Urinary tract infection--a dangerous and unrecognised forerunner of systemic sepsis.VN Acharya
Dept of Nephrology, Seth G. S. Medical College & KEM Hospital, Parel, Bombay, India., India
Keywords: Antibiotics, therapeutic use,Drug Resistance, Microbial, Human, Incidence, India, epidemiology,Microbial Sensitivity Tests, Recurrence, Risk Factors, Severity of Illness Index, Urinary Tract Infections, drug therapy,epidemiology,microbiology,
Urinary tract infection is an important cause of morbidity and mortality in Indian subjects, affecting all age groups across the life span. Though Escherichia More Details Coli, which is normally present in the gastrointestinal tract, is the commonest causative organism, other gram negative colonic bacteria have been gaining prominence in India over the last two decades,. Because of the proximity of the gut to the urinary tract, these organisms ascend through the urinary passage to the urinary bladder and the kidneys to produce infection.
Kass (1956) first introduced the concept of significant bacteriuria in an attempt to negate the problem of growing contaminants. He demonstrated that the presence of more than 10 colony, forming units of bacteria per mi of urine in a single specimen indicated bacteriuria with a probability of greater than 80% which could be increased to more than 90% or upto 99% when 2 or 3 consecutive specimens were examined. Though Kass' definition of significant bacteriuria retains its general usefulness, there are clinical situations where counts between 10 - 10 may be significant. In symptomatic patients, increased fluid intakes may dilute the urine and decrease bacterial counts or they may have received antibacterial therapy in the recent past. In some patients with recurrent infection and uroepithelial damage, the bacterial count may not reflect clinical realities. To prove the significance of a lesser colony count in such situations, the urine must be obtained by suprapubic bladder aspiration, wherein any bacterial growth is confirmatory of the diagnosis of urinary tract infection (UTI).
We have been dismayed by the steady change over the years in the urinary bacterial flora. By a simple Dip Slide technique used for semiquantitation of significant bacteriuria, it was noticed that the incidence of UTI was 36,3 % in hospitalised patients and 16.5% in a non-hospitalised outpatient population group. A continuous observation done over a 15 year period as a part of a longitudinal study has revealed that Klebsiella has replaced E.Coli as the predominant urinary pathogen. This change has been noticed more prominently after the free usage of orally administered semi-synthetic penicillins began in India in 1975. In the 1980's, a significant rise in other Gram negative nonfermenting bacteria (Enterobacter, Providence group, Citrobacter, Alkaligenes Faecalis etc.) producing UTI has occurred, coinciding with free-usage of the cephalosporins. The most disturbing findings of this longitudinal study has been a gradual and definite increase of microbial resistance to many routinely used antibacterial agents like ampicillin, amoxicillin, tetracycline and cotrimoxazole to which less than 25% of isolates are sensitive. The superpower antibiotics like sisomicin, netilmicin, cefotaxime introduced into the Indian market after 1985, too, have been affected by this problem of resistance. The third generation cephalosporins (ceftazidime) and aminoglycosides (amikacin) are the only antibacterials with low resistance (5.2 to 18%) noted upto 1986. This en masse resistance seems to be largely plasmid mediated by ? lactamase producing bacteria.
Urinary tract infection is an excellent example of host-microbe interaction. Microbial factors have shown a rather distressing trend. Besides the changing pattern of urinary pathogens and the increasing antimicrobial resistance manifested by them, there are other microbial factors too. Amongst the common E Colicausing UTI, there are certain restricted O - serotypes viz 01, 02, 04, 06, 07, 09, 015 which are the main uropathogens as seen in studies from our own country. That these confer virulence to the pathogens, has been supported by the frequency with which the symptomatic UTI follows reinfection with a new serotype of E Coli after overt bacteriuria has been eliminated by treatment.
The ascent of E Coli from the periurethral flora into the urinary tract is related to bacterial adherence to the epithelial cells of the urinary mucosa as demonstrated by Eden and his colleagues from Sweden. They demonstrated the presence of mannose resistant fimbriae on the bacterial surface, which attach to specific receptor sites (genetically coded) on uroepithelial cells. Over the years overwhelming evidence has accumulated to show that bacteria with mannose resistant fimbriae - (P-fimbriae) are specifically associated with UTI.
Amongst the host susceptibility factors which play a pivotal role in host-microbe interaction are secretory status of the uroepithelial mucosa, residual urine, outflow obstruction, vesicoureteric reflux (VUR), calculi, congenital and acquired structural-abnormalities of the urinary tract, pregnancy, diabetes mellitus and instrumentation. Moreover, uncomplicated UTI may have a rather benign course, whereas complicated UTI has been associated with increased morbidity and mortality.
