Charles D. Ericsson

Central Venous Catheters Coated with Minocycline and Rifampin for the Prevention of Catheter-Related Colonization and Bloodstream Infections: A Randomized, Double-Blind Trial

See related articles on pp 257-266 and 275-280 and editorial comment on pp 304-306. Central venous catheters are indispensable in the treatment of critically and chronically ill patients, but they are the leading cause of primary nosocomial bloodstream infection [1, 2]. A study of hospitals in the National Nosocomial Infection Surveillance System, conducted between 1986 and 1990, showed that rates of bloodstream infection were substantially higher in patients who were in intensive care units and had intravascular devices than in those who did not have such devices [3]. To decrease the risk for catheter colonization and infection, antiseptic and antibiotic agents have been applied topically at the insertion site [4-6]. More recently, the use of antimicrobial flush solutions has been proposed [7]. However, coating venous catheters with antiseptic or antimicrobial agents may have an even more pronounced protective effect against colonization and infection, particularly if both the external and internal surfaces of the device are coated. Since 1990, several types of antiseptic or antimicrobial vascular catheter coatings have been developed and studied [8, 9]. Maki and colleagues [9] investigated central venous catheters coated with chlorhexidine-silver sulfadiazine; the coated catheters seemed less likely than the uncoated catheters to be associated with bloodstream infections. We recently coated vascular catheters with a combination of minocycline and rifampin after treatment with the tridodecylmethyl-ammonium chloride surfactant. In vitro, these catheters were shown to have broad-spectrum antimicrobial inhibitory activity that was significantly superior to the activity of catheters coated with chlorhexidine-silver sulfadiazine [10, 11]. The catheters coated with minocycline and rifampin were also found to be highly efficacious in preventing catheter colonization and subcutaneous infection in a rabbit model [11]. In a double-blind, randomized clinical trial, we studied the efficacy of catheters that were treated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin in preventing catheter colonization and bloodstream infection in hospitalized patients. Methods Study Sample Our study was conducted simultaneously at five university-based hospitals in the Texas Medical Center in Houston: The University of Texas M.D. Anderson Cancer Center (518 beds), Veterans Administration Medical Center (1050 beds), Hermann Hospital (600 beds), Ben Taub General Hospital (580 beds), and The Methodist Hospital (904 beds). The study began on 1 September 1994 and ended on 27 March 1995. Hospitalized patients 18 years of age or older who required a triple-lumen polyurethane central venous catheter at a new insertion site were asked to participate. We excluded pregnant women, patients who were allergic to rifampin or tetracycline, patients with dermatitis or a burn over the insertion site, and patients for whom the anticipated duration of catheterization was less than 3 days. All patients gave informed consent. Randomization All catheters were triple-lumen, polyurethane, 7 French, and 20 cm long (Cook Critical Care, Bloomington, Indiana). The coated catheters were pretreated with tridodecylmethyl-ammonium chloride and then coated, 18 hours later, with minocycline and rifampin. The levels of minocycline and rifampin on the external and internal surfaces of coated catheters before insertion, as determined by high-performance liquid chromatography, were 139.3 g/cm and 13.9 g/cm, respectively. Control catheters were untreated and uncoated. All catheters were gas sterilized and placed in identical trays, and each tray was assigned an identification number. The trays were then randomly assigned into blocks of six: three with coated catheters and three with control catheters. Each block of trays was placed in boxes by Cook Critical Care, and the boxes were shipped to the five hospitals. When a patient was determined to be eligible, a tray was removed from the box (trays were removed one at a time, in sequential order from top to bottom), and that catheter was used for the patient. The catheter identification number was recorded on a data entry form and on the patients medical chart; neither the patient nor the clinician who inserted the device knew which catheter (coated or uncoated) had been used. Catheter Insertion and Care Study catheters were inserted into the subclavian vein, internal jugular vein, or femoral vein of patients who had no other indwelling catheter. Study catheters were not exchanged over guidewires. Maximal sterile barrier precautions were taken, including use of a sterile gown, sterile gloves, full sterile drapes, a mask, and a cap. At the time of catheter insertion and at each dressing change, the insertion site was cleaned with chlorhexidine gluconate (at The Methodist Hospital) or 10% povidone-iodine scrub (at all other hospitals). In each case, the preparation was applied to the skin for 2 minutes before catheter insertion. The insertion site was then covered with sterile gauze and taped securely. The insertion site was inspected every 72 hours (during a dressing change) for evidence of infection, such as erythema, purulence, swelling, or tenderness over the catheter. During follow-up, the following information was obtained for all patients: site of catheter insertion; dates of catheter placement and removal; occurrence of difficulties and violations of aseptic technique during insertion or removal, if any; reason for using the catheter (chemotherapy, total parenteral nutrition, administration of blood products, or a combination of these reasons); type of dressing; and reason for catheter removal. In addition, clinical data were obtained on underlying disease, neutrophil and platelet counts, antibiotic therapy administration, other therapeutic interventions administered during the period of catheterization, and the presence or absence of fever and infection during catheterization. The catheter remained in place until it was no longer needed; until a specific event, such as catheter-related infection, necessitated its removal; or for 28 days, whichever occurred first. Microbiological Methods Quantitative Cultures of Central Venous Catheters The entire catheter was removed aseptically, and 4-cm segments were cut from the catheter tip and the subcutaneous section. These segments were semiquantitatively cultured by using the roll-plate method; the same segment was then quantitatively cultured by using the sonication method [12-14]. Organisms recovered by either method were fully identified according to standard microbiological methods. Coagulase-negative staphylococci were classified as gram-positive cocci in clusters that produced catalase but not coagulase and were categorized according to species by using the Staph-Ident System (Analytab Products, Plainview, New Jersey). All hospitals used the same methods for culture. Skin Cultures To determine whether bacteria became resistant to the antibiotics that coated the study catheters, skin samples obtained from the insertion site were cultured at the time of insertion and within 24 hours after catheter removal, as described elsewhere [15]. Organisms recovered from the insertion site were fully identified by using standard microbiological methods. Antimicrobial Resistance We used the modified Kirby-Bauer technique to test the antimicrobial activity of the catheters coated with minocycline and rifampin against all organisms isolated from indwelling coated catheters at the time of catheter removal [16]. The zones of inhibition against staphylococci cultured from coated catheters were compared with those of uncoated catheters. The minimal inhibitory concentration (MIC) of minocycline hydrochloride (Lederle Laboratories, Pearl River, New York) and rifampin (Ciba-Geigy Corp., Summit, New Jersey) against staphylococcal organisms that colonized the catheter tip, subcutaneous segments, and adjacent skin insertion sites of the coated catheters was determined. A microbroth dilution method was used to determine the MIC in accordance with guidelines established by the National Committee for Clinical Laboratory Standards [17]. Definitions The definitions adopted for our study were proposed by the Centers for Disease Control and Prevention [18]. Colonization of a central venous catheter was defined as 1) the isolation from either the tip or the subcutaneous segment of 15 or more colony-forming units of any organism by the rollplate technique or 2) isolation of more than 1000 colony-forming units of any organism by the sonication technique. Catheter-related bloodstream infection was defined as the isolation of microorganisms from the bloodstream (blood was obtained through venipuncture, not through the catheter) of a patient who had concurrent clinical manifestations of sepsis and no source for the bloodstream infection other than the vascular catheter. In addition, the catheter had to be colonized with the same organism (same species and same antibiogram). To confirm the diagnosis of catheter-related bloodstream infection, DNA molecular typing done using pulse-field gel electrophoresis was performed on organisms that were of the same species, had the same antibiogram, and were isolated from the catheter and blood during the period of catheterization. Patients were considered to have fever if the oral body temperature was greater than 38 C. Neutropenia was defined as a polymorphonuclear count of fewer than 1000 cells/mm3. Thrombocytopenia was defined as a platelet count of fewer than 100 000 cells/mm3. Molecular Typing Molecular typing was performed by using pulse-field gel electrophoresis. Identical organisms with similar DNA profiles that were isolated from a segment of the colonized catheter and from the bloodstream confirmed the diagnosis of catheter-related bloodstream infection. However, a mismatch did not rule out such a diagnosis because catheter coloniza

