Daniel R. Hinthorn

Enteral nutrition in patients receiving mechanical ventilation: Multiple sources of tracheal colonization include the stomach

Nutritional therapy of patients receiving mechanical ventilation includes enteral feeding. To determine the frequency of gastric microbial colonization in patients receiving enteral nutrition, 18 patients with acute respiratory failure receiving ventilation were studied. Multiple sources of tracheal colonization were then evaluated to determine the frequency of tracheal transmission of gastric flora and the relationship of gastric colonization and transmission to nosocomial respiratory infection. The stomach was colonized in every patient who received enteral feeding. Tracheal colonization occurred in 89 percent (16 of 18) of patients. In 12 of these 16 patients, 14 organisms colonized the trachea after transmission from the stomach and/or oropharynx. Thirty-six percent (five of 14) of organisms transmitted to the trachea originated from the stomach, whereas another 36 percent (five of 14) were first recovered from the oropharynx. Four tracheally transmitted organisms were first recovered simultaneously from the stomach and oropharynx. Nosocomial respiratory infection developed in 11 patients (63 percent). Three infections occurred during the six-day study period, one of which was associated with transmission of a gastric organism. Multiple sources of tracheal colonization occur in patients receiving enteral nutrition. The stomach is an important source of tracheal colonization. Enteral nutrition can be associated with gastric flora colonizing the trachea and causing nosocomial respiratory infection.

pH-Dependent Accumulation of Clindamycin in a Polycystic Kidney

We determined the concentrations of clindamycin and gentamicin in fluid aspirated from 16 cysts of a surgically excised polycystic kidney. The patient had received both drugs intravenously for seven days before nephrectomy. The cysts were grouped into proximal (pH greater than 6.5) and distal (pH less than 6.5) types according to the pH of the fluid. In nine proximal cysts the mean concentration of gentamicin was 1.3 +/- 0.2 and that of clindamycin was 9.2 +/- 2.3 micrograms/mL. In seven distal cysts the gentamicin concentration was 0.7 +/- 0.2 micrograms/mL and the clindamycin concentration was 34.0 +/- 5.2 micrograms/mL. Plasma gentamicin was 3.8 (peak) and 1.9 (trough) micrograms/mL, and clindamycin was 3.9 micrograms/mL (random). Clindamycin cyst concentrations showed an inverse correlation with cyst fluid pH (r2 = 0.78). These studies confirm that in autosomal dominant polycystic kidney disease (ADPKD), certain cysts develop steep pH gradients between fluid and plasma and indicate that intracystic pH determines the extent to which basic lipophilic antibiotics accumulate in the fluid. Lipid-soluble antibiotics with relatively alkaline pKaS may be useful in the treatment of infected renal cysts.

Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy

BACKGROUND Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. METHODS Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. RESULTS The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. CONCLUSIONS Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors. CLINICAL TRIALS REGISTRATION NCT00031486.

Candidemia in patients with diabetes mellitus: epidemiology and predictors of mortality

Candidemia is the fourth most frequent nosocomial bloodstream infection in the US. The clinical characteristics and outcome of candidemia in adult patients with diabetes mellitus (DM) have not been reported in the literature. The objective of the study was to determine the epidemiology and determinants of mortality in diabetic patients with candidemia. A retrospective cohort study among diabetic patients with candidemia was carried out at 2 medical centers. The primary outcome was death from any cause after the onset of candidemia until discharge from the hospital. A stepwise logistic regression analysis was performed to determine the predictors of mortality. From June 1995 to June 2003, 87 patients with both DM and candidemia were studied. Candida albicans was the most common (48/87, 55%) and Candida glabrata the second most common isolate of candidemia (18/87, 21%). Overall hospital mortality was 39% (34/87). Logistic regression analysis identified 3 independent determinants of death; Apache II score≥23 (OR 8.3, 95% CI{2.7, 25.4}, p=0.0002), nosocomial candidemia (OR 10.2, 95% CI{1.1, 97.9}, p=0.04), and mechanical ventilation (OR 3.6, 95% CI{1.1, 11.2}, p=0.03). The study demonstrates the emergence of non-albicans species of Candida as major causes of candidemia among diabetic patients. The severity of illness reflected by Apache II was the most significant predictor of mortality among diabetic patients with candidemia.

