Should asymptomatic bacteriuria be treated in diabetic individuals

Asymptomatic bacteriuria (ASB) is defined as the recovery of the same microbe in at least two consecutive urine cultures in quantity of < 105CFU/ml (colony forming units) with a simultaneous absence of clinical symptoms of urinary tract infection. It is seen more frequently in diabetic individuals and especially in diabetic women. In a recent European epidemiological study it was found that 26 percent of diabetic women had ASB versus 6 percent of control subjects.

Factors that have been incriminated in the increased incidence of ASB in diabetic women are hyperglycaemia (and the resultant disturbance of leukocytes' function), poor glycaemic control, more frequent use of urinary bladder catheters (as is observed in diabetics), presence of autonomous nervous system neuropathy and relapsing vaginal infections, as well as the more frequent presence of anatomic abnormalities (also observed in diabetics) such as cystocoele, cystourethrocoele and recto-coele. It appears that the presence of diabetic neuropathy has particular importance. Decreased sensation of the urinary bladder leads to its distention, urinary retention and increased residual urine volume, resulting in an increased sensitivity towards infections as well as the appearance of infections with a smaller initial number of pathogenic micro-organisms.

According to all large studies, there is no difference between the responsible pathogenic microbes in diabetics and non-diabetics.

The importance of ASB lies in the probability of it causing complications and more specifically in the production of upper urinary tract infections and decrease in renal function. It has indeed been observed that upper urinary tract infections are more frequent and more serious in women with Type 2 DM and ASB. This has not, however, been proven for women with Type 1 DM. As regards the effect of ASB on renal function, there are no sufficient data. Only one prospective study (of 18 months' duration) showed that women with Type 1 DM and ASB had a tendency for deterioration of renal function compared to Type 1 diabetic women without ASB; however, the amounts did not reach statistical significance. It should also be noted that the follow-up interval was relatively small. For the resolution of this question, larger and longer-lasting prospective studies are required.

Therefore, returning to the initial question of whether ASB in diabetic women requires treatment or not, it has to be stressed that this question cannot be answered definitively. There are certainly selected cases in which the treatment of ASB is absolutely indicated. Thus, ASB should, without any doubt, be treated in pregnant women with DM, in whom treatment of ASB has been proven to decrease the probability of pyelonephritis as well as the probability of premature birth and low birth-weight infants. The treatment of ASB is also absolutely indicated in individuals who are to undergo urological operations as well as those who have had kidney transplantation.

In the general diabetic population, several experts, mainly Americans, believe that ASB should be treated, aiming at the reduction of upper urinary tract infections, but also - probably - at the protection of the kidneys. European specialists, however, do not on the whole conform to this opinion. The scepticism of many researchers is based on the absence of a large study that proves the benefit of treatment. Recently, a well-planned study in 105 diabetic women with ASB (half of whom received at the beginning of the study antimicrobial treatment for 14 days, while the others received a placebo) showed no difference in the probability of urinary tract infection in the following 27 months between the two groups. In other words, women who received the initial antimicrobial treatment had no benefit at all.

Nevertheless, in order to answer with certainty the question of treatment of ASB in diabetic women, large prospective studies, for longer duration and probably with other treatment strategies are required.

Based on the above evidence, it is not surprising that there is a lack of a generally accepted position concerning the necessity of screening all diabetic women for detection of ASB. The supporters of treatment are in favour of regular screening while the sceptics do not support the regular screening of all diabetic women but only of those at high risk for upper urinary tract infection, such as individuals with neuropathy and/or with urogenital system anatomic abnormalities.

CASE STUDY 1

A 62 year old woman was brought to the hospital because of fever and pain in the left lower extremity. The symptoms had begun two days prior and had shown a constant deterioration. The patient had had known Type 2 DM for 10 years, under treatment with insulin, with poor metabolic control. She also had known diabetic background retinopathy and diabetic neuropathy. Physical examination revealed fever 38.8° C (101.8° F), a pulse rate of 125 beats/min, respiratory rate of 24 breaths/min and arterial pressure of 90/60 mmHg. The entire left lower extremity was oedematous, dark red, hot and sensitive. There were a few haemorrhagic blisters on the anterior surface of the thigh and shin. There was coexistent pain, redness, warmth and sensitivity in the ipsilateral groin, the left lower quadrant and the lower part of the left lateral abdomen. Palpation of the whole left lower extremity, but also the left lateral abdominal wall, revealed crepitus. There was ulceration in the big toe of the left foot with a necrotic eschar. Routine laboratory examinations revealed a haemoglobin level of 13.7 g/dl, white cell count of 13.6 k/mm3 and plasma glucose level of 358 mg/dl (19.9 mmol/L).