Enteroaggregative Escherichia coli as a Major Etiologic Agent in Traveler's Diarrhea in 3 Regions of the World

Enteroaggregative Escherichia coli (EAEC) has been reported to cause travelers diarrhea and persistent diarrhea in children in developing countries and in immunocompromised patients. To clarify the prevalence of EAEC in travelers diarrhea, we studied 636 US, Canadian, or European travelers with diarrhea: 218 in Guadalajara, Mexico (June--August 1997 and 1998), 125 in Ocho Rios, Jamaica (September 1997--May 1998), and 293 in Goa, India (January 1997--April 1997 and October 1997--February 1998). Stool samples were tested for conventional enteropathogens. EAEC strains were identified by use of the HEp-2 assay. EAEC was isolated in 26% of cases of travelers diarrhea (ranging from 19% in Goa to 33% in Guadalajara) and was second only to enterotoxigenic E. coli as the most common enteropathogen in all areas. Identification of EAEC reduced the number of cases for which the pathogen was unknown from 327 (51%) to 237 (37%) and explained 28% of cases with unknown etiology. EAEC was a major cause of travelers diarrhea in 3 geographically distinct study areas.

The Practice of Travel Medicine: Guidelines by the Infectious Diseases Society of America

David R. Hill, Charles D. Ericsson, Richard D. Pearson, Jay S. Keystone, David O. Freedman, Phyllis E. Kozarsky, Herbert L. DuPont, Frank J. Bia, Philip R. Fischer, and Edward T. Ryan National Travel Health Network and Centre and Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, England; Department of Medicine, University of Toronto, and Center for Travel and Tropical Medicine, Toronto General Hospital, Toronto, Ontario, Canada; Department of Internal Medicine, Clinical Infectious Diseases, University of Texas Medical School at Houston, Department of Internal Medicine, St. Luke’s Hospital, and Center for Infectious Diseases, University of Texas at Houston School of Public Health, and Department of Medicine, Baylor College of Medicine, Houston, Texas; Departments of Medicine and Pathology, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia; Departments of Medicine and Epidemiology, Division of Geographic Medicine, University of Alabama at Birmingham, Birmingham; Department of Medicine, Infectious Diseases, Emory University School of Medicine, and 16 Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia; Department of Medicine and Laboratory Medicine, Yale Medical School, New Haven, Connecticut; Department of Pediatrics, Division of General Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, and Mayo Eugenio Litta Children’s Hospital, Mayo Clinic, Rochester, Minnesota; and Department of Medicine, Division of Infectious Diseases, Harvard Medical School, Harvard School of Public Health, and Tropical and Geographic Medicine Center, Massachusetts General Hospital, Boston, Massachusetts

Therapy of travelers’ diarrhea with rifaximin on various continents

OBJECTIVE:Our aim was to compare the efficacy and safety of rifaximin, a virtually nonabsorbed antibiotic, 600 and 1200 mg per day, with placebo in patients with travelers’ diarrhea.METHODS:This was a multicenter, 1:1:1 randomized, parallel-group, double-blind study, conducted in Antigua, Guatemala; Guadalajara and Morelia, Mexico; and the coast of Kenya north and south of Mombasa. Adult patients with acute travelers’ diarrhea were recruited; exclusion criteria included primarily medication that could influence the outcome. Subjects were treated for 3 days, three times daily; follow-up lasted 5 days. For each 24-h period, the subjects completed a diary card. Pre- and posttreatment stool, blood, and urine samples were assessed.RESULTS:Among the 380 volunteers, median time to the last unformed stool was 32.5 and 32.9 h in both rifaximin groups, compared with 60.0 h with placebo (p = 0.0001). Also, secondary clinical outcome measures were favorably influenced by the active agent. No relevant side effects were reported.CONCLUSION:Rifaximin is efficacious and safe for treatment of travelers’ diarrhea at daily doses of 600 mg or higher.