Pharmacological Evaluation of Cefaclor in Volunteers

The plasma and urine concentrations of cefaclor were measured after oral administration of single and multiple doses to volunteers. Cefaclor was rapidly absorbed, rapidly excreted in the urine, well tolerated without toxicity, and failed to accumulate in the plasma with chronic dosing.

Use of clindamycin in patients with liver disease.

Hepatotoxicity has been noted by several investigators during parenteral use of clindamycin, and some have reported that drug half-life is prolonged in the presence of liver disease. We administered 300 mg of clindamycin intravenously at 12-h intervals for 2 days to patients with acute and chronic hepatitis, cirrhosis, and controls to determine whether clindamycin will exacerbate preexisting hepatic dysfunction or whether drug excretion will be delayed in patients with liver disease as compared with controls. Exacerbation of hepatotoxicity was not found in this study. There was a small, but significant, delay in drug elimination between cirrhotics and controls, even after the first dose of clindamycin (P < 0.05); however, half-lives in all categories were in the range usually considered normal. We conclude that clindamycin can be used in liver disease in some circumstances, if proper precautions are exercised.

Nonenterococcal Group D Streptococcal Septicemia: Association with Unrecognized Endocarditis

68 patients presented to the Veterans General Hospital, Taipei with nonenterococcal group D streptococcal septicemia in the years 1985-1987. 36 patients (53%) had nonenterococci as part of a polymicrobial bacteremia. The large intestine was not examined in most patients. Five patients (7%) had associated colonic carcinoma, and 17 patients (25%) had colorectal diseases. Only 7/68 patients (10%) were clinically diagnosed as having infective endocarditis by the doctors in charge. The others were regarded as having septicemia. The charts of these patients were reviewed retrospectively to diagnose infective endocarditis based on strict definitions. One (1%) had definite endocarditis proved at autopsy. 16 patients (24%) had probable endocarditis due to the presence of either a new regurgitant murmur or both a predisposing heart disease and embolic phenomena; 39 (57%) had possible endocarditis based on evidence of having either a predisposing heart disease or embolic phenomena; and only 12 (18%) had no evidence of endocarditis. 27 patients (40%) had at least one predisposing heart disease associated with endocarditis. 51 patients (75%) had at least one lesion suggesting embolic phenomena. 30 patients (44%) had electrocardiographic abnormalities. This high incidence of arrhythmia in nonenterococcal septicemia is of particular interest and could be related to cardiac involvement in some patients. The overall mortality, 62% (42/68), was extremely high in our series, but in those who were clinically diagnosed and treated as infective endocarditis, the mortality was low, 14% (1/7). We suggest all patients with nonenterococcal septicemia associated with either heart disease or lesions of CNS, lung, heart, kidney or limbs suggesting embolic phenomena should be regarded as having possible or probable endocarditis. Treating such patients as having infective endocarditis may reduce the mortality in nonenterococcal septicemia.

Eosinophilic Meningitis Due to Infection With Paragonimus kellicotti

Paragonimus kellicotti is an emerging pathogen in the United States with 19 previously reported cases, most in Missouri. Pulmonary symptoms with eosinophilia are most common, though 1 case did involve the central nervous system with few symptoms. We describe the first 2 cases of eosinophilic meningitis due to Paragonimus kellicotti.

Blindness in a Woman With Human Immunodeficiency Virus Infection and Syphilis

Background: A concomitant infection with human immunodeficiency virus (HIV) may alter the natural history of other infections. Several reports indicate that syphilis may behave more aggressively when HIV infection is present. Case: A woman presented with a rash involving her hands and feet and progressive loss of the vision in her right eye. Her serologic tests for syphilis and HIV infection were positive. A diagnosis of neurosyphilis was confirmed by an analysis of cerebrospinal fluid (CSF). She was treated with high-dose intravenous (IV) penicillin. Her skin lesions resolved, but her vision did not improve. Conclusion: The incidence of HIV infection among women is rising. A patient with HIV and syphilis may develop neurosyphilis in a much shorter time than a patient without HIV infection.