Vincent T. Andriole

BACTERIAL URINARY TRACT INFECTIONS IN DIABETES

Diabetes mellitus has a number of long-term effects on the genitourinary system. These effects predispose to bacterial urinary tract infections in the patient with diabetes mellitus. Bacteriuria is more common in diabetic women than in nondiabetic women because of a combination of host and local risk factors. Upper tract infection complications are also more common in this group. Diabetic patients are at higher risk for intrarenal abscess, with a spectrum of disease ranging from acute focal bacterial pyelonephritis to renal corticomedullary abscess, to the renal carbuncle. A number of uncommon complicated urinary tract infection complications occur more frequently in diabetics, such as emphysematous pyelonephritis and emphysematous pyelitis. Because of the frequency and severity of urinary tract infection in diabetic patients, prompt diagnosis and early therapy is warranted. A plain abdominal radiograph is recommended as a minimum radiographic screening tool in the patient with diabetes presenting with systemic signs of urinary tract infection. Ultrasonography or further radiographic studies such as CT scanning may also be warranted, depending on the clinical picture, to identify upper urinary tract complications early for appropriate intervention.

The quinolones: past, present, and future.

The quinolone class of antimicrobial agents has generated considerable interest since its discovery >40 years ago. Substantial progress has been made in our understanding of the molecular mechanisms of the action of quinolones against pathogenic bacteria, the induction of resistance to quinolones in these organisms, and the potential of each quinolone compound to induce toxicity in treated patients. Here, these key discoveries are reviewed; the present indications approved by regulatory agencies are described in detail, with comments on adverse events caused by quinolones in treated patients; and speculation about the future of the quinolones is proffered, even though their future is difficult to predict, because many factors may affect their clinical usefulness. However, the emergence of bacterial resistance to the quinolones is a major factor that will determine the future clinical effectiveness of these agents, so that intense investigation of mechanisms to either prevent or curtail resistance to quinolones is of prime importance to their future.

Urinary tract infection in adults: research priorities and strategies

Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies.

Gram-negative bacillary meningitis☆

All cases of unusual types of gram-negative bacillary meningitis in a university hospital over a five year period were retrospectively analyzed. These patients comprised 4.2 per cent of cases of bacterial meningitis among all patients, 69 per cent of neurosurgical cases and 42 per cent of neonatal cases. The over-all mortality was 40.3 per cent. The two most common bacterial isolates were Escherichia coli in patients younger than one year and Klebsiella species in patients above that age. Infection may be acquired at birth or at the time of surgery, or may be secondary to spread of infection from other body sites. Gram-negative bacillary meningitis is a nosocomial infection and this diagnosis should be suspected in patients in whom central nervous system infection develops in the hospital.

RENAL AND PERIRENAL ABSCESSES

Our knowledge of the spectrum of renal abscesses has evolved as a result of more sensitive radiologic techniques. The classification of intrarenal abscesses currently includes acute focal bacterial nephritis, acute multifocal bacterial nephritis, renal cortical abscess, renal corticomedullary abscess, and xanthogranulomatous pyelonephritis. The clinical presentation of these entities does not differentiate them, however, and various radiographic studies are helpful in making the diagnosis. The intrarenal abscess is usually treated successfully with antibiotic therapy alone. Antistaphylococcal therapy is indicated for the renal cortical abscess, whereas therapy directed against the common gram-negative uropathogens is indicated for most of the other entities. The perinephric abscess is often an elusive diagnosis, has a more serious prognosis, and is more difficult to treat. Drainage of the abscess and sometimes partial or complete nephrectomy, in addition to antibiotic therapy, are required for resolution.

Epidemiology, Natural History, and Management of Urinary Tract Infections in Pregnancy

The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic UTIs in women with bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic UTI and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery.

The Future of the Quinolones

This review emphasises the advances in the development of newer quinolones: their broader antimicrobial activity particularly their increased activity against Pneumococcus and anaerobes; their longer half-life and tissue penetration including activity in cerebrospinal fluid; and their excellent efficacy in respiratory, intra-abdominal, pelvic, and skin and soft tissue infections. Also, considerable progress has been made in our understanding of the development of bacterial resistance to the newer quinolones. Additional advances in quinolone development are likely to provide better compounds for clinical use.

Efficacies of Two New Antifungal Agents, the Triazole Ravuconazole and the Echinocandin LY-303366, in an Experimental Model of Invasive Aspergillosis

ABSTRACT The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal or sublethal challenge. Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis. Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of either drug was seen after 6 days of treatment. Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B. Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.

Cryptococcal infection of the central nervous system.

The pathogenesis, clinical signs and symptoms, laboratory manifestations, and laboratory diagnosis of cryptococcal infection of the central nervous system are reviewed, as well as the interaction between the organism and the immune system of the host. In addition, based on our own experience and that of others, the therapy and prognosis of cryptococcal meningitis are discussed.

Development of Meningitis During Cephalothin Therapy

Abstract Five patients developed meningitis while receiving cephalothin. Three other cases of this complication have been previously reported. Patients with bacteremia and debilitating chronic dise...