Japanese Encephalitis Vaccine for Travelers: Exploring the Limits of Risk

The prevention of Japanese encephalitis in travelers presents the juxtaposition of 4 factors: a disease that is widespread throughout Asia, a disease with a low incidence in travelers, a vaccine about which there are safety concerns, and a clinical course that can result in death or permanent disability in two-thirds of symptomatic cases. Travel medicine practitioners often seem to be polarized into 2 groups: a group that gives more weight to the severity of the disease (and therefore often recommend vaccination) and another group that is more persuaded by the low occurrence of cases in travelers (and therefore rarely recommend vaccination). This review assesses the known risks of contracting Japanese encephalitis and the risks associated with the vaccine and tries to develop an appropriate way to recommend this vaccine to travelers who may be at significant risk.

Rifaximin: a nonabsorbed antimicrobial in the therapy of travelers' diarrhea.

Background/Aims: Bacterial enteropathogens, the major cause of travelers’ diarrhea, are customarily treated with antibacterial drugs. Rifaximin, a nonabsorbed antimicrobial was examined as treatment for travelers’ diarrhea. Methods: A randomized, prospective, double-blind clinical trial was carried out in 72 US adults in Mexico. Patients with acute diarrhea received one of three doses of rifaximin (200, 400 and 600 mg t.i.d.) or trimethoprim/sulfamethoxazole (TMP/SMX, 160 mg/800 mg b.i.d.) for 5 days. Results were compared with data from 2 placebo-treated historical control populations. Results: The shortest duration of treated diarrhea was seen in the group receiving 200 mg rifaximin t.i.d (NS). Clinical failure to respond to treatment occurred in 6 of 55 (11%) rifaximin-treated subjects versus 5 of 17 (29%) of TMP/SMX-treated subjects (NS). Sixteen of twenty (80%) of the enteropathogens isolated from the rifaximin-treated subjects and 7 of 7 (100%) from the TMP/SMX group were eradicated by treatment (NS). Sixteen of twenty-four (67%) enteropathogens identified were susceptible to TMP and all 24 were inhibited by ≤50 µg/ml of rifaximin. Rifaximin reduced the number of unformed stools passed during the first 24 h of treatment when compared with 2 control placebo groups (3.3 versus 5.1; p = 0.008 and 0.0001) and led to a reduced duration of post-enrollment diarrhea (mean values of 43.1 versus 68.1 and 81.9 h; p = 0.001). Conclusions: Rifaximin shortened the duration of travelers’ diarrhea compared with TMP/SMX and 2 earlier studied placebo-treated groups. A poorly absorbed drug if effective in treating bacterial diarrhea has pharmacologic and safety advantages over the existing drugs.

Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents.

Fecal specimens from individuals traveling to Mexico were examined before, during, and after travel for the presence of Escherichia coli resistant to ampicillin, chloramphenicol, gentamicin, kanamycin, streptomycin, sulfonamides, trimethoprim (TMP), and TMP-sulfamethoxazole (TMP-SMX). None of these individuals took prophylactic antibiotics, although 4 of 13 took short courses of an antimicrobial agent for therapy of travelers diarrhea. With an average of 9.3 E. coli per sample, resistance to all agents tested except gentamicin was shown to increase during the time in Mexico (P less than 0.001 to P less than 0.05). For example, no TMP-resistant (Tmpr) E. coli isolates were found by this method before travel, whereas 57% of the individuals had Tmpr and Tmpr-Smxr E. coli by the final week in Mexico. This increase in resistance occurred regardless of whether an individual took a short course of antimicrobial therapy. This study shows that travel itself, even without the use of prophylactic or therapeutic antimicrobial agents, is associated with the acquisition of resistant E. coli. Travel to developing nations may rival other sources of resistant organisms.

