IRS) was used as a whole-cell vaccine to evaluate the immune response towards vaccination and subsequent infection. C57BL/6 mice were vaccinated thrice intramuscularly, adjuvanted with or without Al(OH)3, at two-week intervals and challenged with USA300 intravenously 2 weeks after the last vaccination. Vaccination enhanced mortality and failed to control bacterial growth in blood and organs when compared to PBS controls and was worse without Al(OH)3. USA300-specific antibodies were induced by vaccination but did not cause enhanced mortality when tested in serum transfer studies. Furthermore, B cell deficient and WT mice were similarly susceptible to infection after vaccination. Infection increased frequency of CD44hiTbet+ and CD44hiIFNg+ (Th1 effector) cells in spleens of both vaccinated groups but was higher in mice vaccinated without Al(OH)3. Frequency of CD44hiRORgt+ and CD44hiIL-17+ (Th17 effector) cells increased only in groups vaccinated with Al(OH)3. Depletion of CD4 T cells during infection reversed the lethal phenotype. Similarly, neutralization of IFNg but not IL-17 during infection improved survival and reduced organ pathology. Taken together, our findings show a detrimental role for IFNg+CD4 Teff cells generated by vaccination with IRS, and might shed some light on recent vaccine failures.

Resistance of subacutely burned mice (SAB-mice) therapeutically treated with CCL1 antisense ODN against infections with MRSA or enterococci (INC4P.344)

Abstract In previous studies, sepsis stemming for E. faecalis translocation and MRSA local infection has been greatly controlled in SAB-mice prophylactically treated with CCL1 antisense ODN. Effector cells (M1Mφ) in host antibacterial immunities are isolated from the infected SAB-mice after treatment with the ODN. In this study, the antibacterial resistance of SAB-mice therapeutically treated with the ODN was examined against infections with E. faecalis and MRSA. Mice 2 weeks after flame burn injury (3rd degree 25% TBSA) were infected with MRSA (106 CFU/mouse, i.v.). Decontaminated mice 2 weeks after burn injury were infected with E. faecalis (8 x 106 CFU/mouse, p.o.). These mice were therapeutically treated with the ODN (s.c., 10 mg/mouse) at various schedules starting 12 h after the infection. The antibacterial efficacies of the ODN were evaluated by reducing bacterial growth in blood and organs as compared to those of control mice. In the results, bacteria grew in the blood (&amp;gt;105 CFU/ml), liver (&amp;gt;106 CFU/gram), spleen (&amp;gt;105 CFU/gram), and kidneys (&amp;gt;107 CFU/gram) of control mice 3 to 5 days after MRSA infection. However, significant growth of the pathogen in their organs was not demonstrated in SAB-mice treated with the ODN 12, 24, and 36 h after the infection. Similar results were obtained in SAB-mice orally infected with E. faecalis. These results indicate that infections with MRSA and E. faecalis in SAB-mice are controllable by the therapeutic treatment with CCL1 antisense ODN.

Bacteremia associated with bronchoscopy

ObjectiveTo assess the incidence of bacteremia following bronchoscopy to determine whether the use of prophylactic antibiotics is warranted in patients at risk of endocarditis. DesignProspective nonrandomized clinical study. SettingsBronchoscopy Unit of Chest Department and Thoracic Surgery Department, and Microbiology Laboratory of Ain Shams University Hospitals, Cairo, Egypt. PatientsForty-five patients undergoing diagnostic and therapeutic bronchoscopy. InterventionsBlood samples for culture were obtained before and immediately after the procedure. ResultsThere were no documented cases of bacterial growth in blood. Two culture bottles yielded contaminant. ConclusionBronchoscopy is a low-risk procedure for the development of bacteremia. This may bear on present practice regarding perioperative antibiotic prophylaxis for endocarditis in the high-risk groups.

