ANTIMICROBIAL SUSCEPTIBILITY PATTERNS OF BACTERIAL ISOLATES FROM PATIENTS WITH URINARY CATHETER AT FEDERAL MEDICAL CENTER, UMUAHIA

ABSTRACT

The antimicrobial susceptibility pattern of bacterial isolates from patients with urinary catheter at Federal Medical Center, Umuahia, Abia state, of Nigeria was studied. A total of 33 catheter urine samples were collected from patients admitted at Federal Medical Center, Umuahia. Samples collected were cultured on MacConkey agar and Cystein Lactose Electrolyte Deficient (CLED) agar using the streaking method. Pure colonies of isolate were biochemically characterized, identified and the antibiotic susceptibility test performed using Muller Hinton agar. Out of the 33 samples analyzed, 21 (63.64%) produced significant growth with 23 microbial isolates. The bacterial isolates included E. coil 8 (34.70%), followed by Pseudomnas aeruginosa 5 (21.74%), Klebsiella sp 4(17.39%), Staphylococcus aureus 3 (13.04%) and Proteus mirabilis 3 (13.04%). The isolates showed high resistance to commonly used antibiotics such as ampicillin (100%), tetracycline (95.65%), augumentin (91.30%), cotrimaxole (91.30%), gentamycin (82.61%) and nalixidic acid (82.61%). Intermediate level of resistance was found against ofloxacin (69.57%) and perfloxacin (60.87%). Only nitrofurantoin and ciprofloxacin (56.52% and 43.48% sensitivity respectively) appeared most effective. Therefore, treatment of patients with catheter associated urinary tract infection in this institution should be guided by the result of susceptibility test of isolates and based on doctor’s prescription so as to reduce the incidence of multiple-resistance.

TABLE OF CONTENTS

Title Page                                                                                                                                i

Certification                                                                                                                            ii                                                                                                            

Dedication                                                                                                                              iii

Acknowledgements                                                                                                                iv

Table of Contents                                                                                                                   v

List of Tables                                                                                                                          vi

Abstract                                                                                                                                  vii

CHAPTER ONE

1.0              Introduction and literature Review                                                                            1

1.1       Introduction                                                                                                                1   

 1.2      Aims and Objectives                                                                                                   2

1.3       Literature Review                                                                                                       3

1.3.1    Description of Catheter and Types of Urinary Tract Infection                                  3

1.3.2    Etiologic Agents of Urinary Tract Infection                                                              5

1.3.3    Epidemiology and Risk Factors                                                                                  6

1.3.4    Pathogenesis of Infection                                                                                           7

1.3.5    Virulence Factors                                                                                                        8

1.3.6    Clinical Features                                                                                                         9

CHAPTER TWO                                       

2.0 Materials and Methods                                                                                                     11

2.1.      Study Area and Population                                                                                        11

2.2       Specimen Collection                                                                                                   11

2.3       Preparation of Culture Media                                                                                                 11       

2.4       Microscopy, Culture and Identification of Isolates                                                    11

2.4.1    Gram Staining                                                                                                             12

2.4.2    Biochemical Analysis                                                                                                  12-16

2.5       Antibiotic Sensitivity Test                                                                                          16

CHAPTER THREE

3.0       Results                                                                                                                        18-25

CHAPTER FOUR

4.1       Discussion                                                                                                                   26-27

4.2       Conclusion                                                                                                                  28

References

Appendix

LIST OF TABLES

CHAPTER ONE

1.0       INTRODUCTION AND LITERATURE REVIEW

1.1       INTRODUCTION

The urinary tract is the most common site of nosocomial infection accounting for more than 40% of the total number reported by acute care hospitals and affecting approximately 600,000 patients per year (CDC, 2009; Meers 1988; Warren 1997). Sixty six percent to 86% of these infections usually follow instrumentation of urinary tract, mainly catheterization (Nicolle 2001).The risk of acquiring a urinary tract infection (UTI) depends on method and duration of catheterization, the quality of catheter care and host susceptibility (Kunin and Calvin, 2001).

            Reported infection rates vary widely, ranging from 1% to 5% after a single brief catheterization to virtually 100% for patients with indwelling urethral catheters draining into an open system for more than 4 days (Saint, 2000). Over 20% of patients catheterized and maintained on closed drainage on busy hospital wards may be expected to become infected (Kunin and Calvin 2001). Host factors which appear to increase the risk of acquiring catheter associated UTI include advanced age, debilitating and the post partum state (Mino et al., 1997)

            Catheter – associated UTI are caused by a variety of pathogens including Escherichia coli, Klebsiella species, Proteus species, Pseudomonas aeruginosa, Enterococcus species, Staphylococcus species and Serratia. Many of these microorganisms are part of the patient’s endogenous bowel flora but they can also be acquired by cross – contamination from other patients or hospital personnel or by exposure to contaminated solution or non – sterile equipments (Kunin and Calvin, 2001).

