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Infections of the urogenital tract


Infections in the intensive care unit (ICU) contribute significantly to patient morbidity. Depending on the type of ICU, nosocomial infections may account for 70% of infections. Nosocomial infections of the urogenital tract are frequent and sometimes underestimated in the ICU.

Definition

Urinary tract infection (UTI) can be the primary cause for admission to the ICU or can be acquired after intensive care procedures. Because patients are frequently sedated in the ICU, clinical diagnosis of UTI is often difficult. Nevertheless, UTI is an important cause of morbidity and antibiotic resistance in the ICU. Complicated UTI is a highly heterogeneous entity, with a common pattern of the following factors , :

  • Anatomic, structural, or functional alterations of the urinary tract, which significantly impede urodynamic properties (e.g., stents, urine transport disturbances, instrumentation of the urinary tract, stones, tumors, or neurologic disorders)

  • Impaired renal function caused by parenchymal diseases or prerenal, intrarenal, or postrenal nephropathies (e.g., acute and chronic renal insufficiencies, cardiac insufficiency)

  • Accompanying diseases impairing the patient’s immune status (e.g., diabetes mellitus, liver insufficiency, use of immunosuppressive agents such as corticosteroids, acquired immunodeficiency syndrome [AIDS], hypothermia)

Etiology

Causative pathogens of UTI are almost exclusively bacteria and yeast. Viral pathogens are only found in patients with severe immunosuppression, such as after bone marrow transplantation. High antibiotic pressure and special circumstances in the ICU modulate the microbial spectrum. Escherichia coli is the most frequent pathogen but occurs less frequently in nosocomial UTI than in uncomplicated community-acquired UTI. Other Enterobacteriaceae may also be uropathogenic (e.g., Klebsiella, Proteus , Enterobacter , Serratia , Citrobacter, or Morganella species). Nonfermenters such as Pseudomonas aeruginosa, gram-positive cocci such as staphylococci and enterococci, and Candida species may also play an important role. The microbial spectrum is likely to differ over time and from one institution to the other. To follow the spectrum and development of antibiotic resistance, each ICU has to update its own surveillance analyses ( Table 113.1 , Fig. 113.1 ).

TABLE 113.1
Bacterial Spectrum of Healthcare–Associated Uropathogens (≥2%) From Distinct Surveillance Studies
Name of Study SENTRY SENTRY SENTRY ESGNI-003 GPIU-Study
Regions of the world North America Latin America Europe Europe Global
Year of surveillance 2000 2000 2000 2000 2003–2010
Type of surveillance Longitudinal Longitudinal Longitudinal Cross-section Cross-section
Origin of samples Microbiology laboratories Microbiology laboratories Microbiology laboratories Different departments in the hospital Urology departments
Number of pathogens n = 1466 n = 531 n = 783 n = 607 n = 1371
SPECIES, %
Escherichia coli 43% 60% 46% 36% 40%
Klebsiella spp. 12% 12% 9% 8% 11%
Pseudomonas spp. 7% 6% 9% 7% 11%
Proteus spp. 6% 7% 10% 8% 6%
Enterobacter spp. 3% 4% 4% 4% 5%
Citrobacter spp. 4% 2% 2% 2% n.r.
Enterococcus spp. 16% 4% 13% 16% 12%
Staphylococcus spp. 6% 3% 3% 4% 6%
RESISTANCE RATES OF ANTIBIOTICS FOR THE TOTAL BACTERIAL SPECTRUM TESTED, %
Ampicillin 59% [e] 62% [e] 65% [e] 66% [a] n.r.
Ampicillin + BLI 31% [e] 36% [e] 36% [e] 29% [a] 53%
TMP/SMZ 43% [e] 38% [e] 48% [e] 32% [a] 53%
Ciprofloxacin 29% [e] 32% [e] 29% [e] 17% [b] 51%
Gentamicin n.r. n.r. n.r. 18% 42%
Ceftazidime n.r. n.r. n.r. 13% [c] 38%
Amikacin n.r. n.r. n.r. 19% [c] n.r.
Piperacillin/tazobactam n.r. n.r. n.r. n.r. 30%
Imipenem n.r. n.r. n.r. 14% [c] 10%
Vancomycin n.r. n.r. n.r. 1% [d] n.r.