Clinically, it is very relevant to differentiate between infection restricted to the lower urinary tract and infection of the upper urinary tract. Diagnosis of the site of infection based on symptoms and signs can be quite inaccurate and hence other methods of diagnosis might have to be resorted to. Green and Thomas demonstrated that the serum levels of antibody directed against lipopolysaccharide antigen present on the bacteria, particularly that of E Coli, are commonly raised with upper urinary tract infection. This is useful when increasing antibody titres are demonstrated on the serial studies. Failure of elevated antibody titres to return to normal levels over a period of follow-up may indicate chronicity and the possible development of chronic interstitial nephritis (chronic pyelonephritis).
The problem of asymptomatic bacteriuria and its treatment has been debated all along. In pregnant women, it has been conclusively shown that treatment minimises the risk of maternal and fetal complications,. However, there is no substantial evidence to suggest that treatment is required for uncomplicated asymptomatic bacteriuria in non-pregnant women. Asymptomatic bacteriuria in association with obstruction, stone and other conditions predisposing the papillary necrosis like diabetes mellitus, sickle cell disease and analgesic abuse, do need treatment. Immunosuppressed patients with asymptomatic bacteriuria run an increased risk of bacteremia if renal infection develops and hence need to be treated.
Considering the factors of convenience, cost, compliance and reduced side-effects, lower urinary tract infection encountered for the first time, could be treated with a single dose therapy. Amoxicillin 3 gm, doxycyclin 300 mg and cotrimoxazole (trimethoprim 320 mg and sulphamethoxazole 1600 mg) have been used with cure rates of more than 85%,. The suggestion that single dose therapy was not only successful, but distinguished lower from upper tract infection has been questioned. It is difficult to distinguish rapid reinfection from a true relapse due to persistence of periurethral colonization.
In a number of women, recurrence of infection occurs only after sexual intercourse. A single, low dose, postcoital, antibacterial prophylaxis such as 100 mg of nitrofurantoin or 1 gm of nalidixic acid could prevent infection in many of them.
Acute and chronic bacterial prostatitis has been increasingly seen in young men of today. These need special scrutiny and use of lipid-soluble antibacterials, which will penetrate the prostate such as cotrimoxazole, doxycycliry, norfloxacin or injectable gentamicin in the acutely in febrile patients.
Acute upper tract infection needs appropriate therapy with antibacterials to which the organisms have been shown to be sensitive. Severity of illness will determine the extent of therapy. In acutely ill patients with high fever, loin pain, vomiting etc who are hospitalised, gentamicin in combination with amoxicillin or ampicillin may be the treatment of choice pending a urine culture and sensitivity report. Such infections account for 15-20% of all cases of bacteremia in community practice and almost 35% in hospital practice. Metastatic infection of the heart, bone and other sites may also result. In elderly males, this may be related to prostatic infection. In childhood, it is the commonest cause of acute bacterial infection accounting for significant morbidity and mortality. The clinical picture can vary from the shocked septicaemic newborn presenting with seizures and renal failure to the mild to moderate illness in almost any age group of children. The first episode of bacterial infection of the urinary tract very often develops in the first year of life, but goes undetected due to a lack of symptoms referable to the urinary tract, combined with non- consideration of this diagnosis related to a lack of awareness amongst the doctors. In infancy, septicaemia, jaundice, weight loss, feeding problems, taiiure to gain weight and vomiting may be due to urinary tract infection.
Reflux nephropathy is one of the most preventable causes of renal failure, both in children and adults, with effective prevention achievable in childhood. In these conditions, scars appear by the age of 4-5 years. Thereafter, the risk of new or progressive scars with age diminishes remarkably. The VU reflux also tends to improve or dissappear as the child gets older. Hence, these infants and children with VUR are managed with low dose, long-term prophylaxis until the reflux either resolves spontaneously or until the risk of progressive scarring is deemed to be minimal. The only way to reduce the incidence of reflux nephropathy and to prevent renal damage is by early detection and treatment of the first infection in infants. Increased awareness amongst general practitioners and paediatricians of the importance of making an early diagnosis in infants and toddlers with the help of improved investigative facilities could attain this goal. It would also be important to emphasise the value of blood pressure check up in such children to detect and control morbidity due to progressive renal disease.
It must be emphasised that increasing resistance of bacterial pathogens is a true danger to successful
therapy of UTI. Quinolones, which have been empowered with protection against plasmid mediated resistance have also been showing a disturbing trend in the last 5 years (1987-1992). Quinolones like norfloxacin, ofloxacin, pefloxacin and ciprofloxacin have shown better sensitivities against multiple resistant urinary pathogens, but have manifested considerable cross resistance amongst themselves. This poses a real threat to successful therapy of UTI by these so-called wonder drugs developed at an enormous cost.
In our own study, between 1987-1992, blood samples from septicaemic patients have revealed Gram negative pathogens, which have shown sensitivity to quinolones (85%) followed by ceftazidime (75%) and amikaoin (70%) . Use of quinolones as a routine should be discouraged and their use restricted only to grave situations associated with multiple drug resistant strains after their proper antibacterial sensitivity data is available. This alone, would curb the problem of resistant UTI emerging as a dangerous and unrecognised forerunner of systemic sepsis in our country.