            Catheter–Associated Urinary Tract Infection (CAUTI) in healthy patients is often asymptomatic and is likely to resolve spontaneously with the removal of the catheter. Occasionally, infection persists and leads to such complications as prostatitis, epididymitis, cystitis, pyelonephiritis and gram–negative bacteraemia particularly in high risk patients (Kunin and Calvin 2001).

The last complication is serious since it is associated with a significant mortality, but fortunately occurs in less than 1% of catherization patients (Kregar et al., 1980).

            Although community acquired UTI has been well investigated in different groups of patients in Nigeria ( Odutaola et al; 1998; Ekweozor and Onyemenem 1996), only few studies(Oni et al; 2003; Taiwo and Aderounmu, 2006) have investigated and documented the etiological agents of catheter- associated UTI of or their susceptibility pattern to antimicrobial agents. In places where little have been done , the problem of under reporting same result about the catheter associated  related infection  may bring about excessive and indiscriminate consumption of broad spectrum and higher antimicrobial compound, contributing to the problem of bacterial resistance occurring in the association with catheterization and susceptibility pattern.

1.2 AIMS AND OBJECTIVES 

1.      To isolate the common bacterial pathogens in patients with urinary catheter,

2.       To identify the bacterial pathogens, and,

3.      To determine their antimicrobial susceptibility pattern as this will provide information on the best choice of antibiotic to be useful for treatment of urinary catheter infection in the study area.

1.3       LITERATURE REVIEW

A broad review of literature about urinary catheter in relation to urinary tract infection has been carried out to identify major areas of research and gaps in knowledge.  Some of them are discussed below.

1.3.1    DESCRIPTION OF CATHETER AND TYPES OF URINARY TRACT INFECTION

Catheter is a tube that can be inserted into a body cavity, duct or vessel thereby allowing drainage, injection of fluids, or accesses surgical instruments (Tebbs and Elliott, 1994). The process of inserting a catheter is called catheterization. In most uses, a catheter is a thin, flexible tube (“soft” catheter), though in some uses, it is larger and solid (“hard”). A catheter left inside the body, either temporarily or permanently may be referred to as an indwelling catheter and may remain in a patient for many days or weeks. Where the catheter is temporarily inserted into the bladder and removed once the bladder is emptied, it is known as an intermittent catheter.  Catheters are extensively used in urology and are made of variety of materials, shapes and sizes. Two main group of catheter used in urology are urethral catheter and supra public catheter. Urethral catheter is a drainage tube inserted into the bladder by passing it through the urethra, the natural tube that leads from the bladder to the outside, while the suprapublic catheter is a urinary catheter inserted into the bladder through the abdominal wall (Wadhaw, 2002). Optimal use of catheter with minimal chances of infection, allergy, or irritation requires that catheters have certain characteristics that play an important role in their use, application and acceptance by some patients (Tebbs and Elliott, 1994). Some of the key characteristics of catheter are listed below:

1.      Flexibility: catheters should have the ability to maneuver and travel through curved blood vessels or cavities.

2.      Durability: ability to exist for a long duration while sustaining pressure and liquid flow.

3.      Chemical Compatibility: compatibility to prevent adverse reactions against body tissues, medications and fluids.

4.      Biocompatibility: ability to be accepted by the body without infection or allergic reactions.

5.      Thromboresistance Designed: should be designed to prevent clotting of blood.

6.      Radiopaque: a catheter should have the ability to be tracked during fluoroscopic visualization.

7.      Kink-Resistant Designed: should be designed to prevent clogging and repture and ensure smooth travel through the vessels or cavity

8.      Non-Carcinogenic: low tendency to cause neoplasia (cancer)

9.      Should be able to resist microbial adhesion and biofilm deposition

10.   Should be able to accept surface coating (e.g. hydrogel, antithrombotic, antibacterial) (Colas and Curtis, 2004; Brown, 1995, Tebbs and Elliot, 1994).

Primary and recurrent urinary tract infections are classified depending whether they are first infection or repeated event, complicated and uncomplicated depending on the factors that trigger infections.  Complicated infections as often in men than women, and occur as a result of some anatomical or structural abnormalities such as bladder and kidney dysfunction. Uncomplicated infections are associated with bacterial infection and affect mostly women than men. Urinary tract infection can involve mucosal tissue (cystitis) or soft tissue (pyelonephritis, prostatitis). Anatomically, the infection can be limited to the lower urinary tract (urethritis, cystitis and prostatitis) and the upper urinary tract (pyelonephritis)   (Evans et al., 1982).

