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ORIGINAL CONTRIBUTIONS

Received: August 28^th 2014

Accepted: September 10^th 2015

Antimicrobial resistance trends in pathogens isolated from nosocomial infections

Héctor A. Rincón-León,^a Karla R. Navarro-Fuentes^b

^aCoordinación Delegacional de Investigación, Instituto Mexicano del Seguro Social

^bServicio de Epidemiología, Unidad de Medicina Familiar 11, Delegación Estatal en Chiapas, Instituto Mexicano del Seguro Social

Tapachula, Chiapas, México

Communication with: Héctor Armando Rincón-León

Thelephone: (962) 625 6158, celular (962) 107 7170

Correos electrónicos: hector.rinconl@imss.gob.mx; hrincon@hotmail.com

Background: The treatment of nosocomial infections is hindered by the increasing antimicrobial resistance pattern of germs that cause them. The objective was to assess trends in resistance of bacteria isolated from nosocomial infections.

Methods: Retrospective study from 2009 to 2012 on a third level hospital in Chiapas.

Results: 1300 germs were obtained, 62.3 % Gram negative bacteria, 22.8 % Gram positive and 14.9 % yeasts; imipenem resistance of P. aeruginosa went from 47.1 to 60.5 %, E. coli showed an increased resistance to aztreonam, cefepime and ceftazidime, A. baumannii increased resistance to amikacin, cefepime, ceftazidime and ciprofloxacin. Klebsiella pneumoniae decreased its resistance to amikacin and piperacillin/tazobactam; vancomycin resistance ranges from 3.6 to 25.5 %.

Conclusions: Gram negative organisms predominated, showing increasing trends in antimicrobial resistance. There was a proportional increase in the incidence of infection from E. coli, C. tropicalis and S. haemolyticus. It is essential to have programs and plans for the rational and evidence-based use of antimicrobials, as well as dissemination and adherence to clinical practice guidelines and the implementation of innovative programs for the prevention and control of nosocomial infections, isolation techniques and general care.

Keywords: Cross infection; Microbial drug resistance; Epidemiological surveillance; Infection control.

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Nosocomial infections are one of the greatest challenges for modern hospitals, as they are among the leading causes of death, increased morbidity, and disability in hospitalized patients.^1,2 They also cause an increase in the days of stay, in the direct and indirect costs of health care (lost working days), and morbidity of service providers;³ their management is extremely complex because they are secondary infections caused by bacteria that are highly resistant to antimicrobials.^4,5 For this reason, their monitoring and control require specialized personnel and programs designed specifically for the environment and the specific characteristics of each institution.¹

The most frequent nosocomial infections are of the urinary tract, surgical wound, lower respiratory tract, and the insertion site of intravenous catheters, with variations depending on the conditions and profile of each hospital;⁶ nosocomial infections can be caused by many bacteria, viruses, fungi, and parasites, which can be contracted by contact with another person in the hospital (cross-infection) or by the patient's own flora (endogenous infection); they can also be transmitted by an inanimate object or by newly contaminated substances from another human source of infection (environmental infection).⁴ 

As a result of extensive and, in most cases, improper use of antimicrobials, nosocomial pathogens are no longer easily-treated microorganisms, they are now highly resistant, which is a problem of great importance for the prevention and control of nosocomial infections,^7,8 especially at this time of scarce development of new antimicrobial drugs, with an even more pronounced and serious trend in the case of Gram-negative bacteria.^9-11 Specific surveillance studies on the type of pathogen and antimicrobial resistance patterns can optimize treatment and decrease mortality.^12,13 In Chiapas, Mexico, broad-spectrum antimicrobials are frequently used in in second- and third-level hospitals, without data on antibiotic resistance. The present study was developed to evaluate the antimicrobial resistance patterns of nosocomial infection-causing germs, and its trends over four years in a third-level hospital setting.

