Extrinsic Contamination of Intravenous Infusates Administered to Hospitalized Children in Mexico.

Nosocomial bloodstream infection (BSI) is a significant cause of morbidity in hospitalized children, particularly among infants in neonatal intensive care units. Contamination of iv infusates is an unusual cause of nosocomial BSI, in part because high quality manufacturing standards and quality control have made intrinsic contamination (contamination during manufacture) extremely rare. 1 Studies examining the frequency of extrinsic contamination (contamination during preparation and administration) in the United States have demonstrated contamination rates of 0.6 to 2.5%. 2–5 However, in Mexico Macías-Hernández et al. 6 demonstrated an extrinsic contamination rate of 6.8% in iv infusates in a single hospital in the state of Guanajuato. Gram-negative rods of the tribe Klebsielleae were the most common contaminants. A subsequent survey in six hospitals in Guanajuato State found an overall contamination rate of 2.1% (range of rates in individual hospitals, 0 to 5.5%). 7 These data suggest that an endemic level of extrinsic contamination of iv infusates could exist in Mexican hospitals. The objective of this study was to examine the extent of iv infusate contamination in a broader geographic sample of public hospitals in Mexico. Methods. Study design and participating hospitals. A cross-sectional survey of extrinsic contamination of iv infusates administered to pediatric patients was conducted in eight hospitals in five states from June, 1997, to May, 1999. Invitations to participate in the study were made to over 20 institutions participating in a national network for infection control in pediatrics. The hospitals agreeing to participate included two general hospitals with pediatric units, five second level pediatric hospitals and one third level pediatric hospital. All of the hospitals are public teaching hospitals serving low income populations. Sample size and sampling strategy. A minimum sample size of 90 patients in each hospital was determined to represent the contamination rate for the entire group of hospitals, using a precision level of 10%, a power of 90% and an assumed contamination rate of 5%. Patients were selected randomly, using a selection interval and a random starting point. Infusate samples were obtained during 2 days per week, until the required number of samples had been collected. Hospitals required an average of 3 months to collect the required number of samples. Samples were drawn in all the wards of the hospital where pediatric patients were cared for, including pediatric and neonatal intensive care units, emergency, medical and surgical wards. None of the samples was drawn from total parenteral nutrition infusates. Staff nurses prepare the admixtures of iv infusates by medical indication for every patient, typically every 8 h. Premixed iv infusates in volumes smaller than 500 ml are not available at any of the participating hospitals. The tubing of the infusion delivery systems are typically changed at a maximum of 48 h, and the bottles or burettes are changed every 8 h shift up to a maximum of 24 h. The expiration date of the iv infusates is not recorded and unused admixed fluids are discarded at the end of the day. The name, age, ward, diagnosis, type of iv infusate and the presence of central venous catheter were recorded according to a standard format. The prevalence rate was calculated with 95% confidence intervals (95% CIs) around the point estimator with a binomial distribution. 8 Hypothesis testing was conducted by using the chi square test. Microbiologic methods. Trained nurses obtaining iv infusate samples washed their hands before drawing samples. The injection port of the infusion system was disinfected with 70% alcohol, and then samples of 0.5 to 1.0 ml of iv infusates were drawn through it by a previously described methodology. 6 We used 70% alcohol because it exhibits rapid broad spectrum antimicrobial activity against vegetative bacteria (including Mycobacterium), viruses and fungi. 9, 10 Samples were inoculated into either 5 ml of thioglycolate or brain-heart infusion broth and incubated at 37°C for 48 h. At 24 and 48 h each broth culture was inspected for turbidity. When turbidity was observed a Gram stain of the broth was performed and the broth was subcultured on sheep blood and eosin methylene blue agar plates. Colonies on subculture plates were identified at the species level by conventional biochemical techniques, with the exception of the coagulase-negative staphylococci, which were not characterized further. Results. A total of 1011 iv infusates were sampled, with an average of 126 samples (range, 93 to 172) taken at each of the 8 participating hospitals. There were 60 positive infusate cultures, resulting in an overall contamination rate of 5.9% (95% CI 4.6 to 7.6%). The contamination rate in individual hospitals ranged from 0.0 to 18.9% (Table 1). Newborn wards had a higher contamination rate than other clinical wards (14.4%vs. 4.0%, P < 0.0001). Overall 16.5% of the samples were obtained from newborns. Using Mantel-Haenszel analysis stratified by hospital, we found newborns to have 4 times higher risk of contaminated iv infusates than other age groups (odds ratio, 4.2; 95% CI 2.6 to 10.5). Only 22% of the sampled patients had a central venous catheter. There was a marginal statistically significant difference in the contamination rate between iv infusates containing 5 to 10% dextrose in water and those that included electrolytes that were admixed in the ward by staff nurses (4.7%vs. 7.4%, P = 0.07). However, the study was not designed to have enough power to make this distinction.Table 1: Infusate contamination rate and relative distribution of microorganisms isolatedGram-negative rods were isolated from 48 (80%) of the 60 positive cultures (Table 1). Klebsiella spp. and Enterobacter spp. accounted for 43 and 28% of the 48 Gram-negative isolates, respectively. Coagulase-negative staphylococci and Staphylococcus aureus accounted for 75 and 25% of the 16 Gram-positive isolates, respectively. Candida spp. were isolated from 5 (8.3%) cultures. One-half of the Klebsiella isolations were found in a single hospital, and 88% of the Enterobacter isolations were found in one other. Discussion. We evaluated the contamination rate of iv infusates in a random sample of pediatric patients in eight public hospitals in Mexico and found results consistent with two previous reports in Mexico. 