Successful treatment of vancomycin-resistant enterococcus faecium meningitis with linezolid: Case report and literature review

Vancomycin-resistant enterococci (VRE) are a rare cause of meningitis, occurring primarily in patients who have undergone neurosurgical procedures. We describe the first reported case of VRE meningitis successfully treated with linezolid. A 56-y-old female with subarachnoid hemorrhage underwent ventriculostomy and embolization of cerebral aneurysms. Her postoperative course was complicated by multiple infections needing repeated antibiotic courses, culminating in the development of VRE meningitis. She was treated with 600 mg of i.v. linezolid (MIC < 0.75 microg/ml) every 12 h for 6 weeks. After the fourth dose, peak and trough linezolid concentrations were 11.45 and 0.14 microg/ml in serum and 3.19 and 2.39 microg/ml in cerebral spinal fluid (CSF). On Day 19 of linezolid therapy, serum and CSF trough concentrations were 1.53 and 2.98 microg/ml, respectively. Linezolid achieved sufficient CSF concentrations to bring about clinical and bacteriological cure. We conclude that i.v. linezolid may be a useful option for treating VRE meningitis. We also present findings of a literature review, which identified 11 cases of VRE meningitis treated with other pharmacologic agents with mixed success.

Enteric Pathogens in Mexican Sauces of Popular Restaurants in Guadalajara, Mexico, and Houston, Texas

