Evidence suggests that drug-induced gastrointestinal (GI) injury is common, with a wide range of medications implicated, but an accurate estimate of the incidence of adverse GI reactions to drugs is difficult to obtain. Data from the United States (Food and Drug administration) show that 18 percent of all adverse reactions reported to that agency were related to the GI tract.1 Diarrheal episodes are classically distinguished into acute and chronic (or persistent) based on their duration. Acute diarrhea is thus defined as an episode that has an acute onset and lasts no longer than 14 days; chronic or persistent diarrhea is defined as an episode that lasts longer than 14 days. The distinction, supported by the World Health Organization (WHO), has implications not only for classification and epidemiological studies but also from a practical standpoint because protracted diarrhea often has a different set of causes, poses different problems of management, and has a different prognosis. Drugs can induce intestinal injury or dysfunction through single or multiple mechanisms. The more common mechanisms of drug induced bowel injury are listed below. This discussion covers antibiotic agents that have been associated with some effect.

Clinical practice. Antibiotic-associated diarrhea.

Background: Recent reports suggest that Clostridium difficile colitis may be evolving into a more severe disease. During the second half of 2002 we noted an increase in the number of patients with severe C. difficile -associated diarrhea (CDAD) in our institution. We describe cases of CDAD at our institution over a 13-year period and investigate changes in illness severity. Methods: We undertook a retrospective chart review of all cases of CDAD diagnosed at the Centre hospitalier universitaire de Sherbrooke from Jan. 1, 1991, to Dec. 31, 2003. Because the hospital serves a well-defined population of Quebec, we were also able to calculate population-based incidence during this period. We abstracted data on individual patients from patient charts and from hospital and pharmacy computer databases. We defined cases of CDAD as having a positive C. difficile cytotoxicity assay result, or endoscopic or histopathological evidence of pseudomembranous colitis. A case was considered complicated if one or more of the following was observed: megacolon, perforation, colectomy, shock requiring vasopressor therapy, or death within 30 days after diagnosis. Results: A total of 1721 cases of CDAD were diagnosed during the study period. The incidence increased from 35.6 per 100 000 population in 1991 to 156.3 per 100 000 in 2003; among patients aged 65 years or more, it increased from 102.0 to 866.5 per 100 000. The proportion of cases that were complicated increased from 7.1% (12/169) in 1991–1992 to 18.2% (71/390) in 2003 ( p p 9 /L or greater) and an elevated creatinine level (200 μmol/L or greater) were strongly associated with adverse outcomes: in 2003, 45 (40.9%) of 110 patients with a high leukocyte count or creatinine level, or both, had complicated CDAD and 28 (25.5%) died within 30 days after diagnosis. After adjustment for age and other confounding factors, patients initially given oral vancomycin therapy had a risk of progression to complicated CDAD that was 79% lower than the risk among patients initially treated with metronidazole (adjusted odds ratio 0.2, 95% confidence interval 0.06–0.8, p = 0.02). Interpretation: An epidemic of CDAD with an increased case-fatality rate has had important consequences on the elderly population of our region. Our observational data suggest that the equivalence of vancomycin and metronidazole in the treatment of CDAD needs to be questioned.

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Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity

Summary
Candida albicans is an opportunistic pathogen that is commonly found as a member of the human microflora. The ability of C. albicans to alter its cellular morphology has been associated with its virulence; yeast cells are more prevalent in commensal interactions whereas filamentous cells appear important in opportunistic infections. C. albicans encounters a multitude of other microbial species in the host environment and it is likely that they impact the C. albicans transition between virulent and non-virulent states. Here, we report that C. albicans morphology is significantly affected by the presence of Pseudomonas aeruginosa, another opportunistic pathogen. In a screen using a C. albicans HWP1–lacZ strain to indicate regions of filamentous growth, we identified P. aeruginosa mutants incapable of inhibiting C. albicans filamentation. Through these studies, we found that 3-oxo-C12 homoserine lactone, a cell–cell signalling molecule produced by P. aeruginosa, was sufficient to inhibit C. albicans filamentation without affecting fungal growth rates. Both microscopic analysis and real-time reverse transcription polymerase chain reaction analysis of morphology-specific markers confirmed that filamentation was suppressed by 200 µM 3-oxo-C12 homoserine lactone. Structurally related compounds with a 12-carbon chain length, e.g. C12-acyl homoserine lactone and dodecanol also affected C. albicans filamentation at similar concentrations. In contrast, other acylated homoserine lactones of different chain lengths did not affect fungal morphology. The activity of 3OC12HSL is compared with that of farnesol, a C. albicans-produced molecule also with a C12-backbone. The effects that bacteria have on the morphology of C. albicans represents one of the ways by which bacteria can influence the behaviour of fungal cells.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2958.2004.04349.x

A Pseudomonas aeruginosa quorum-sensing molecule influences Candida albicans morphology.

Background: Glycohemoglobin (gHb), measured as hemoglobin (Hb) A1c or as total gHb, provides a common means for assessing long-term glycemic control in individuals with diabetes mellitus. Genetic variants and chemically modified derivatives of Hb can profoundly affect the accuracy of these measurements, although effects vary considerably among commercially available methods. The prevalence of genetic variants such as HbS, HbC, and HbE, and chemically modified derivatives such as carbamyl-Hb among patient populations undergoing testing is not insignificant. Clinical laboratories and sites responsible for point-of-care testing of gHb need to be aware of the interferences produced in assays by these Hbs.

Approach: We conducted a review of the literature describing the effects of variant Hbs on gHb assay methods commonly used in clinical laboratories.

