Initially, antibiotic therapy must be broad-spectrum to cover multiple organisms and drug resistance.
Infections are a serious complication and leading cause of death in debilitated patients, including those with cancer, immunosuppression (e.g., transplantation or AIDS patients), diabetes, chronic renal failure, severe neurologic conditions such as Parkinsonism or spinal cord injury, and the elderly.1
For example, approximately 50% of patients dying from solid tumors who had a complete postmortem examination died from infection. Since debilitating factors frequently coexist, the impact is frequently compounded.1
Urinary tract infections are among the most common infections in the debilitated population in large part because many of the patients have urinary catheters. In fact, catheter-associated bacteriuria (CAB) occurs at a rate of 5% per day,2,3 and although it does not require treatment, conversion to symptomatic events with fever and upper tract disease is common.
Since these infections are usually acquired in a health-care setting where antimicrobial use is pervasive, bacterial virulence and antimicrobial resistance is increased. Because these patients are usually on multiple medications, drug-drug interactions that reduce agent efficacy and increase associated side effects are common. Corticosteroids, for example, which are frequently used to treat these comorbidities, enhance the susceptibility to infection.1
Lastly, structural or functional abnormalities of the urinary tract are common in debilitated patients. Urinary obstruction and dehydration lead to renal failure and reduced ability of the antimicrobials to concentrate within the urinary tract, thus diminishing their efficacy. Therefore, careful assessment, diagnosis and management are essential to maximize efficacy and reduce morbidity in debilitated patients with urinary tract infections.
Uncomplicated UTIs, in patients who are non-debilitated, are usually ascending events caused by
bacteria that migrate through the urethra into the bladder; instrumentation is not associated in these instances. In debilitated patients, the urinary tract is frequently compromised due to aging and acquired effects of obstruction, for example, from stones or enlargement of the prostate gland or BPH.
In addition, catheterization bypasses the normal defense systems, allowing easier bacterial access to the urinary tract. These catheters also provide a convenient nidus for bacteria that can be incorporated within the catheter’s biofilms where they are protected from antimicrobials.4
Recent evidence suggests that bacteria also may be incorporated into intracellular pods within the bladder where they become surrounded by a biofilm.4 Urinary tract levels of antimicrobials effective against superficial bacteria may not as effectively treat these bacteria.4 When the upper tract is compromised by decreased renal function and/or other comorbidities such as severe diabetes, infections can become much more severe.
Pyelonephritis can progress to intrarenal and perirenal abscesses with mortality rates in excess of 50%.5 These infections are frequently complex due to multiple bacteria and yeast. In addition, the bacteria frequently show multiple drug resistance because of the patients’ exposure to antimicrobials and the fact that the bacteria are usually acquired within a hospital or nursing home setting.6
Multiple drug resistance is usually associated with extrachromosomal transfer of plasmids.7,8 These plasmids incorporate not only resistance to the drug the patient is receiving but also multiple agents that share this plasmid-mediated resistant capability. These include broad-spectrum and beta lactams, aminoglycosides, and sulfonamides. Only the quinolones are not associated with plasmid-mediated resistance.