Methods

A retrospective cohort study was performed from September 2009 to December 2012 at Hospital Regional de Alta Especialidad Ciudad Salud (HRAECS) belonging to the Centro Regional de Alta Especialidad de Chiapas, of the Secretaría de Salud of Mexico. This hospital, located in the city of Tapachula, in the state of Chiapas in southeastern Mexico, is a tertiary care hospital with 90 beds, with an intensive care unit (ICU) with 12 beds and a wide variety of medical specialties and subspecialties. During the study period on average 2100 patients were admitted and discharged annually. All isolates of microorganisms classified as causing nosocomial infections in the inpatient and ICU areas were used for the study; those not classified as nosocomial infections were excluded. 

The program for prevention and control of nosocomial infections is carried out in the HRAECS according to the "Protocol for monitoring and control of nosocomial infections," which is based on the text Prevention of Nosocomial Infections, Practice guide, second edition (2003), of the World Health Organization (WHO).⁴ Any patient who entered the hospital was assessed by a nurse from the epidemiological surveillance program; cultures were requested if the patient had any invasive or high-risk device or procedure such as central venous or peripheral catheter, urinary catheter, surgical drainage, endotracheal catheter for mechanical ventilation, tracheostomy catheter, ulcers or sores on the skin, recent surgical wound, etc. This was done in order to assess whether the patient had an infection at admission, in order to dismiss it as a nosocomial infection. Each patient was visited daily during their hospital stay, and vital sign records were reviewed to document spiking fevers or signs of infection. The patient or relatives and the nursing staff caring for the patient were interviewed. In the case of some sign of infection, cultures were taken to assess nosocomial infection, and a daily census was developed to record this for every patient, along with days of stay, surgical and invasive procedures performed, nosocomial infection diagnosed, and germs identified. If there were infections at more than one site in the same patient, these were counted as separate infections. All information collected by the nursing staff was presented, discussed, and evaluated by an infection control specialist (infectious diseases and epidemiology), and cases of contamination and colonization were ruled out. The actions to be followed were then defined, such as isolation, change or removal of the invasive device, healing, surgical debridement, etc. In deciding on a specific antimicrobial treatment, empirical initiation was assessed by the standards of hospital sensitivity, and based on reports from the microbiology laboratory, the antibiotic susceptibilities of each pathogen were analyzed to adjust the treatment plan.

Samples were processed in the HRAECS microbiology laboratory. The specimens were collected from patients at the request of epidemiological surveillance personnel or treating physicians; the usual methods for sampling (specific, new and sterile vials) were used for this. The specimens were then cultured according to type in selective and differential media. Pathogens were isolated from specimens using standardized methods specified by the Clinical Laboratory Standards Institute (CLSI).^14,15
The antimicrobial susceptibility of microorganisms was determined by using combo panels (Sensititre Diagnostic Systems, Cleveland, Ohio, United States) for Gram positive and negative bacteria. The API 20 C AUX (Biomerieux, S.A., La Balme-les-Grottes, France) and YeastOne panels from Sensititre (Trek Diagnostic Systems, Cleveland, Ohio, USA), were used for the identification and sensitivity of yeast, respectively. Sensitivity tests used met the criteria specified by the CLSI.
Information capture and statistical analyses were performed using the statistical package Stata 12.1 (StataCorp LP, StataCorp 4905 Lakeway Drive, College Station, Texas 77845, United States). Comparisons were made with Pearson’s chi-squared and Fisher’s test. Changes in trends were analyzed by logistic regression and linear regression. A p-value equal to or less than 0.05 was indicative of statistically significant differences.

This study adhered to the Reglamento de la Ley General de Salud en Materia de Investigación para la Salud.¹⁶ It was performed on specimens from legal adults for the purposes of clinical care, with the informed consent of the patient or guardian. The procedures adhered to ethical standards and the Declaration of Helsinki and its amendments.¹⁷

Results

During the study period, 1300 germs were obtained from cultures of patients with nosocomial infections. Samples that reported no growth or repeated samples of the same site taken from the same patient and the same nosocomial infection event were not included. Data from microorganisms isolated from the same patient but with different nosocomial infections (one patient with two or more) are however presented in some cases.

Of the microorganisms isolated, 62.3% (809) were Gram negative bacteria, 22.8% (297) Gram positive, and 14.9% (194) were yeasts. The infections identified were at the surgical wound site (22.3%), pneumonia associated with mechanical ventilation (21.8%), urinary tract infection associated with the Foley catheter (19.3%), venous catheter insertion site infections (18.4%), bacteremia (7.2%), and skin infections (6.1%). These six types of infection represent 95.1% of the events during the period.