Context Travelers diarrhea is a foodborne illness. Identification of potentially contaminated food types can help physicians counsel patients. Contribution These investigators tested Mexican-style condiment sauces from 36 restaurants in Guadalajara, Mexico, and from 12 restaurants in Houston, Texas. Escherichia coli was present in 47 of 71 sauces from Guadalajara and 10 of 25 sauces from Houston. Enterotoxigenic E. coli was present in 4 of 43 tested sauces from Guadalajara; enteroaggregative E. coli was present in 14 of 32 tested sauces from Guadalajara. None of the Houston sauces contained enteropathogenic E. coli. Implications Restaurant condiment sauces are a potential source of E. coli enteropathogens in Guadalajara. The Editors Travelers diarrhea is the main health problem in international tourism in terms of frequency and economic impact (1). We previously found that among cases of travelers diarrhea with known causes, approximately 80% were caused by bacterial enteropathogens (2, 3). Contaminated food was the major vehicle of transmission of these infections (4-6). We studied Mexican sauces in Guadalajara, Jalisco, Mexico, to determine levels of Escherichia coli contamination and the presence of enteropathogens. We also studied a comparison group of similar sauces from Mexican-food restaurants in Houston, Texas. Methods We studied the level of contamination of tabletop sauces because they are a typical food found in most restaurants in Mexico and are commonly consumed by international tourists. We collected samples of Mexican saucespopularly known in the United States as green sauces, guacamole, pico de gallo, and red saucesfrom restaurants in the summer of 1998. We tested 71 sauces from 36 independently owned Mexican-style restaurants in Guadalajara that are known to be popular among U.S. travelers. We also studied a comparison sample of 25 similar sauces from 12 popular Mexican-style nonchain restaurants in Houston, Texas. For the Houston sample, we arbitrarily decided to include approximately one third of the number of samples and restaurants studied in Guadalajara. A well-mixed tablespoon-size (approximately 15 mL) sample of each type of sauce was collected from each restaurant in sterile containers. The samples were efficiently transported to our laboratories in Guadalajara or in Houston and were processed by trained personnel who followed the same standard procedures. The temperature of the sauces was not recorded. If the sample was collected in the evening, it was refrigerated at 4 C overnight and processed the next morning. The samples were diluted in sterile distilled water at a ratio of 1 to 10 and were placed in sterile Whirl-Pak bags (American Scientific Products, Houston, Texas) for homogenization in a Stomacher 400 blender (Dynatech Laboratories, Alexandria, Virginia). The pH of the food samples was determined by using a laboratory pH meter (Dynatech Laboratories). Enteric pathogens were identified from the sauces according to published methods (7). Five E. colilike colonies were retrieved from MacConkey agar plates of each food sample, stored in peptone media, and transported to our laboratory in Houston, where they were tested for the presence of enterotoxigenic E. coli by DNA hybridization and for enteroaggregative E. coli by HEp-2 adherence assay. The level of E. coli contamination was determined by placing serial twofold dilutions of food suspensions in 4-methylum-belliferyl--D-glucoronide medium plates. This method has proven to be as efficacious as and faster than conventional microbiological techniques (8, 9). Escherichia coli was chosen as an indicator of fecal contamination because it is more specific than measurements of total fecal coliforms (8, 9). Significant differences between groups were assessed by using the Fisher exact test to compare prevalence and the Wilcoxon rank-sum test to compare medians of sauce contamination in the two locations. We defined statistical significance as a P value less than 0.05. Discretionary funds from the University of TexasHouston Medical School were used to support the collection and analysis of the data. Results All samples were collected from sauce containers noted to be sitting on the tables at room temperature when we arrived at the restaurants in Guadalajara. In Houston, all of the sauces were brought to the tables on our arrival, and we noted that they were cold to the touch. Of the 96 samples of Mexican sauce that we studied, all tested negative for nonE. coli enteropathogens. Forty-seven (66%) of the 71 samples from Guadalajara grew E. coli, with a median count of 1000 E. coli colony-forming units (CFUs) per gram of sauce (range, 0 to 80 000 CFU/g). Of the 25 sauce samples from Houston, 10 (40%) grew E. coli, with a median of 0.0 CFU/g. We found a significant difference between sauces from the two cities when we compared the percentage of samples contaminated with E. coli (P = 0.03) and the median amount of E. coli colonies per sample (P = 0.008) (Table). The number of samples with E. coli contamination, as well as the median and total CFUs per gram of E. coli, were consistently higher in the samples from Guadalajara compared with Houston. Table. Presence of Escherichia coli in Tabletop Sauces from Public Mexican-Style Restaurants in Guadalajara, Mexico, and Houston, Texas Guacamole was the most frequently contaminated sauce tested in both cities; all three samples in Guadalajara and three of four samples in Houston tested positive for E. coli. The level of contamination of the guacamole sauces was higher in the Guadalajara samples than in the Houston samples (median, 4000 CFU/g vs. 10 