Thalidomide prolongs survival after experimental musculoskeletal injury, through an effect on mononuclear apoptosis

BackgroundThis study was conducted to investigate the effects of intravenous thalidomide administration in an experimental model of musculoskeletal trauma. We hypothesized that because thalidomide inhibits secretion of tumor necrosis factor alpha (TNF-α), survival of animals that received thalidomide would be significantly prolonged. Material and methodsAfter an open fracture of the right femur, 24 rabbits were randomly assigned to control and thalidomide groups. Intravenous therapy with thalidomide was started 30 min after fracture. Hemodynamic monitoring of all animals was performed for 4 h. Survival was recorded and bacterial growth in blood and organs was measured after animal death or sacrifice. Blood was sampled for TNF-α measurement and for isolation of peripheral blood mononuclear cells (PBMCs). Apoptosis of PBMCs was measured by flow cytometry. ResultsSurvival was significantly prolonged in the thalidomide group. Apoptosis of PBMCs was increased in the control group compared with the thalidomide group at 24 h. There were no differences in vital signs, blood and tissue cultures, and serum TNF-α concentration between the two groups. ConclusionsIntravenous thalidomide prolonged survival in an experimental model of severe musculoskeletal injury in rabbits. Its mechanism of action did not involve TNF-α suppression but prevention of mononuclear apoptosis. In view of these promising results, further research is needed to clarify the immunomodulatory mechanism of action of thalidomide and its potential use for the management of severe trauma.

Infecções relacionadas a cateteres torácicos

To determine the incidence of local and systemic infection in a sample of patients catheterized with thoracic catheters (TCs) and to identify the prognostic factors for catheter-related infection. A retrospective study involving 48 patients (17 females and 31 males) catheterized with TCs between December of 2008 and March of 2009 in the Thoracic Surgery Department of the Adnan Menderes University Hospital, located in Aydin, Turkey. Blood samples for culture were collected from the distal end of each TC and from each of the 48 patients. We looked for correlations between positive culture and possible prognostic factors for catheter-related infection. Culture results were positive in TC samples only for 3 patients, in blood samples only for 2, and in both types of samples for another 2. Advanced age correlated significantly with positive culture in TC samples and in blood samples (r = 0.512 and r = 0.312, respectively; p < 0.05 for both), as did prolonged catheterization (r = 0.347 and r = 0.372, respectively; p < 0.05). There was a significant correlation between having undergone surgery and positive culture in TC samples only (p < 0.05). However, having an inoperable malignancy correlated with bacterial growth in blood and in TC samples alike (p < 0.05 for both). Risk factors, such as advanced age, prolonged catheterization, comorbidities, and inoperable malignancy, increase the risk of catheter-related infection. It is imperative that prophylaxis with broad-spectrum antibiotics be administered to patients who present with these risk factors and might be catheterized with a TC.

Protective Effect of Citropin 1.1 and Tazobactam-Piperacillin Against Oxidative Damage and Lethality in Mice Models of Gram-Negative Sepsis

Gram-negative sepsis ranks as the leading cause of death in intensive care units, and its incidence is increasing steadily and mortality rates has not changed much over recent decades. We investigated the efficacy of the amphibian peptide, citropin 1.1 alone and in combination with tazobactam-piperacillin (TZP) in two experimental mice models of gram-negative sepsis. Animals were given an intraperitoneal injection of (1) 1 mg Escherichia coli 0111:B4 LPS, and (2) 2×10(10) CFU of E. coli ATCC 25922. For each model, all animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/Kg citropin 1.1 and 120 mg/Kg of TZP, and finally 1 mg/Kg citropin 1.1 plus 60 mg/Kg of TZP. Lethality, bacterial growth in blood and peritoneum, and oxidative stress indices in plasma were evaluated. All compounds reduced the lethality compared with controls. Treatment with citropin 1.1 resulted in significant decrease in plasma endotoxin and cytokine levels, while TZP exerted opposed effect. The combination between citropin 1.1 and TZP proved to be the most effective treatment in reducing all variables measured. Due to its multifunctional properties, citropin 1.1 may become an important future consideration to treat conditions in which oxidative organ failure may be present.

S-thanatin enhances the efficacy of tigecycline in an experimental rat model of polymicrobial peritonitis

We investigated the efficacy of the peptide s-thanatin alone and in combination with tigecycline in an animal model of sepsis induced by cecal ligation and puncture. Adult male Wistar rats were randomized to receive intravenously isotonic sodium chloride solution, 5mg/kg s-thanatin, 2mg/kg tigecycline, 5mg/kg s-thanatin combined with 2mg/kg tigecycline. The experiment was also performed with administration of the drugs 360 min after the surgical procedure to better investigate the clinical situation where there is an interval between the onset of sepsis and the initiation of therapy. Lethality, bacterial growth in blood, peritoneum, spleen and liver, and NO indices were evaluated. All compounds reduced the lethality when compared to control. In all experiments, the compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with s-thanatin resulted in significant decrease in plasma NO levels compared to tigecycline and control group. The combination between s-thanatin and tigecycline proved to be the most effective treatment in reducing all variables measured. S-thanatin may have potential therapeutic usefulness alone and when associated to tigecycline in polymicrobial peritonitis.