What is the diagnosis? How should the patient be managed? What is the responsible micro-organism? Was there a predisposing factor that led her to this condition?

A plain radiograph of the left lower extremity, and subsequently a computed tomographic scan of the same extremity and the abdomen, were performed. Both exams revealed the presence of a large quantity of air in the soft tissues along the fasciae of the affected lower extremity and the left lateral abdomen. A small quantity of air was also observed in the gastrocnemius muscles. Based on the clinical picture and the above mentioned findings, the diagnosis of necrotizing fasciitis and myonecrosis was considered.

This necrotizing infection is an emergency medical condition. It manifests itself with signs of sepsis, has a fulminant course and a mortality rate of 30-60 percent. The most frequent localizations are the upper and lower extremities as well as the abdominal wall. The prognosis depends on prompt diagnosis and treatment. The revelation of air in the soft tissues, which can be demonstrated on a plain radiograph, ultrasound, computed or magnetic tomography, is very important for the diagnosis. Computed tomography has the advantage of offering information on the extent of necroses as well as on the possible coexistence of intraabdominal or pelvic abscesses, and it is usually more easily available and cheaper than the magnetic tomography. Computed tomography findings include asymmetrical thickening of fasciae in combination with the presence of air along them. In advanced cases, air is observed in contiguous muscles, and the diagnosis of myonecrosis is complete.

Based on the above diagnosis, the patient was immediately led to the operating room for debridement of necroses. Simultaneously, parenteral administration of liquids, insulin and antibiotics was begun. Specifically, crystalline penicillin G at a dose of 6 x 106 units every 6 hours, clindamycin 900 mg every 8 hours and piperacillin-tazobactam, 4.5 g every 8 hours were administered. The prognosis was poor due to the large extent of affected tissues.

During surgery, extensive necroses of the soft tissues in the muscular aponeuroses of the whole left lower extremity and the abdominal wall were detected, and these extended to the subcutaneous tissue and partly to the gastrocnemious muscles. There was a copious quantity of malodorous purulent fluid with brown colour. Gram stain showed a polymicrobial colonization with Gram (+) cocci and Gram (—) bacteria. Later on, the cultures of necrotic tissues certified the presence of the following microbes: Staphylococcus epidermidis, Bacteroides ureolyticus, Bacteroides fragilis, Pseudomonas aeruginosa and Enterococcus faecalis.

Necrotic fasciitis is categorized as Type I (infection from at least one anaerobic micro-organism and one or more aerobic) and Type II (caused by group A streptococci, with or without staphylococci). Port of entry of the micro-organism(s) can be some small or large trauma, although often it cannot be found and remains unknown. In the case of this particular patient, the port of entry was very probably the ulcer in the big toe.

In 50 percent of cases of necrotizing fasciitis, DM is the underlying disease (mainly in patients with poor metabolic control). Other predisposing factors for the appearance of this severe infection are alcoholism and morbid obesity.

The cornerstone of treatment is surgical debridement. At the same time antibiotics should be administered. The combination of penicillin with clindamycin and additionally an aminoglycoside or second generation cephalosporin or piperacillin/tazobactam or co-trimoxazole is recommended.

The patient underwent a surgical intervention, during which multiple incisions of the affected soft tissues were performed, with extensive debridement of the necrotic tissues. Afterwards, she was transferred to the intensive care unit, where despite the administration of large doses of antibiotics (as mentioned before), she developed septic shock and died 24 hours later.

Note: It is stressed that necrotizing fasciitis/myonecrosis is more frequent in persons with DM but, in the diabetic population as a whole, it is an infrequent disease. However, the gravity of the illness and the need for immediate medical intervention to save the patient's life necessitated the inclusion of the present case.

In DM, lower extremity gangrene (dry or wet) is much more frequent. Analogous patient cases are reported in Chapter 17.

CASE STUDY 2

A 57 year old woman presented to the hospital because of continuous, blunt pain in the left side of the abdomen, extending to the back, high fevers and vomiting for the previous four days. She also reported mild dysuric symptoms for the last week. She had a history of Type 2 DM for seven years, under treatment with oral antidiabetic medicines. Her glycaemic control was not satisfactory. Physical examination revealed fever (39.2° C [102.6° F]), tachycardia (110 per min), tachypnoea (26 per min) and mild confusion. Arterial blood pressure was normal (130/80 mmHg). Chest and heart examinations were normal. Palpation of the abdomen and percussion of the left flank area revealed tenderness over the left upper quadrant and left lateral abdomen.