CFU/g; P = 0.029). Moreover, among the sauces from Guadalajara restaurants, we found that the type of sauce containing the highest level of contamination was pico de gallo (median among all pico de gallo samples, 10 000 CFU/g), followed by guacamole (median, 4000 CFU/g) and green sauce (median, 1000 CFU/g). The samples of red sauce contained the lowest levels of contamination (median, 100 CFU/g). For each type of sauce studied, the Houston samples had lower median counts of E. coli, ranging from 0.0 CFU/g to 10 CFU/g. Of the 47 E. colicontaminated sauces from Guadalajara, 43 were available to be tested for enterotoxigenic E. coli and 32 were available for enteroaggregative testing. Enterotoxigenic E. coli was identified in 4 (9%) of the sauces, and enteroaggregative E. coli was found in 14 sauce samples (44%). All contaminated samples from Houston were tested for diarrheogenic E. coli strains, and neither enterotoxigenic E. coli (P = 0.128) nor enteroaggregative E. coli (P = 0.002) was identified. The average pH of all sauces from Guadalajara was 4.6 (range, 3.6 to 6.3), compared with 4.9 (range, 3.2 to 6.5) for the Houston sauces (P > 0.05). Discussion Travelers diarrhea is mainly a foodborne illness (4-6). We studied samples of sauces from popular restaurants in a tourist-oriented cityGuadalajara, Mexicowhere rates of travelers diarrhea are known to be high [2, 3]. Our study has several unique features: 1) We tested a specific and popular kind of food [Mexican sauces] from a group of nonchain restaurants that were open to the public, and 2) we compared the level of contamination of Mexican sauces from a city (Guadalajara) in a developing country with that of similar sauces from a city (Houston) in a developed country. We used this commonly consumed food item as a marker of fecal contamination. In our study, the Mexican sauces from Guadalajara more frequently contained fecal contaminants, and the median level of contamination (as measured by E. coli colonies per gram of sauce) was more than 1000 times greater than that of the sauces from Houston. We have previously shown frequent enteropathogen contamination of food samples in Guadalajara (6). We found enterotoxigenic and enteroaggregative E. coli, currently the major causes of diarrhea in travelers visiting Guadalajara (2, 3), in the sauces studied. Thus, these foods may play a role in the acquisition of illness. We previously reported a high prevalence of enterotoxigenic E. coli in cases of travelers diarrhea and the isolation of enterotoxigenic E. coli in food samples in Guadalajara (4-6). Although the presence of enterotoxigenic E. coli in food served in Mexico has been reported previously, this is one of the first descriptions of enteroaggregative E. coli contamination of such food. Enteroaggregative E. coli is a newly recognized pathogen in the group of diarrheogenic E. coli (3, 10). Its pathogenic role has been confirmed in outbreaks and in volunteer studies (11), and recent studies by our group have shown that enteroaggregative E. coli is nearly as important as enterotoxigenic E. coli in causing travelers diarrhea in Guadalajara (3). The prevalence of enteroaggregative E. coli in Mexican sauces may provide valuable information about the source of symptomatic and asymptomatic enteroaggregative E. coli infection in U.S. students visiting Guadalajara (12). It is a popular notion that low pH protects against bacterial food contamination. However, our results suggest that pH is an ineffective deterrent to microbial contamination because E. coli contamination was found in sauces with acidic pH levels. This finding could be explained by the recently described capacity of some E. coli strains to adapt to acidic conditions (13, 14). The higher level of E. coli contamination in the sauces in Guadalajara could be explained by the amount of time that sauces were kept at room temperature. We noted that the sauces in Guadalajara were prepared on the premises and were not refrigerated before or between meals, while the Houston sauces were refrigerated before they were served to customers. Moreover, we believe that the sauces were more likely to be handled by multiple workers and patrons (reuse of the same sauce) in Mexico than in Houston. Further studies of food hygiene practices are needed to clarify

Lack of emergence of resistant fecal flora during successful prophylaxis of traveler's diarrhea with norfloxacin.

Norfloxacin, a new quinolone carboxylic acid derivative, was compared with an identical-appearing placebo preparation in a prospective, randomized, double-blind trial for prevention of travelers diarrhea among 120 U.S. students arriving in Mexico. Prophylaxis was continued for 2 weeks. Diarrhea was defined as four unformed stools in 24 h plus an additional symptom of enteric disease. In the norfloxacin prophylaxis group, 4 of 56 subjects (7%) experienced diarrhea, compared with 36 of 59 subjects (61%) in the placebo group. The difference was significant (P less than 0.0001). In contrast to our previous experience with use of trimethoprim-sulfamethoxazole to prevent travelers diarrhea, quantitative stool cultures in the norfloxacin-treated group revealed a significant decline of normal aerobic fecal flora during prophylaxis (P less than 0.0005). Among stool samples from norfloxacin-treated subjects, 32 of 38 (84%) cultured on day 7 and 34 of 37 (92%) cultured on day 14 had no gram-negative bacilli. After norfloxacin was discontinued, fecal flora returned to pretreatment levels. No gram-negative aerobic flora resistant to norfloxacin were found during weekly quantitative cultures before, during, or after therapy.