Table I shows the complete account of these infections and the changing pattern of events over the four years of follow-up; a decrease is observed in the number and proportion of pneumonias during the period, going from 26.6% (n = 126) in 2010 to 13% (n = 36) in 2012 (p < 0.000); conversely, catheter insertion site infections increased from 11.8% (n = 56) in 2010 to 32.6% (n = 90) in 2012 (p < 0.000); significant changes were also observed in skin infections (which decreased from 7.4 to 1.1%), neuroinfections (which also decreased from 2.5 to 0%), and peritonitis (which increased from 0.0 to 2.5%).

Table II shows the 16 most frequently isolated germs from 2009 to 2012; these 16 species represent 88.1% of the total number of isolates; the change in frequency of these pathogens observed during the years can also be seen; while Pseudomonas aeruginosa is the predominant germ by total number, during the last two years on record (2011 and 2012) Escherichia coli occurred more frequently and significantly increased from 11.8% in 2009 to 16.7% in 2012. It is also noted that Acinetobacter baumannii increased from 2.7 to 8.7% of the total germs isolated per year, while Candida albicans significantly decreased its proportion from 7.5 to 2.9% during the period.

Gram negative bacteria, with the exception of Klebsiella pneumoniae, showed a general upward trend in their antimicrobial resistance patterns during the period. Pseudomonas aeruginosa went from 47.1 to 60.5% imipenem-resistance from 2010 to 2012, although no statistical significance was observed (Table III), while Escherichia coli showed a significant increase in resistance to aztreonam, cefepime, and ceftazidime (p < 0.01, 0.00, and 0.00, respectively) (Table IV). Quite interestingly, Klebsiella pneumoniae showed a significant decrease in resistance to amikacin and piperacillin/tazobactam (p < 0.03 and 0.00, respectively), besides decreased resistance to levofloxacin, imipenem, and meropenem (p < 0.16, 0.08, 0.08, respectively) and increased resistance to cefepime (p < 0.19) (Table V). Table VI shows that Acinetobacter baumannii showed a significant increase in resistance to amikacin (p < 0.04) and increased resistance cefepime, ceftazidime, and ciprofloxacin (p < 0.06, 0.07 and 0.07, respectively).

Gram positive bacteria showed great sensitivity to daptomycin, as resistance was only found in Staphylococcus aureus in 2011 (15.9%), while S. epidermidis and Enterococcus faecalis showed no resistance in the two years with data for this drug (2011 and 2012). Vancomycin remained effective against Gram positive germs, although resistance was found in S. epidermidis, E. faecalis, and S. aureus with stable trends without statistically significant changes. Resistance patterns were stable for S. epidermidis and E. faecalis in penicillins, cephalosporins, fluoroquinolones, and macrolides, whereas for S. aureus downward trends were observed in resistance against ceftriaxone, ciprofloxacin, levofloxacin, moxifloxacin, trimethoprim/sulfamethoxazole, erythromycin, and clindamycin (Table VII).

Discussion

In our study the predominant nosocomial infections (95.4%) were of the surgical wound site, pneumonia, urinary tract, the catheter insertion site, bacteremia, and skin infections. There were variations tending towards decrease in pneumonia and skin infections (p < 0.000 and 0.001, respectively). These coincided with beginning the use of closed systems for secretion suction and chlorhexidine as an antiseptic for wound healing and surgical washing, and the proportional increase in the case of the catheter insertion site (p < 0.000). It is noteworthy that of the 16 most frequently isolated germs (representing 88% of isolates), eight are Gram negative, five Gram positive, and three yeasts. No significant changes were observed in the proportional frequency of Gram negative bacteria except E. coli, which showed an increasing trend (p = 0.017). Yeasts showed significant changes; significant decrease was observed in the frequency of C. albicans, and an increase in C. tropicalis (p < 0.000 and 0.003, respectively). In the case of Gram positive bacteria, S. haemolyticus increased from 1.1 to 5.1% during the study period (p < 0.011), S. epidermidis showed a slight upward trend, although not significant, while E. faecalis and S. aureus showed no change. Pseudomonas aeruginosa remained the most common germ in total (13.8%), although in the last two years of observation E. coli was the most frequent (13.2 and 16.7%, respectively) and the second in overall number; C. albicans was found in third place. Cornejo-Juárez et al.¹⁸ have reported similar findings for nosocomial urinary tract infections at the Instituto Nacional de Cancerología, the oncology center of reference for Mexico City. Weng Xia et al.¹⁹ showed similar patterns in nosocomial pathogens isolated from lower respiratory tract infections in China.