The initial haematologic/biochemical tests showed increased white blood cell count (16.6 x 109/L) with 94 percent neutrophils, normal number of platelets (247 x 109/L), ESR 130 mm/hour, plasma glucose 315mg/dl (17.5 mmol/L), urea 85 mg/dl (14.1 mmol/L), creatinine 1.5mg/dl (132.6 imol/L), alkaline phosphatase 623 U/L (normal < 260 U/L), and yGT 83 U/L (normal < 32 U/L). Serum bilirubin levels were within normal limits and transaminase levels slightly elevated (1.5 x above upper limits of normal). Blood pH was 7.33 and HCO— 16 mEq/L. Urinalysis showed 25-30 WBCs per high power field with no ketones. Plasma ketone concentration was normal as well.

A plain abdominal radiograph showed the suspicion of air in the parenchyma of the left kidney, and an abdominal ultrasound revealed a small subcapsular collection of fluid ipsilaterally. A computed tomographic scan of the abdomen showed an increase in the size of the left kidney and intraparenchymal collection of air, and also confirmed the small subcapsular collection of fluid.

A diagnosis of sepsis due to emphysematous pyelonephritis was considered. The patient was hospitalized and hydration and immediate intravenous administration of antibiotics was started. Immediately after blood and urine cultures were taken, she was started on intravenous piperacillin/ tazobactam treatment. A urologist was consulted because of the possible need for nephrectomy. It was initially decided to insert a transutaneous (under ultrasound guidance) drainage catheter in the subcapsular fluid collection, through which a small quantity of haemorrhagic fluid was drained. The patient was placed under very close monitoring with a low threshold for nephrectomy in case her condition deteriorated.

Blood and urine cultures isolated Klebsiella pneumoniae, which was sensitive to the already administered antibiotics.

Hyperglycemia was controlled within the first 24 hours. After 72 hours the patient's fever had subsided and the acidosis had recently been reversed. The transutaneous catheter was removed because fluid drainage had ceased. The patient was afebrile 15 days later. A computed tomography of the abdomen was repeated, which showed disappearance of both the air from the renal parenchyma as well as of the subcapsular fluid collection. The patient was discharged from the hospital and continued treatment with oral antimicrobials for another 15 days with co-trimoxazole, based on the culture's sensitivities.

Emphysematous pyelonephritis is a rare but serious infection of the kidney, characterized by the production of air, either intrarenally or perirenally. More than 90 percent of cases are observed in diabetic patients. The main microbes that cause the disease are those involved in the usual infections of the upper urinary tract. In most cases E. coli is isolated. Less frequently Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Aerobacter aerogenes and Citrobacter are isolated. In 20 percent of cases more than one microbe is isolated. Very occasionally, even fungi can be involved. The typical anaerobic bacteria that produce air are extremely seldomly reported as causes of emphysematous pyelonephritis.

There are no specific symptoms of the disease. Pneumaturia can be present, but this is also observed in fistulas between the intestine and the urinary tract. Only in one third of cases does the plain radiograph detect the presence of air in the parenchyma or perirenally. However, according to other studies, this percentage can be much larger. Ultrasound, although useful for the diagnosis of possible obstructions of the urinary tract, is not sensitive for the localization of air in the kidney. The preferred examination method is the computed tomography of the abdomen, which determines the extent of the disease both intra- as well as perirenally.

There are various classifications of emphysematous pyelonephritis, mainly regarding the localization, extent and form of the presence of air. According to the simplest of these, Type I emphysematous pyelonephritis is characterized by complete absence of fluid collection in the computed tomography as well as by the scattered presence of air. In the Type II form of the disease, collection of fluid intrarenally or perirenally is observed as well as presence of air under the form of small or bigger bubbles in the parenchyma or inside the urinary drainage tract. The latter form has a better prognosis. Other unfavourable prognostic factors are acute renal insufficiency, thrombocytopenia (implying diffuse intravascular coagulation), a disturbed level of conscience and shock.

Together with the proper antimicrobial treatment, the substitution of the usually existing fluid deficit and the correction of hyperglycaemia and electrolyte disturbances are of paramount importance. Traditionally, emergency nephrectomy was the treatment of choice for all cases. Today, this treatment is indicated when the disease is extensive and/or has a fulminant course as well as when there is no response to the initial conservative treatment. Drainage with placement of a transutaneous catheter (under computed tomography or ultrasound) is often used in cases of localized disease and fluid collection.

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

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