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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, viridans streptococci have been reported with increasing frequency to cause infections in neutropenic cancer patients. Streptococcus mitis, one of the species included among viridans streptococci, is the most resistant to beta-lactam antibiotics in this group. Bacterial meningitis presenting without pleocytosis in the cerebrospinal fluid (CSF) is rare, and this situation could be confusing to physicians. It is also an uncommon infectious complication in leukemic patients with neutropenia. In patients with leukopenia caused by myelosuppression after chemotherapy, bacterial meningitis must be considered a possibility when a patient develops meningeal signs, even if no pleocytosis is found in the CSF. We report on a 6-year-old boy with leukemia and neutropenia who developed sepsis and meningitis caused by S. mitis with high-level resistance to penicillin and cephalosporins (MIC of both, >2 mg/l); he was a long-term survivor receiving chronic trimethoprim-sulfamethoxazole prophylaxis. The patient was successfully treated with a combination of vancomycin, ceftriaxone, and granulocyte-colony-stimulating factor.
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PMID:Successful treatment of meningitis caused by highly-penicillin-resistant Streptococcus mitis in a leukemic child. 1202 40

A novel antibacterial antibiotic, for which the name altersetin is proposed, was isolated from the culture broth of two endophytic Alternaria species. The relative and absolute configuration were assigned by NOESY or CD data, respectively. Altersetin is chemically related to equisetin and showed potent MIC against several pathogenic gram-positive bacteria, whereas gram-negative bacteria and pathogenic yeast were not or much less susceptible. Moderate in vivo efficiacy was observed for altersetin in a murine sepsis model.
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PMID:Altersetin, a new antibiotic from cultures of endophytic Alternaria spp. Taxonomy, fermentation, isolation, structure elucidation and biological activities. 1252 21

AM-112 [(1'R,5R,6R)-3-(4-amino-1,1-dimethyl-butyl)-6-(1'-hydroxyethyl)oxapenem-3-carboxylate] is a novel oxapenem compound which possesses potent beta-lactamase-inhibitory properties. Fifty-percent inhibitory concentrations (IC(50)s) of AM-112 for class A enzymes were between 0.16 and 2.24 micro M for three enzymes, compared to IC(50)s of 0.008 to 0.12 micro M for clavulanic acid. Against class C and class D enzymes, however, the activity of AM-112 was between 1,000- and 100,000-fold greater than that of clavulanic acid. AM-112 had affinity for the penicillin-binding proteins (PBPs) of Escherichia coli DC0, with PBP2 being inhibited by the lowest concentration of AM-112 tested, 0.1 micro g/ml. Ceftazidime was combined with AM-112 at 1:1 and 2:1 ratios in MIC determination studies against a panel of beta-lactamase-producing organisms. These studies demonstrated that AM-112 was effective at protecting ceftazidime against extended-spectrum beta-lactamase-producing strains and derepressed class C enzyme producers, reducing ceftazidime MICs by 16- and 2,048-fold. Similar results were obtained when AM-112 was combined with ceftriaxone, cefoperazone, or cefepime in a 1:2 ratio. Protection of ceftazidime with AM-112 was maintained against Enterobacter cloacae P99 and Klebsiella pneumoniae SHV-5 in a murine intraperitoneal sepsis model. The 50% effective dose of ceftazidime against E. cloacae P99 and K. pneumoniae SHV-5 was reduced from >100 and 160 mg/kg of body weight to 2 and 33.6 mg/kg, respectively, when it was combined with AM-112 at a 1:1 ratio. AM-112 demonstrates potential as a new beta-lactamase inhibitor.
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PMID:In vitro and in vivo activities of AM-112, a novel oxapenem. 1270 36

Streptococcus pneumoniae is a rarely recognized cause of neonatal sepsis. We present a recent case of S. pneumoniae bacteremia acquired on the first day of life in a neonate born at 30 weeks of gestation to a mother without prenatal care who had prolonged rupture of the membranes and received intravenous ampicillin prior to delivery. The isolate was resistant to penicillin, with a MIC of the drug of 4 microg/ml. The child responded to a 7-day course of intravenous vancomycin. S. pneumoniae was recovered from the vagina of the mother on a swab culture collected prior to delivery, and isolates from mother and child were confirmed to be identical on the basis of pulsed-field gel electrophoresis. Although neonatal sepsis due to the peripartum transmission of S. pneumoniae is rare, this case highlights the concern that increasing efforts to prevent group B streptococcus neonatal disease may lead to an increase in neonatal infections due to resistant organisms.
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PMID:Peripartum transmission of penicillin-resistant Streptococcus pneumoniae. 1273 96

Antimicrobial therapy of soft tissue infections in patients with sepsis sometimes lacks efficiency, despite the documented susceptibility of the causative pathogen to the administered antibiotic. In this context, impaired equilibration between the antibiotic concentrations in plasma and those in tissues in critically ill patients has been discussed. To characterize the impact of tissue penetration of anti-infective agents on antimicrobial killing, we used microdialysis to measure the concentration-versus-time profiles of levofloxacin in the interstitial space fluid of skeletal muscle in patients with sepsis. Subsequently, we applied an established dynamic in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate bacterial killing at the site of infection. The population mean areas under the concentration-time curves (AUCs) for levofloxacin showed that levofloxacin excellently penetrates soft tissues, as indicated by the ratio of the AUC from time zero to 8 h (AUC(0-8)) for muscle tissue (AUC(0-8 muscle)) to the AUC(0-8) for free drug in plasma (AUC(0-8 plasma free)) (AUC(0-8 muscle)/AUC(0-8 plasma free) ratio) of 0.85. The individual values of tissue penetration and maximum concentration (C(max)) in muscle tissue were highly variable. No difference in bacterial killing of a select Staphylococcus aureus strain for which the MIC was 0.5 microg/ml was found between individuals after exposure to dynamically changing concentrations of levofloxacin in plasma and tissue in vitro. In contrast, the decrease in the bacterial counts of Pseudomonas aeruginosa (MIC = 2 microg/ml) varied extensively when the bacteria were exposed to levofloxacin at the concentrations determined from the individual concentration-versus-time profiles obtained in skeletal muscle. The extent of bacterial killing could be predicted by calculating individual C(max)/MIC and AUC(0-8 muscle)/AUC(0-8 plasma free) ratios (R = 0.96 and 0.93, respectively). We have therefore shown in the present study that individual differences in the tissue penetration of levofloxacin may markedly affect target site killing of bacteria for which MICs are close to 2 microg/ml.
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PMID:Relevance of soft-tissue penetration by levofloxacin for target site bacterial killing in patients with sepsis. 1457 16