Therapeutic efficacy of buforin II and rifampin in a rat model of Acinetobacter baumannii sepsis

To investigate the efficacy of buforin II and rifampin in an experimental rat model of Acinetobacter baumannii sepsis. Prospective, randomized, controlled animal study. Research laboratory in a university hospital. Adult male Wistar rats. The animals received intraperitoneally 1 mL saline containing 2 x 10 colony forming units of A. baumannii ATCC 19606 (model i) or the multiresistant strain (model ii). Immediately after bacterial challenge, animals received intravenously a single dose of isotonic sodium chloride solution (control groups C1 and C2), 1 mg/kg of buforin II, 10 mg/kg of rifampin, and 1 mg/kg of buforin II plus 10 mg/kg of rifampin, respectively. Lethality, bacterial growth in blood and tissue burden, endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma. Buforin II showed good antimicrobial activity and achieved a significant reduction of plasma endotoxin and cytokines concentration when compared with control and rifampin-treated groups. Combination among buforin II proved to be the most effective treatment in reducing all variables measured. In an experimental model, buforin II and rifampin might have a potential role in the treatment of severe infections due to A. baumannii.

EFFICACY OF LL-37 AND GRANULOCYTE COLONY-STIMULATING FACTOR IN A NEUTROPENIC MURINE SEPSIS DUE TO PSEUDOMONAS AERUGINOSA

A promising therapeutic strategy for the management of severe Pseudomonas infection in neutropenic patients may result from the coadministration of colony-stimulating factors (CSFs) that help maintain immune competence and antimicrobial peptides, a novel generation of adjunctive therapeutic agents with antimicrobial and anti-inflammatory properties. A promising peptide with these properties is LL-37, the only member of the cathelicidin family of antimicrobial peptides found in humans. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 preinfection. Septic shock was induced at time 0 by intraperitoneal injection of 2x10 colony-forming units of P. aeruginosa American Type Culture Collection (ATCC) 27853. All animals were randomized to receive intravenously isotonic sodium chloride solution, 1 mg/kg of LL-37, 20 mg/kg of imipenem, 0.1 mg/kg of granulocyte CSF (G-CSF), 1 mg/kg of LL-37+0.1 mg/kg of G-CSF, or 20 mg/kg of imipenem+0.1 mg/kg of G-CSF. Lethality and bacterial growth in blood, peritoneum, spleen, liver, and kidney were evaluated. All regimens were significantly superior to controls at reducing the mouse lethality rate and bacterial burden in organs. Particularly, the combination between LL-37 and G-CSF was the most effective in protecting neutropenic mice from the onset of sepsis and in vitro significantly reduced the apoptosis of neutrophils. Combination therapy between LL-37 and G-CSF is a promising therapeutic strategy for the management of severe Pseudomonas infection complicated by neutropenia.

Protective effects of the combination of α-helical antimicrobial peptides and rifampicin in three rat models of Pseudomonas aeruginosa infection

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A with or without rifampicin against control and multidrug-resistant Pseudomonas aeruginosa strains. In vitro experiments included MIC determinations and synergy studies. For in vivo studies, animals were given an intraperitoneal injection of P. aeruginosa lipopolysaccharide, P. aeruginosa ATCC 27853 and one clinical multiresistant P. aeruginosa strain. Groups of animals received intravenously isotonic sodium chloride solution, 10 mg/kg rifampicin, 1 mg/kg magainin II or 1 mg/kg cecropin A. Two groups of animals received a combined treatment with magainin II + rifampicin or cecropin A + rifampicin at the same dosages as the singly treated groups. In addition, a further group was treated with tazobactam/piperacillin (120 mg/kg). Lethality, bacterial growth in blood and peritoneum, and endotoxin and TNF-alpha concentrations in plasma were evaluated. Combinations of alpha-helical antimicrobial peptides showed in vitro synergistic interaction. Magainin II and cecropin A exerted strong antimicrobial activity and achieved a significant reduction in plasma endotoxin and TNF-alpha concentrations when compared with control and rifampicin-treated groups. Rifampicin exhibited no anti-P. aeruginosa activity and good substantial impact on endotoxin and TNF-alpha plasma concentrations. Combined treatment groups had significant reductions in bacterial count, positive blood cultures and mortality rates when compared with singly treated and control groups. Our results highlight the potential usefulness of these combinations that provide future therapeutic alternatives in P. aeruginosa infections.