BLI, Beta-lactamase inhibitor; n.r., not reported; TMP/SMZ, trimethoprim-sulfamethoxazole.

a Gram-negative bacteria excluding Pseudomonas aeruginosa .

b Gram-negative bacteria.

c P. aeruginosa .

d Enterococci.

e E. coli, Klebsiella spp., P. aeruginosa , enterococci.

Fig. 113.1, Global and Regional Resistance Rates of the Total Bacterial Spectrum from Healthcare–Associated UTI. 7

Epidemiology

The Extended Prevalence of Infection in Intensive Care (EPIC II) study revealed that 51% of patients were infected on the study day and that 71% of all patients were receiving antibiotics. The most frequent types of ICU-acquired infections with their total occurrence were respiratory tract infections, 63.5%; abdominal infections, 19.6%; bloodstream infections, 15.1%; and renal or UTIs, 14.3%. The true incidence of UTI, however, may be even higher if more meticulously looked for. In a prospective study specifically evaluating nosocomial UTI, nosocomial UTIs accounted for 28% of nosocomial infections, lower respiratory tract infections for 21%, pneumonia for 12%, and bloodstream infections for 11%. The rates of urinary catheter–associated UTIs varied between 4.2% (symptomatic UTI) and 14.0% (asymptomatic UTI), which shows that asymptomatic bacteriuria is frequent in ICU patients, although symptoms of UTIs in intensive care patients are frequently difficult to assess. In the global one-day point prevalence study in urologic hospitalized patients (GPIU study), asymptomatic bacteriuria accounted for 27% of healthcare–associated (HA) UTIs (HAUTIs), followed by cystitis (26%), pyelonephritis (20%), urosepsis (11%), and other urogenital infections (16%), showing that HAUTI is present in high frequency in certain patient groups. In a recent infection control program HAUTI caused by indwelling urinary catheters (CAUTI) rates were assessed in ICUs in order to prevent CAUTI by educational means. Before the intervention, the CAUTI rate in ICU patients was 2.48 CAUTIs/1000 catheter days. In non-ICUs the CAUTI rate was 2.28/1000 catheter days.

UTIs in the ICU are divided into two groups:

  • 1.

    UTIs with nonurologic complicating causes: diabetes mellitus, renal insufficiency, immunodeficiency, infectious foci contiguous to the urogenital tract, or trauma patients

  • 2.

    UTIs with urologic complicating causes: renal transplantation, neurogenic bladder dysfunction, procedures in the urogenital tract, urinary stones or foreign bodies in the urogenital tract (e.g., CAUTI)

In UTIs with primary nonurologic complicating causes, antimicrobial therapy is generally sufficient. However, in UTIs with primary urologic causes, the complicating factors must be identified and treated. In such cases, antimicrobial therapy is only one component of the treatment.

Urinary tract infections with nonurologic complicating causes

Individuals with diabetes are at higher risk of UTIs. , Increased susceptibility in patients with diabetes is positively associated with the increased duration and severity of diabetes as a result of impaired granulocyte function, decreased excretion of the Tamm-Horsfall protein, low levels of interleukin (IL)-6 and IL-8 in the urine that lead to lower “cidality” of the urine, and altered microflora in the genital region. Furthermore, diabetic cystopathy and nephropathy may be complicating factors in the urinary tract. In addition to antibiotics, treatment must address the metabolic situation. In pyelonephritis, usually a switch to insulin or insulin-analogous therapy is necessary.

The place of immunosuppression per se in the development of UTI remains unresolved. Patients with end-stage renal failure are generally not particularly susceptible to the usual gram-negative urinary pathogens, although they may acquire unusual and granulomatous infections. Patients have evidence of reduced cellular and humoral immunity. However, the situation is a little clearer in male patients with human immunodeficiency virus (HIV) and AIDS, where there is a close relationship between CD4 counts and the risk of bacteriuria, particularly in those whose counts are less than 200 cells/mL.

