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Jane, a 40-year-old woman, walked into the emergency department at 12 am with a complaint of lower back pain and a burning sensation during urination. She had these symptoms for about 2 days. Her vital signs were normal and the diagnosis was apparent. A clean-catch urine sample was collected and sent to the laboratory with a provisional diagnosis of UTI. The physician prescribed cotrimaxozole 160/800mg PO q12h for 5 days. Jane was requested to return for a second urinalysis in a week's time.
A short review of the aetiology of the disease indicated in the scenario. (200-300)
A urinary tract infection (UTI) is characterized by the presence of bacteria (bacteriuria) and white blood cells (pyuria) in the urine of a patient with symptomatic infections that affect urethra, bladder and kidneys (urethritis, cystitis and pyelonephritis respectively).1 Generally, UTIs can be categorized into complicate and uncomplicated infections.2
Gram negative rod Escherichia coli, (E coli) is the most prevailing cause of UTI, followed by Staphylococcus saprophyticus.1,3,4,6 E coli accounts for 75%-90% of acute community-acquired, uncomplicated UTIs.4 Moreover, microorganisms such as Klebsiella pneumonia, Proteus mirabilis and Enterococcus faecalis are also common uropathogens.1,3,4 As in hospital-acquired or other complicated UTIs, it is noted that other Gram-negative microorganisms include Pseudomonas aeruginosa, Proteus, Enterobacter, Serratia cause more infections than in community-acquired infections while E coli still remains as a common pathogen.4
Besides that, UTIs are affected by predisposing host factors such as age, gender, diabetes, sexual activity, urinary tract obstruction, neurologic dysfunction, previous antimicrobial use, catheterization or immunosuppression that complicate UTI.1,4,6 As a result, complicated UTI has a more diverse etiology than uncomplicated UTI.6 UTI is more prevalent among female compared to male with a ratio of 30:1.1,6 This is due to the fact that shorter female urethra and the close proximity of the urethra to the anus are less effective in deterring bacterial colonization and infection.1,3,4,5 Its incidence also increases with age and with sexual intercourse.1
In brief, an infection can occur when the organisms enter into the urinary tract via either an ascending route from the urethra or a descending route through the kidneys. The organisms originate from the bowel and spread to the perineum, the vaginal and vaginal introitus (in women) via the ascending route. Urethra and bladder are then can easily be infected once the periurethral area and vaginal introitus are colonized by bacteria.2 The ascending of the organisms up the urethra to the bladder is the most common pathway of acquiring a UTI.1,4
Was the doctor's presumptive diagnosis justified? Describe how you reached this conclusion citing microbiological, symptomatic evidence and literature to support your argument.
The urinalysis (UA) is an array of laboratory tests carried out in patients suspected of suffering from UTI.4 Firstly, 20-30ml urine of the Jane was discarded after cleaning her urethral opening area. The next part of urine flow was collected and should be refrigerated promptly if the specimen cannot be cultured immediately. This is to avoid inaccurate elevated bacterial counts.7
Urine cultures in the bacteriology laboratory were performed on three different agars, namely the MacConkey agar, cystine lactose electrolyte-deficient (CLED) agar and mannitol salt agar (MSA). The related bacteria has formed red circular colonies on MacConkey agar and the acid production has turned the agar to red colour while they grew as yellow colonies on CLED agar and transformed the agar to yellow. On the other hand, they showed no growth in MSA (a selective medium for Gram-positive Staphylococcus aureus). Hence, it can be deduced that the bacteria grew on the agar plate is a strong lactose fermenter (e.g. Escherichia coli).8,9
Microscopic observation was subsequently performed in order to identify the microorganism being cultured. Gram-staining was applied on the colony sample and it appeared as pink colour under the microscope. This indicates that it is a Gram-negative bacterium. The bacterium was in non-aggregated short bacillus shape. Moreover, biochemical test was conducted and it showed that the microorganism is oxidase negative and hence, it does not contain cytochrome oxidase.
E coli are part of the normal flora in the human.8 They reside in human colon and cause frequent opportunistic infections.9,10 Some common infections caused by E coli include UTI, sepsis, neonatal meningitis, and "traveler's diarrhea".10
On the analysis of the signs and symptoms of the clinical scenario, Jane's vital signs were normal but she was suffering from lower back pain and a burning sensation during urination (dysuria). All these symptoms are associated with lower UTIs (e.g. cystitis) but not upper UTIs as patients with upper UTIs may have symptoms such as fever, loin pain, nausea and vomiting.1,3,4
Based on all the observations above, it can be concluded that physician's diagnosis of urinary tract infection is justified, with Escherichia coli being the causative pathogen.
