Safety of parenteral third-generation cephalosporins

Knowledge of side effects associated with different cephalosporins may be of help to prescribers. There are several side effects that are common to all cephalosporins, but overall, cefotaxime and ceftizoxime cause the fewest adverse reactions. Bleeding is probably the most common serious side effect of cephalosporins. Moxalactam causes coagulopathy and bleeding more often than do other cephalosporins, probably because it is carboxylated and has a methylthiotetrazole side chain. Cefoperazone also has a methylthiotetrazole side chain and may cause bleeding, particularly when used in doses greater than 4 g per day. Ceftriaxone has a similar side chain and there is some evidence that it can induce a coagulopathy. Coagulation tests should be monitored when any of the third-generation cephalosporins are given to patients with a high risk of bleeding. Disulfiram-like reactions are also related to the side chains associated with coagulation defects and have been reported when patients receiving cefoperazone, moxalactam, or ceftriaxone have ingested alcohol. Seizures have been reported with ceftazidime, but are uncommon. Hematologic reactions are rare with all third-generation cephalosporins. Benign diarrhea and Clostridium difficile colitis probably occur most often with moxalactam, cefoperazone, ceftazidime, and ceftriaxone, but there are few good data on this issue. Ceftriaxone has the unique ability to cause sludge (also referred to as pseudolithiasis) to form in the gallbladder, particularly in children. This may be associated with nausea, anorexia, epigastric distress, and colic, and is usually detected using ultrasonography. The sludge dissolves and symptoms subside after therapy is discontinued. None of the third-generation cephalosporins is clearly significantly nephrotoxic, even when combined with aminoglycosides. Most of the third-generation cephalosporins have surprisingly few serious side effects, which make them attractive for use in the treatment of a wide variety of serious infections.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28621/1/0000434.pd

Immunoglobulin G directed against toxins A and B of Clostridium difficile in the general population and patients with antibiotic-associated diarrhea

Serum immunoglobulin G (IgG) class antibodies directed against toxins A and B of Clostridium difficile were studied using an enzyme-linked immunosorbent assay and a serum-neutralizing assay based on the MRC-5 tissue cytotoxicity assay. Of 185 individuals, 46 sera (24%) in the general population demonstrated IgG antibody, 36 (19.4%) against toxin A and 15 (8.1%) against toxin B. Antibody titer in the general population did not correlate with serum-neutralizing activity. Antibody prevalence fell with age (P = 0.58) over 50 years. Six of ten patients with acute primary episodes of C. difficile-associated diarrhea demonstrated antibody in convalescentphase sera, predominantly directed against toxin B. Only two (28%) of seven patients with a history of relapsing C. difficile disease had demonstrable antibody.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31662/1/0000596.pd

Pseudomonas aeruginosa endocarditis in drug addicts

Six intravenous heroin users with P. endocarditis were seen between 1970 and 1972. Five out of six (83 per cent) had tricuspid valvulitis. Fever and a significant murmur were found in all cases, a subacute presentation and splenomegaly were found in 83 per cent, and chest pain with cavitating infiltrates on x-ray was observed in 67 per cent. Three patients died of infection. Three patients survived; one was cured with medical therapy alone, and two required surgical removal of the infected valve as well. The success of surgical ablation of the tricuspid valve in these patients is encouraging, particularly in view of their poor response before surgery to combinations of antibiotics with proved in vitro efficacy. Prior bacteremia with more virulent organisms may be important in the pathogenesis of endocarditis with Pseudomonas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22243/1/0000679.pd

RIFAMPICIN AND ANTIBIOTIC-ASSOCIATED COLITIS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24457/1/0000731.pd

ANTIBIOTIC-INDUCED COLITIS IMPLICATION OF A TOXIN NEUTRALISED BY CLOSTRIDIUM SORDELLII ANTITOXIN

A toxin(s) has been demonstrated in the stools of two patients with antibiotic- associated colitis. This toxin(s) was heat-labile, wasrapidly lethal for hamsters, increased vascular permeability in rabbit skin, and was cytotoxic for cells in tissue-culture. It was neutralised by Clostridium sordellii antitoxin but not by antitoxins prepared against otherclostridia; Escherichia coli, and Vibrio choleroe toxins. These characteristics were identical to those of a toxin implicated in the aetiology of antibiotic-induced colitis in the hamster. One patient improved rapidly after treatment with oral vancomycin, and at the same time the toxin disappeared from the stool.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22808/1/0000365.pd

Aboveground biomass density models for NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission

NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (similar to 25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available