Pathogens may be translocated into the urinary tract from contiguous infectious foci (e.g., appendicitis, sigmoid diverticulitis, or translocation by ileus). Symptoms and localization of pain can be misleading and may delay the diagnosis. Operations or trauma may cause hypothermia, tissue hypoxia, and hemodynamic alterations that result in kidney dysfunction and impaired mucosal perfusion. The use of latex catheters in these critical situations (e.g., operations with heart-lung machine) can also lead to urethral strictures. Silicone catheters or suprapubic catheters are recommended in these patients. Suprapubic catheters cannot prevent UTIs. They can, however, lower the rate of UTIs from 40% to 18%.

Urinary tract infections with urologic complicating causes

Patients show a high risk of developing bacteriuria after renal transplantation, threatening clinical outcomes for both the patient and transplant. Early infections (up to 3 months after transplantation) are differentiated from late infections (more than 3 months after transplantation). Early infections may present with no symptoms. In this phase, occult bacteremia (60% of bacteremias after renal transplantation originate from the urinary tract), allograft dysfunction, and recurrent UTIs after antibiotic therapy are frequently seen. Sometimes, it can be quite difficult to distinguish rejection from infection. Patients must also be investigated for surgical complications.

UTIs caused by Candida species are frequently asymptomatic. There is, however, a risk of obstructive fungal balls leading to candidemia or invasion of the anastomosis in renal transplant recipients. Asymptomatic candiduria should therefore be treated in these patients. Urine transport disturbances (e.g., from an obstructive ureteral stone) require specific urologic therapy such as percutaneous nephrostomy or stenting. In case of bladder obstruction, an indwelling urinary catheter (suprapubic or transurethral) will be the primary therapy in the ICU. Long-term indwelling catheters (more than 30 days) are associated with a selected microbial spectrum of difficult-to-treat uropathogens (e.g., Providencia spp., Proteus spp., or Pseudomonas spp.). After initiation of antimicrobial therapy, the catheter should be replaced to remove the biofilm material.

Pathophysiology

UTIs generally occur from organisms invading the urinary tract via the urethra. Pathogens originate from endogenous or exogenous nosocomial flora. Hematogenous spread to the urinary tract is rare.

In uncomplicated UTIs, pathogens need to have specific virulence factors enabling them to initiate an infection after invasion of the urinary tract. The medical conditions of an ICU patient may weaken physiologic barriers and defenses, thus facilitating the entry of pathogens. In addition, the nosocomial environment in the ICU, including antibiotic pressure and decreased supply of oxygen or nutrients (e.g., iron) to tissues, can select pathogens with specific resistance patterns. A general adaptation strategy is the formation of hypermutator strains, which show 100- to 1000-fold increased mutation frequencies, enabling the pathogens to rapidly adapt to challenging environments and thus develop effective mechanisms for antibiotic resistance. ,

An important mechanism contributing to UTI is the formation of biofilms, which are associated with the increased number of biomaterials used in medical practice. Biofilm infections develop not only around foreign bodies such as urinary catheters or stents but also in urinary stones, scarred or necrotic tissue, obstructive uropathies, or even chronic bacterial prostatitis. A biofilm has been defined as an accumulation of microorganisms and their extracellular products forming a structured community on a surface. The formation of a biofilm generally consists of three steps:

  • 1.

    Deposition of a host conditioning film

  • 2.

    Attachment of microorganisms followed by microbial adhesion and anchorage to the surface by exopolymer production

  • 3.

    Growth, multiplication, and dissemination of the organisms

The basic structural unit of a biofilm is a microcolony—that is, a discrete matrix-enclosed community consisting of bacteria of one or more species. The biofilm is usually built up of three layers , :

  • 1.

    Linking film that attaches to the surface of a tissue or biomaterial

  • 2.