It was generally observed that the presence of Gram negative bacteria and opportunists (Candida spp.) is related to patients with a long hospital stay, high use of antimicrobials, and conditions that cause a state of immunosuppression or severe or critical disease states, which it has been noted in other studies.²⁰

The resistance rates of Gram negative bacteria showed a general upward trend, especially to cephalosporins, although it was also observed for carbapenems, penicillins, aminoglycosides, and fluoroquinolones. Pseudomonas aeruginosa, E. coli, K. pneumoniae, and A. baumannii showed high rates of cephalosporin resistance, which is probably due to the indiscriminate and inappropriate use (in most cases for several days) of ceftriaxone and other third-generation cephalosporins, as antimicrobial "prophylaxis" for clean surgeries in our hospital and in the region. Notably, the resistance patterns of K. pneumoniae show a downward trend for aminoglycosides, piperacillin/tazobactam and carbapenems, and increase only for cefepime, while its proportional rate remained stable during the period.

We believe it is necessary to deepen the analysis of this trend and correlate it with the type of infection, baseline diagnosis, and the medical specialties responsible for the patient during their stay. There has been an overall increase in the presentation of multidrug-resistant P. aeruginosa and A. baumannii, which justifies the continuation of studies tracking resistance patterns and strengthening control programs and antibiotic administration in our hospital.

Although high resistance rates are observed for Gram positive bacteria to penicillins and cephalosporins, the abusive use of these antimicrobials empirically and prophylactically may have generated a trend toward decreased resistance to trimethoprim/sulfamethoxazole, fluoroquinolones, macrolides, and clindamycin in S. aureus strains in our hospital. Despite relatively high rates of vancomycin resistance in S. aureus and E. faecalis (between 12.0 and 25.0% and between 3.6 and 12.5%, respectively), the effectiveness of vancomycin is generally maintained for these germs, and linezolid and daptomycin are still available, for which little or no resistance has been observed, possibly because these drugs are not routinely used, only being prescribed by specialists in infectious disease, internal medicine, and critical care medicine when they are fully justified by microbiological findings or according to clinical practice guidelines.  

With bacterial resistance and multidrug resistance increasing in developing countries, especially in Gram negative bacteria,²¹ and the situation worsening due to the reduced development and production of new antimicrobial drugs,^9,10,11 it becomes increasingly important to have plans and programs for the rational and evidence-based use of these medications, especially third and fourth generation cephalosporins, moxifloxacin, carbapenems, and new drugs targeting Gram-positive bacteria (linezolid and daptomycin).²² 

The infections, pathogens, and resistance profiles identified in this study are useful for physicians’ decision-making in our hospital and in the region;²³ it was shown that Gram negative bacteria are the predominant causative pathogens in nosocomial infections in our environment, as well as showing their high rate of resistance and trends. The treatment of these events is found to be ever more complicated, and they increase hospital stay and cost of care, as well as patient morbidity and mortality.²⁴ It is essential to disseminate and adhere to clinical practice guidelines, standards, and the implementation of innovative programs to monitor and control hospital infections more efficiently, and to establish better isolation techniques, general care, and antimicrobial use.²⁵

Acknowledgments

The authors thank the nurses at the Departamento de Epidemiología Gabriela Martínez Falcón and Yuri Mariela Pérez Hernández for their invaluable work in the surveillance, detection, and control of infectious events. They also thank the Departamento de Microbiología for their continued support in monitoring the isolation and identification of germs, and the Dirección General Adjunta del Hospital Regional de Alta Especialidad Ciudad Salud for their support and endorsement of the hospital’s Servicio de Epidemiología. 

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