Could the doctor's selection of antimicrobial therapy following the presumptive diagnosis be criticized? Would you have recommended any alteration in the initial therapy or in the subsequent treatment plan following the availability of the microbiological data? Justify your decision and make reference to the literature. (500-700)
Since the disease is diagnosed as bacterial infection, only antibiotics will be considered as the antimicrobial therapy. The following characteristics should be considered during the selection of an ideal antimicrobial for the treatment of UTIs 2:
Bactericidal activity against the most common uropathogens
High, sustained concentrations in both urine and urinary tract tissues
Withdraw uropathogens from the vagina and bowel efficaciously, without significantly changing normal flora in this area
Effective via oral administration with few doses per day
Minimal and mild unwanted reactions
Relatively low cost
Safety for use in children and women
The minimum inhibitory concentration (MIC) test on E coli shows the following results:
Table 1: MIC test on E coli (99words)
Based on table 1, it is showed that E coli have high resistance towards Ceftazidime among all four types of antibiotics due to the highest MIC value. Ceftazidime is third-generation of Cephalosporin with excellent activity against pseudomonas and also active against other Gram-negative bacteria.11 Ceftazidime is bactericidal in action, can be used to treat both complicated and uncomplicated UTIs caused by Pseudomonas aeruginosa, EnterobacterÂ species, ProteusÂ species,Â KlebsiellaÂ species, andÂ E coli.Â However, it is not metabolized in the body and 80-90% of the active form is excreted unchanged into the urine.12,13 Hence, ir must be taken into the body by deep intramuscular(IM) injection or intravenous(IV) injection.11 This results in Ceftazidime is not being selected as the antimicrobial agent since an ideal agent for the treatment of UTIs should possess the characteristic of effective via oral administration.2 (133 words)
Amoxicillin is a derivative of Ampicillin. Both antibiotics are under broad-spectrum penicillins and have a similar antibacterial spectrum. In comparison, amoxicillin has a better oral absorption and thus producing higher tissue and plasma concentrations.11 It works by binding to specific penicillin-binding proteins (PBPs) in the bacterial cell wall and inhibits assembly of the peptidoglycan chains. This in turn leads to lysis of the bacterium and thus cell death.14 Studies have revealed that more than half of Gram-negative rods causing UTIs can produce Î²-lactamses that inactivate Amoxicillin and thus resistant.3 Hence, it is not an appropriate antimicrobial agent in this scenario. The alternative antibiotic that can be used instead of amoxicillin is Augmentin (combination of amoxicillin and clavulanate) with improved activity against Î²-lactamses and thus most Gram-negative rods.3,15 (124 words)
Ciprofloxacin and co-trimoxazole are currently considered as first-line antimicrobials for the treatment of UTIs.2 Ciprofloxacin, the most generally used fluoroquinolone, is also a broad-spectrum antibiotic with excellent activity against Gram-negative bacteria (e.g. Enterobacteriacieae) and moderate activity against Gram-positive bacteria.11,14 It inhibits and interferes with the supercoiling of bacterial DNA topoisomerase type II (tyrase), which are essential for DNA replication, recombination and repair.14 It is normally indicated for pseudomonal UTI.15 Even though it has the lowest MIC among all four types of antibiotic; which proved that it is clinically effective, fluoroquinolone is expensive.2 Apart from that, it may bring about adverse effects such as gastrointestinal tract upsets and hypersensitivity reactions.14 (105 words)
Co-trimoxazole is recommended by Infectious Disease Society of America (IDSA) guidelines on UTI as first-line therapy in patients without allergy and in areas where the incidence of co-trimoxazole resistance among E coli is less than 20%.4,15 It is the combination of trimethoprim and sulfamethazole with a ratio of 1:5 to produce a synergistic activity at two steps in the synthesis of folic acid.2,11 They are bacteriostatic in action when they are used separately but in combination they are bactericidal against most uropathogens.4 Sulfamethazole is a structural analogue of p-aminobenzoic acid (PABA). It competes with PABA for the enzyme dihydropteroate synthetase, thereby preventing the formation of folic acid. Trimethoprim, another bacteriostatic agent, is a folate antagonist that interferes with folic acid metabolism by inhibiting the enzyme dihydrofolate reductase and subsequently the formation of active form of folic acid, tetrahydrofolate.14 Common unwanted effects associated with the usage of co-trimoxazole include nausea, diarrhoea, headache, hyperkalaemia and rash. It is also associated with rare but serious adverse effects such as Stevens-Johnson syndrome.11 (163words)
In this case, the patient is prescribed with oral administration co-trimoxazole 160/800mg. The physician's selection of antimicrobial agent is appropriate as co-trimoxazole is clinically proven to be effective in initial treatment of uncomplicated lower UTI.2,16 Moreover, co-trimoxazole is preferred due to its high cure rate, low expense and only moderate level of side effects.16 However, the treatment duration can be amended to ensure that the UTI can be eradicated effectively in a shorter period. This can be done by changing the 5-day courses of co-trimoxazole to 3-day courses as studies have revealed that the latter appears to have similar clinical efficacy as 7-day regimen. Three-day courses are also coupled with fewer side effects, cost and vaginitis.2 In addition to antimicrobial therapy, the patient should be advised to have sufficient fluids intake to assist the normal urinary flow.3,4 (133words)
If there is no improvement in the patient's condition upon the completion of the course of microbial therapy, this indicates that E coli in the patient are resistance to co-trimoxazole. Ciprofloxacin is then can be used to replace co-trimoxazole with a dosage of 250-500mg tablet twice daily.4,11 (46 words)