Efficacy of the amphibian peptide distinctin in a neutropenic mouse model of staphylococcal sepsis

To investigate the efficacy of distinctin in a neutropenic mouse model of staphylococcal sepsis. Prospective, randomized, and controlled animal study. Research laboratory in a University Hospital. BALB/c male mice. Mice were rendered neutropenic by injecting cyclophosphamide (200 mg/kg of body weight/day) on days -4 and -2 preinfection. Infection was induced at time 0 by intraperitoneal injection of 1 x 10(9) colony forming units of the staphylococcal strain. For each model, all animals were randomized to receive intravenous isotonic sodium chloride solution, 1 mg/kg distinctin, and 10 mg/kg imipenem, 10 mg/kg vancomycin, 10 mg/kg teicoplanin or 10 mg/kg linezolid alone, or combined with 1 mg/kg distinctin. Lethality, bacterial growth in blood and peritoneum, spleen, liver, and mesenteric lymph nodes. All combined regimen showed lower lethality rates than singly treated-groups. Distinctin plus vancomycin or teicoplanin exerted the lowest lethality rate. All regimens were significantly superior to controls at reducing blood, spleen, peritoneum, liver and mesenteric lymph node complex bacterial burdens, whereas all combined treated groups were higher effective than singly treated groups. Our data indicate that distinctin alone or combined with other antibiotics may be useful in treating severe staphylococcal infections.

Rapid Eradication of Listeria monocytogenes by Moxifloxacin in a Murine Model of Central Nervous System Listeriosis

Listeriosis is a rare but life-threatening infection. A favorable outcome is greatly aided by early administration of antibiotics with rapid bactericidal activity against Listeria monocytogenes. Moxifloxacin, a new-generation fluoroquinolone with extended activity against gram-positive bacteria, has proved its effectiveness in vitro against intracellular reservoirs of bacteria. The efficacies of moxifloxacin and amoxicillin were compared in vivo by survival curve assays and by studying the kinetics of bacterial growth in blood and organs in a murine model of central nervous system (CNS) listeriosis. We combined pharmacokinetic and pharmacodynamic approaches to correlate the observed efficacy in vivo with plasma and tissue moxifloxacin concentrations. Death was significantly delayed for animals treated with a single dose of moxifloxacin compared to a single dose of amoxicillin. We observed rapid bacterial clearance from blood and organs of animals treated with moxifloxacin. The decrease in the bacterial counts in blood and brain correlated with plasma and cerebral concentrations of antibiotic. Moxifloxacin peaked in the brain at 1.92 +/- 0.32 microg/g 1 hour after intraperitoneal injection. This suggests that moxifloxacin rapidly crosses the blood-brain barrier and diffuses into the cerebral parenchyma. Moreover, no resistant strains were selected during in vivo experiments. Our results indicate that moxifloxacin combines useful pharmacokinetic properties and rapid bactericidal activity and that it may be a valuable alternative for the treatment of CNS listeriosis.

Nucleotide Biosynthesis Is Critical for Growth of Bacteria in Human Blood

Proliferation of bacterial pathogens in blood represents one of the most dangerous stages of infection. Growth in blood serum depends on the ability of a pathogen to adjust metabolism to match the availability of nutrients. Although certain nutrients are scarce in blood and need to be de novo synthesized by proliferating bacteria, it is unclear which metabolic pathways are critical for bacterial growth in blood. In this study, we identified metabolic functions that are essential specifically for bacterial growth in the bloodstream. We used two principally different but complementing techniques to comprehensively identify genes that are required for the growth of Escherichia coli in human serum. A microarray-based and a dye-based mutant screening approach were independently used to screen a library of 3,985 single-gene deletion mutants in all non-essential genes of E. coli (Keio collection). A majority of the mutants identified consistently by both approaches carried a deletion of a gene involved in either the purine or pyrimidine nucleotide biosynthetic pathway and showed a 20- to 1,000-fold drop in viable cell counts as compared to wild-type E. coli after 24 h of growth in human serum. This suggests that the scarcity of nucleotide precursors, but not other nutrients, is the key limitation for bacterial growth in serum. Inactivation of nucleotide biosynthesis genes in another Gram-negative pathogen, Salmonella enterica, and in the Gram-positive pathogen Bacillus anthracis, prevented their growth in human serum. The growth of the mutants could be rescued by genetic complementation or by addition of appropriate nucleotide bases to human serum. Furthermore, the virulence of the B. anthracis purE mutant, defective in purine biosynthesis, was dramatically attenuated in a murine model of bacteremia. Our data indicate that de novo nucleotide biosynthesis represents the single most critical metabolic function for bacterial growth in blood and reveal the corresponding enzymes as putative antibiotic targets for the treatment of bloodstream infections.

Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis

To investigate the efficacy of piperacillin/tazobactam combined with indolicidin in the prevention of lethality in two rat models of polymicrobial peritonitis. Prospective, randomized, controlled animal study. Research laboratory in a university hospital. Adult male Wistar rats. Adult male Wistar rats were given an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 lipopolysaccharide or had intraabdominal sepsis induced by cecal ligation and puncture. For each model, all animals were randomized to receive isotonic sodium chloride solution intraperitoneally, 1 mg/kg indolicidin, 120 mg/kg piperacillin/tazobactam, and 1 mg/kg indolicidin combined with 120 mg/kg piperacillin/tazobactam. Each group included 20 animals. Main outcome measures were: bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma; and lethality. All compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with indolicidin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas piperacillin/tazobactam exerted the opposite effect. The combination between indolicidin and piperacillin/tazobactam proved to be the most effective treatment in reducing all variables measured. Indolicidin may have potential therapeutic usefulness alone and when associated with piperacillin/tazobactam in polymicrobial peritonitis.

Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of tazobactam/piperacillin in a neutropenic mouse model of polymicrobial peritonitis

We investigated the efficacy of tazobactam/piperacillin (TZP), tachyplesin III and granulocyte-colony stimulating factor (G-CSF) in an experimental murine neutropenic intraabdominal infection. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days −4 and −2 pre-infection. Septic shock was induced by cecal ligation and puncture . Animals received intravenously isotonic sodium chloride solution (control group C 1), 1 mg/kg of tachyplesin III, 120 mg/kg of TZP, 0.1 mg/kg of G-CSF, tachyplesin III plus TZP, G-CSF plus TZP and finally tachyplesin III plus G-CSF plus TZP, respectively. Lethality, bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes, endotoxin, IL-6 and TNF-alpha concentrations in plasma were evaluated. All compounds reduced the lethality when compared to controls. Endotoxin and cytokine plasma levels were significantly higher in TZP-treated animals compared to tachyplesin III-treated animals. Finally, all drug combinations showed to be the most effective treatment in reducing all variables measured. Interestingly, the strongest results concerning the bacterial growth inhibition, lethality and endotoxemia were obtained when the three compounds were contemporaneously administered. The presence of their positive interaction makes tachyplesin III and G-CSF potentially valuable as an adjuvant for antimicrobial chemotherapy of sepsis.

Efficacy of colistin/rifampin combination in experimental rat models of sepsis due to a multiresistant Pseudomonas aeruginosa strain*

To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis. Prospective, randomized, controlled animal study. Research laboratory in a university hospital. Adult male Wistar rats. Adult male Wistar rats were given a) an intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysaccharide; b) 2 x 10(10) colony-forming units of P. aeruginosa ATCC 27853; and c) 2 x 10(10) colony-forming units of one clinically multiresistant strain of P. aeruginosa. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 10 mg/kg rifampin, 1 mg/kg colistin, and 10 mg/kg rifampin plus 1 mg/kg colistin. Lethality, bacterial growth in blood and peritoneum, and endotoxin and tumor necrosis factor-alpha concentrations in plasma were measured. Colistin exerted a strong antimicrobial activity and achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration compared with control and rifampin-treated groups. Rifampin exhibited no antimicrobial activity with no substantial impact on endotoxin and tumor necrosis factor-alpha plasma concentrations. The combination of colistin and rifampin resulted in a significant reduction in bacterial count compared with colistin monotherapy, whereas no significant difference was found in positive hem cultures and mortality rates between the two groups. Colistin and rifampin might have a role in the therapy of multiresistant P. aeruginosa infection.