1.3.3    ETIOLOGIC AGENTS OF UTI

Urinary tract infections (UTI) are a bacterial infection of the urinary system which consists of the kidney, ureter, bladder and urethra. Many different organisms can infect the urinary tract but by far the most common agents are the gram-negetive bacilli (Braunwald et al., 2001; Wilson and Gaido, 2004). E.coli is the primary cause of uncomplicated infections of the urinary tract including cystitis (Gunther et al., 2001; Sahm et al; 2001). According to an international survey of the antimicrobial susceptibility   of pathogens from uncomplicated UTIs, E.coli accounts for 77.0% of isolates (Kahlmeter, 2003). However, there is some evidence that the percentage of UTIs caused by E.coli is decreasing being replaced by other members of the Enterobacteriaceae (Haryniewicz et al, 2001; Weber et a.l, 1997).

On the other hand, another literature by Braunwald et al.,(2001) indicated that other gram negative rods, especially Proteus and Klebsiella and occasionally Enterobacter, account for a smaller proportion of uncomplicated infections. These organisms plus Serratia and Pseudomonas, assume increasing importance in recurrent infections, associated with urologic manipulation, calculi, or obstruction.

Gram positive cocci were isolated more frequently from a hospital setting and the most common were Enterococcus species (Wilson and Gaido, 2004; Haryniwicz et al., 2001). Staphylococcus saprophyticus – norobiocin –resistant, coagulase – negative species accounts for 10 to 15% of acute symptomatic UTIs in young females. More commonly, Enterococci and Staphylococcus aureus cause infections in patients with renal stones or previous instrumentation or surgery. Isolation of S. aureus from the urine should arouse suspicion of bacteremic infection of the kidney (Braunwald et al., 2001).

E.coli, K.pneumoniae, C. freundii, Proteus, Pseudomonas, Serratia, Coagulase-negative Staphylococcus, Candida albicans are species implicated in catheter- associated urinary tract infection (Braunwald et al., 2001; Oni  et al, 2003; Taiwo and Aderounmu, 2006).

1.3.4    EPIDEMIOLOGY AND RISK FACTORS

Urinary tract infection occurs in every age and in both genders. Women have a higher risk of developing a urinary tract infection than men (Colgan and William, 2011). In women, the tube through which urine travels (urethra) is very short and empties very close to the vaginal opening. Therefore, it is easier for bacteria from the vagina to travel to the urethra and then to the bladder, causing acute cystitis. By contrast, men have a longer urethra which makes it harder for bacteria to travel and settle in the bladder. Antibacterial prostatic secretion also lessens the likelihood of men developing urinary tract infections. Additionally, there is only a narrow band of flesh (the perineum) between the anus and vagina in woman; therefore it is easy for bacteria to move from the anus to the vagina and from there to the urethra and the bladder (Salvatore et al., 2011). A man’s risk for urinary tract infection increases with age. Older men are more likely to experience prostate related problem that could lead to UTI. Children are also prone to UTI .However, estimate of frequency among children vary widely. In a group of children with a fever, ranging in age between birth and two years, two to 20% were diagnosed of a UTI  (Bhat  et al ., 2011).

The epidemiology of UTI is influenced by the pathophysiology of the infections as well as the virulence of the isolates and the immune status of the host. The predisposing factors frequently associated with UTI include: diabetes, uncircumcision, pregnancy, indwelling or intermittent bladder catheterization, urinary tract instrumentation, sexual activity. The non specific factors that can significantly enhance either directly or indirectly the virulence of bacteria are the birth control pill, alcohols, smoking and antibiotics. Hospitalized patients develop UTI more frequently than out patients (CDC 2009; Meers 1988; Warren 1997).

1.3.5    PATHOGENESIS OF INFECTION

In the vast majority of UTIs bacteria gain access to the bladder through the urethra. Ascent of bacteria from the bladder may follow and is probably the pathway for most renal parenchymal infections. The female urethra appears to be particularly prone to colonization with colonic gram negative bacilli because of its proximity to the anus, its short length (about 4cm) and its termination beneath the labia. Sexual intercourse causes the introduction of bacteria into the bladder and is temporally associated with the onset of cystitis; it thus appears to be important in the pathogenesis of UTIs in younger women. In addition, use of spermicidal coated condoms dramatically alters the normal bacterial flora and has been associated with marked increases in vaginal colonization with E.coli

Infection of the renal parenchyma by many species of gram positive (particularly in patients with Staphylococcal bacteremia) clearly occurs by the hematogenous route. Increased pressure on the bladder can cause lymphatic flow to be directed to the kidney. However, evidence for a significant role for renal lymphatic in the pathogenesis of pyelonephritis is unimpressive. The invasion of bacteria to the bladder through the urethra is of paramount importance in the pathogenis of UTI, while the hematogenous route offers a less frequent but significant pathway (Connie et al., 1995).