6, 7 Collectively these surveys demonstrate a substantially higher extrinsic contamination rate than reported from the United States. 2–5 Gram-negative rods represent the vast majority of isolates in these Mexican studies, contrasting with Gram-positive cocci found in reports from the United States. There is almost no information about the size of the inoculum from the iv infusates and the likelihood of developing BSI. Molecular typing to correlate iv infusate contamination and bacteremia would eventually help to confirm or refute common source outbreaks. Our study design was cross-sectional and did not include any systematic follow-up to detect clinical outcomes. The original protocol requested blood be drawn for culture after the iv infusion was sampled. However, it proved expensive and all hospitals could not comply with this part of the protocol. Four hospitals (A, C, E and G) did obtain blood cultures after sampling the iv infusion and drew a total of 160 blood cultures. In 2 patients the same microorganism was cultured from the infusion and the bloodstream (Staphylococcus coagulase-negative and Klebsiella pneumoniae). A link between a contaminated iv infusion and bacteremia/sepsis has been documented during natural experiments and outbreak investigations. 11 Time since infusate contamination as well as dextrose concentrations are likely to influence bacterial growth. Maki and Martin 12 demonstrated that members of the tribe Klebsielleae have an impressive ability to proliferate in dextrose-containing iv fluids at room temperature. In Mexico Macías-Hernández et al. 6, 7 used qualitative and quantitative methods to demonstrate that contamination of iv infusates with Gram-negative organisms is virtually always massive. The small amount of infusate drawn for culture is sufficient to detect massive contamination, but it may be possible that low inoculum contamination would be not detected. None of the participating hospitals have premixed intravenous fluids available. This suggest that the wide differences in contamination rates among hospitals are more likely related to the handling of iv infusates and also might be explained by differences in the quality of practices, staffing levels and the available material resources. The high contamination rates at hospital B and hospital D were due to frequent isolation of Enterobacter spp. and Klebsiella spp., respectively. This result implicates point sources of extrinsic contamination of iv infusates more strongly than contamination of the exterior surface of the port. Contamination during the sampling procedure is a less likely explanation of our results for two reasons: (1) it would have more likely been reflected as a mixture of isolates and have included more Gram-positive isolates; (2) we used alcohol (70%) to disinfect the exterior surface of the port before obtaining the sample, which is a highly effective and widely used procedure for disinfection of iv tubing ports. Commercial preparations of IV fluids in small amounts (100 or 200 ml) are not available among public hospitals in Mexico. Consequently admixture of iv infusates without the use of a biosafety cabinet is a commonly performed task by the nurses at all the participant hospitals. Rather than using premixed dextrose and electrolyte solutions, most pediatricians prescribe individualized solutions for every patient every day. This requires nurses to mix and handle these fluids from several multidose vials in a burette for administration to hospitalized infants, typically from bottles of 1000 ml of dextrose in water or saline solution. The higher contamination rate of iv infusates that we found among neonates receiving iv fluids might be explained by a greater manipulation involved in the preparation of small volumes of iv infusates. Health care workers’ hands may play a critical role in the contamination and potentially in the spread of microorganisms causing clusters of contaminated iv infusates, with high endemic levels of contamination (especially if there are systematic errors in the processes) and nosocomial outbreaks from a common source. In fact during our survey we found clusters of microorganisms (Enterobacter spp., Klebsiella spp. and coagulase-negative staphylococci) identified in particular hospitals, which might have represented individually a point source of contamination. These styles of practice and a low compliance with hand washing in the clinical services reflect poor standards of medical care. To prevent extrinsic contamination of iv infusates in Mexico, we advocate a rational prescription and a critical assessment of each child receiving iv infusates. The use of premixed iv infusates manufactured in small volumes for newborns and infants is sterile and by requiring minimal manipulation would decrease the probability of extrinsic contamination. If additional admixture is necessary only trained personnel should perform it, with adherence to strict sterile aseptic technique. The admixture of iv fluids should be limited to a central area such as the hospital pharmacy, using a biologic safety cabinet. 13 The Ministry of Health should promote the manufacturing, commercialization and wide availability of premixed iv infusates in small volumes for use in pediatrics. Acknowledgments. Supported in part by a grant from the Thrasher Research Fund. We are grateful to Dr. Daniel Romero from Hospital Pediátrico Moctezuma, Dr. Mauricio Rivera from Hospital Pediátrico Legaria, and Dr. Ramón Camacho Delgado from Hospital Infantil de Morelia for their valuable collaboration in data collection. We especially thank Dr. Charles Huskins for his review and comments regarding the manuscript.