    Base film of compact microorganisms

  • 3.

    Surface film as an outer layer, where planktonic organisms can be released to float freely and spread on the surface

Bacteria within biofilms differ both in behavior and phenotypic form from the planktonic, free-floating bacteria. The failure of antimicrobial agents to treat biofilms has been attributed to a variety of mechanisms:

  • Organisms encapsulated in biofilms grow more slowly than planktonic ones, probably because encapsulated bacteria have a decreased nutrient and oxygen supply, leading to a decreased metabolic rate and antimicrobial susceptibility. This may select a less susceptible genotype, forming a resistant population. Furthermore, antimicrobial binding proteins are poorly expressed in these slow-growing bacteria.

  • The biofilm matrix delays or impedes the diffusion of antibiotic molecules into the deeper layer of the film (extrinsic resistance).

  • Bacteria within the biofilm are phenotypically so different from their planktonic counterparts that antimicrobial agents fail to eradicate them. Bacteria within a biofilm activate many genes that alter the cell envelope and molecular targets by altering the susceptibility to antimicrobial agents (intrinsic resistance). These phenotypic changes are likely to play a more important role in the development of antimicrobial resistance than external resistance (biofilm matrix, glycocalyx).

  • Bacteria within a biofilm can sense the external environment, communicate with each other, and transfer genetic information and plasmids within biofilms.

  • Bacteria in biofilms can usually survive antibacterial concentrations 100–150 times higher than those needed to kill planktonic bacteria of the same species.

Antimicrobial treatment can be effective in only “young” biofilms (<24 hours). At present, combination therapy with fluoroquinolones and macrolides or fosfomycin seems to be most effective against biofilm infections. During an acute febrile phase of biofilm infection, antimicrobial therapy is essential and can be effective because the planktonic bacteria are responsible for the febrile reactions and not the bacteria covered in the biofilm. However, to eradicate pathogens from the biofilm, the biofilm itself has to be removed (e.g., catheter change or extraction of infectious stones).

Diagnosis

Medical history and physical examination

Sedated intubated patients are often difficult to evaluate regarding their signs and symptoms of UTIs. The patient or a family member should be asked about previous episodes of UTIs and urologic diseases (e.g., stones or tumors) or operations.

The physical examination should include inspection and palpation of the costophrenic area, lower abdomen, pubic region, inguinal lymph nodes, and genitals and a digital transvaginal or transrectal examination. Ultrasound is an important diagnostic device, and its use should be frequently considered because of the close proximity of the urogenital organs to the intestine, spleen, liver, pancreas, gallbladder, ovary, or uterus.

Urinary examinations

Urine specimens in ICU patients are almost exclusively collected from catheters. Because urine from catheters has to be collected into a closed system, the urine specimen should be taken from the puncture site at the catheter after disinfection, without opening the closed system. There are different complementary methods for laboratory examination of the urine specimen.

Dipstick test

The dipstick test is performed with undiluted urine and investigates the following infection-related parameters :

  • pH: An alkaline urine (pH >8.0) points to urease-producing organisms such as Proteus or Providencia spp. and is associated with magnesium-ammonium-phosphate stones.

  • Nitrate: Most Enterobacteriaceae harbor a nitrate reductase that reduces nitrate to nitrite. Some common uropathogens such as Enterococcus and Staphylococcus lack nitrate reductase and will therefore not be detected using this parameter, independent of their urinary concentration. The positive detection of nitrate requires its inclusion in the patient’s diet.

  • Leukocytes (positive leukocyte esterase): Granulocytes are the most frequently detected leukocytes in the urine of UTI patients. Macrophages appear fairly often in patients with UTIs, but their significance remains unknown.

  • Erythrocytes (positive hemoglobin): Hematuria remains a major sign of urinary tract and renal disease.

  • Specific gravity/osmolality (degree of urine dilution).

  • Protein: Total protein in urine is a mixture of high- and low-molecular-weight plasma proteins from the kidney and urinary tract or bacteria.

  • Glucose (metabolic condition of the patient).

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