The current incidence of infective endocarditis (IE) is estimated as 7 cases per 100,000 population per year and continues to increase. The prognosis is significantly influenced by proper diagnosis and adequate therapy. In cases with unconfirmed IE, transesophageal echocardiography is the imaging technique of choice. Culture-negative endocarditis requires either termination of antimicrobial treatment initiated without mircobiological test results and reevaluation of blood samples or serological/molecular biological techniques to identify the causative organism. Antimicrobial therapy should be established only after quantitative sensitivity tests of antibiotics (minimal inhibitory concentrations, MIC) and guided by drug monitoring. In the first 3 weeks after primary manifestation, an index embolism is frequently followed by recurrencies. If vegetations can still be demonstrated by echocardiography after an embolic event, a surgical intervention should seriously be considered. Cerebral embolic events are no contraindication for cardiac surgery, as long as a cerebral bleeding has been excluded by cranial computed tomography immediately preoperatively and the operation is performed before a significant disturbance of the blood-brain barrier (<72 hours) has manifested. A significant prognostic improvement has also been demonstrated for patients with early surgical intervention suffering from myocardial failure due to acute valve incompetence, acute renal failure, mitral kissing vegetations in primary aortic valve IE, and in patients with sepsis persisting for more than 48 hours despite adequate antimicrobial therapy.
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PMID:New aspects of infective endocarditis. 1528 78

A model of mouse sepsis caused by a serotype 6B Streptococcus pneumoniae strain (amoxicillin MIC of 8 microg/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [C(max)]: 6.1 microg/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates </=20% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (C(max)/MIC ratio of <1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.
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PMID:Effects of amoxicillin subinhibitory concentrations on the cross-protection developed by pneumococcal antibodies in mouse sepsis caused by an amoxicillin-resistant serotype 6B Streptococcus pneumoniae strain. 1550 33

Incubation in CO(2) resulted in higher (> or =3 doubling dilution) MICs of telithromycin than those found in ambient air for 31.2% of 346 Streptococcus pneumoniae ermB-positive strains. An increased telithromycin MIC in CO(2) was not correlated with loss of its activity in the murine sepsis/peritonitis model.
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PMID:Influence of carbon dioxide on the MIC of telithromycin for Streptococcus pneumoniae: an in vitro-in vivo study. 1561 38

A dose-decreasing immunocompetent sepsis mouse model was used to evaluate the in vivo effect of levofloxacin, moxifloxacin and gemifloxacin, using a ciprofloxacin/levofloxacin susceptible serotype 6B strain (ciprofloxacin MIC: 1 mg/l) and two resistant serotype 14 and 19F strains with gyrA and parC point mutations (ciprofloxacin MICs of 32 and 64 mg/l, respectively). Significant higher in vivo activity was found for moxifloxacin and gemifloxacin than for levofloxacin against strains 1 and 2, and for gemifloxacin versus moxifloxacin or levofloxacin against strain 3. Gemifloxacin treatment resulted in 100% survival against strains 1 and 2(AUC0-24 h/MIC of 30 and 62) but against strain 3, survival was 60-80% (AUC0-24 h/MIC of 93). Similar AUC0-24 h/MIC values produced different therapeutic results suggesting that in vitro parameters other than the MIC could influence efficacy predictions based on in vitro susceptibility tests (MICs) or pharmacodynamic parameters (AUC0-24 h/MIC).
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PMID:In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. 1566 87

The Pseudomonas aeruginosa efflux pumps MexAB-OprM, MexCD-OprJ, and MexEF-OprN play an important role in susceptibility to fluoroquinolones in vitro. To determine if levofloxacin MICs arising from different levels of expression of efflux pumps result in a proportional reduction in the response to levofloxacin in vivo, isogenic strains of P. aeruginosa were tested with levofloxacin in two mouse models of infection (sepsis and neutropenic mouse thigh models). The levofloxacin 50% effective doses (ED(50)s) increased proportionally with the MICs for most strains. Similarly, the 24-h area under the concentration-time curve (AUC)/MIC ratio that resulted in 90% of the maximum bactericidal activity (90% E(max)) exceeded 75 for all strains except those with elevated MICs due to MexEF-OprN overexpression. In these strains, levofloxacin ED(50)s were 2- to 10-fold lower than the ED(50)/MIC ratios in the other strains and 90% E(max) AUC/MIC ratios were 2- to 4-fold lower than those predicted from pharmacodynamic modeling of efficacy against other strains. These data show that while the MexEF-OprN efflux pump can provide P. aeruginosa resistance to levofloxacin in vitro, it appears to be less efficient in providing resistance to levofloxacin in animal models of infection.
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PMID:Pharmacodynamics of levofloxacin against Pseudomonas aeruginosa with reduced susceptibility due to different efflux pumps: do elevated MICs always predict reduced in vivo efficacy? 1664 28


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