1.3.6    VIRULENCE FACTORS

All uropathogens are equipped with a variety of virulence factors. The best characterized are those from E. coli (Oelschaeger et al., 2002). However, not all strains of E. coli are equally capable of infecting the intact urinary tract. Bacterial virulence factors markedly influence the likelihood that a given strain, once introduced into the bladder will cause UTI. Among the first vurulence factors that come into play during establishment of a urinary tract infection are adhesins (Oelchlaegar et al., 2002). E. coli which infects and causes diseases of the urinary tracts expresses several adherence factors including type 1 and P fimbriae (Connel et al., 2002) .Type 1 fimbriea are hair like projections that extends  from the surface of E. coli and other genera of the enterobacteriaceae  (Gunther et al ., 2001). These fimbriae bind mannose – containing oligosaccharides via the Fim H adhesive tip protein and are required for colonization of the urinary tract by uropathogenic  E.coli. Besides their primary function as adhesion molecules, several other additional functions can now be attributed to these organelles. They may also function as invasins, promote biofilm formation and transmit signals to epithelial cells resulting in inflammation (Oelsachaeger et al., 2002).

In addition, uropathogenic E.coli strains usually produce hemolysin and aerobactin (a siderophore for scavenging iron) and are resistant to the bactericidal action of human serum. Nearly all E.coli strains causing acute pyelonephritis and most of those causing acute cystitis are uropathogenic. In contrast, infections in patients with structural or functional abnormalities of the urinary tract are generally caused by bacterial strain that lack those uropathogenic properties; the implication is that these properties are not needed for infection of the damaged  urinary tract (Braunwald et al, 2001).

1.3.7    CLINICAL FEATURES

Urinary tract infections have traditionally been viewed as acute and often self limiting infections. However, this concept has been challenged by recent findings demonstrating that an acute bladder infection results from a complex series of host pathogen interactions that can lead to bacterial invasion and persistence and that ultimately can determine the cause of the infectious disease (Schilling et al., 2001). In general, UTIs can be classified as asymptomatic bacteriuria, cystitis, or acute pyelonephritis. Cystitis predominantly involves colonization of the bladder (Gunther et al., 2001).

Patients with cystitis usually report dysuria, frequency, supra pubic pain. The urine often becomes cloudy and malodorous, and it is bloody in about 30% of cases. White blood cells and bacteria can be detected by examination of unspun urine in most cases. However, some women with cystitis have only 10² to 10⁴ bacteria per milliliter of urine, and in these instances bacteria cannot be seen in a Gram stained preparation. Physical examination generally reveals only tenderness of the suprapublic area (Braunwald et al., 2001).

The more severe upper urinary tract disease acute pyelonephritis involves colonization of the kidneys and represents an infection capable of progressing to bacteremia (Gunther et al., 2001). Symptoms of acute pyelonephritis generally develop rapidly over a few hours or a day and include fever, chills, nausea, vomiting, and diarrhea. Symptoms of cystitis may or may not be present. Besides fever, tachycardia and generalized muscle tenderness, physical examination reveals marked tenderness on deep pressure in one or both costovertebral angles. Most patients have significant leukocytosis and bacteria detectable in Gram-stained unspun urine. Hematuria may be demonstrated during the acute phase of the disease; if it persists after acute manifestation of infection have subsided, a stone, a tumor, or tuberculosis should be considered (Braunwald et al., 2001).

Most catheter associated bacteriurias are asymptomatic (Warren 1997). Two studies of hospitalized patients with catheter related UTI found that the majority were asymptomatic, and that patients with and without UTI did not differ in signs and symptoms of fever, dysuria, urgency, and flank pain. Importantly, patient’s report of UTI symptoms, fever, and elevated plasma white blood cell count did not predict catheter-associated UTI (CAUTI).

Urinary white blood cell count was the best predictor of CAUTI (Medigan and Neff, 2013). The complications in short-term catherized patients include fever, acute pyelonephritis, bacteremia and death; patient with long term catheters in place are at risk for these complications and catheter obstruction, urinary tract stones, local periurinary infections, chronic renal inflammations, chronic pyelonephritis, and over years bladder cancer (Warren, 1997).    

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