Content: This review summarizes the documented effects of both common and uncommon Hb variants and derivatives on the measurement of gHb. Where known, we discuss mechanisms of interference on specific assays and methodologies. We specifically address effects of commonly encountered Hbs, such as carbamyl-Hb, HbS, HbC, HbE, and HbF, on assays that use cation-exchange chromatography, immunoassays, or boronate affinity methods for measuring gHb.

Summary: A variety of patient- and laboratory-related factors can adversely affect the measurement of gHb in patients harboring Hb variants or derivatives. Identification of the variant or derivative Hb before or during testing may allow accurate measurement of gHb by the selection of a method unaffected by the given variant or derivative. However, laboratories should make available alternative, non-Hb-based methods for assessing long-term glycemic control in individuals with HbCC, HbSS, or HbSC disease, or with other underlying disorders where the concentration of gHb does not accurately reflect long-term glycemic control.

/pdf/effects-of-hemoglobin-variants-and-chemically-modified-31f6k684bx.pdf

Effects of Hemoglobin Variants and Chemically Modified Derivatives on Assays for Glycohemoglobin

Clostridium difficile is well recognized as the major, if not the only, important cause of infectious diarrhea that develops in patients after hospitalization in the United States, and likely, in developed countries around the world [1]. The temporal relation between the onset of C. difficile-associated diarrhea (CDAD) and prior or concurrent antimicrobial therapy has caused confusion regarding the pathogenesis of this disease and has led to consideration of this infection as distinct from

/pdf/clostridium-difficile-associated-diarrhea-diabeeg9js.pdf

Clostridium difficile--associated diarrhea.

Only 10%-20% of all cases of antibiotic-associated diarrhea (AAD) are caused by infection with Clostridium difficile. Other infectious organisms causing AAD include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species, and Salmonella species. Most of the clinically mild AAD cases are due to functional disturbances of intestinal carbohydrate or bile acid metabolism, to allergic and toxic effects of antibiotics on intestinal mucosa, or to pharmacological effects on motility. Saccharomyces boulardii and Enterococcus SF68 can reduce the risk of developing AAD. Patients receiving antibiotic treatment should avoid food containing high amounts of poorly absorbable carbohydrates. Mild cases of AAD that may or may not be caused by C. difficile can be resolved by discontinuation of antibiotic therapy and by dietary carbohydrate reduction. Only severe AAD caused by C. difficile requires specific antibiotic treatment.

https://www.jstor.org/stable/pdfplus/4481611.pdf

Mechanisms and Management of Antibiotic-Associated Diarrhea

https://www.gastrojournal.org/article/0016-5085(93)90290-S/pdf

Agenesis of the dorsal pancreas in a woman with diabetes mellitus and in both of her sons

Tumor necrosis factor-α (TNF-α) has been found to be elevated in patients during hemodialysis and is thought to mediate some of the immune and metabolic dysfunctions in these patients. It has been speculated that infusions of soluble TNF receptor (sTNF-R) may prevent some of the cytotoxic effects of TNF. However, little is still known about preexisting serum TNF-R levels in patients with chronic renal failure, with or without hemodialysis. Therefore we analyzed serum samples of sTNF-R in 26 patients with chronic renal failure (group I), 6I hemodialysis patients (group II), 9 renal transplant recipients with acute renal failure requiring posttransplant dialysis (group III), 13 renal transplant patients with rejection and moderate kidney dysfunction (group IV), and 21 renal transplant recipients with borderline kidney dysfunction and diverse infectious complications (group V). Control groups consisted of 34 blood donors and diseased controls (11 renal transplant recipients with normal kidney function without complications). All patient groups showed significantly higher sTNF-R levels compared to the control groups. In groups I, IV, and V comparable levels were observed. In group I there was a clear correlation between sTNF-R levels and serum creatinine. The highest sTNF-R serum levels were seen in groups II and III, but there was no correlation with creatinine. In the posttransplant cases (group III and diseased controls) there was a decrease in sTNF-R with improvement of kidney function. These data strongly suggest that sTNF-R serum levels are dependent on kidney function.

Serum levels of the soluble receptor for tumor necrosis factor in patients with renal disease.

Hb Sherwood Forest has been so far identified in only one patient in 1977. This study describes the second detection of this hemoglobin variant by routine high performance liquid chromatography (HPLC) in a diabetic patient and her healthy grand niece. In both, glycosylated hemoglobin (HbA 1c ) values were excessively elevated (52%), as determined by HPLC with a cation exchange column. The latex agglutination test showed values of HbA 1c in the expected normal range. Citrate agar electrophoresis revealed a hemoglobin variant with a mobility similar to HbF. Amino acid analysis and DNA sequence analysis revealed an Arg→Thr exchange at codon 104 of the β-chain. This sequence has been described as Hb Sherwood Forest in 1977. The hemoglobin variant is clinically silent and might be confused with excessively high HbA 1c in routine measurement of glycosylated hemoglobin

Hemoglobin Sherwood Forest detected by high performance liquid chromatography for hemoglobin A1c.

In 1917, spirochaetal neurosyphilis was treated successfully with malariotherapy in combination with salvarsan or bismuth. Malariotherapy for spirochaetal Lyme disease has been discussed, but the m...

E. C. Reisinger

Papers

Mechanisms and Management of Antibiotic-Associated Diarrhea

Agenesis of the dorsal pancreas in a woman with diabetes mellitus and in both of her sons

Serum levels of the soluble receptor for tumor necrosis factor in patients with renal disease.

Hemoglobin Sherwood Forest detected by high performance liquid chromatography for hemoglobin A1c.

Antibiotics and increased temperature against Borrelia burgdorferi in vitro