A Practical Approach to Diagnosing and Treating Urinary Tract Infections in Adults

dispose to bacteremia with group B streptococcus and Clostridium septicum, and many authors recommend a search for an underlying colonic malignancy when these organisms are isolated from blood culture specimensAs shown in Table 2, a variety of malignancies,both solid and hematologic, have been reported in association with group G streptococcal infections, usually bacteremia or septic arthritis. The clinician is then faced with the most cost-effective and efficient work-up of these patients in a manner not to overlook an underlying malignancy. There are no formal recommendations in the literature as to a standard evaluation for excluding malignancy in these patients. However, it is imperative to remember that the most important element is a thorough history and physical examination, paying particular attention to lymph node enlargement, liver enlargement or abdominal masses, prostate abnormalities, breast masses, and fecal occult blood testing. Patients with group G streptococcal bacteremia without an obvious source also should have a complete blood count and differential as well as liver chemistries. Other simple tests to consider are prostate spe-

cific antigen, mammogram, and gastrointestinal endoscopy. Computed tomography probably should not be done in every case but reserved for patients who have abnormalities on physical examination or basic laboratory studies.

Treatment Treatment of infections due to group G streptococci entails proper antimicrobial selection as well as drainage of abscessesand joint spaces in the case of septic arthritis. These organisms are typically very sensitive to penicillin G and other beta-&am antibiotics. Erythromycin, clindamycin, and vancornycin are alternatives in the penicillin-allergic patients. The addition of an aminoglycoside should be considered in serious infections such as endocarditis, septic arthritis, or treatment failures. The combination of a beta-lactam and an aminoglycoside may be synergistic in these circumstances.

Bibliography Gallis HA: Streptococcus. In: Joklik WK, Wiiett HP, Amos DB, Wilfert CM, eds. Zinsser Microbiology. 19th ed. East Norwalk, Connecticut: Appleton and Lange, 1988, pp. 365.

Gill MV, Cunha BA: Group G streptococci: a review. Infect Dis Clin Prac 4: 162166.1995. Jaffe R, Newman JH: Group G streptoccccus arthritis associated with adenocarcinoma of the colon. Del Med J 57:301-302.1985. Karlawish JHTz Group G streptococcal bacteremia caused by an asymptomatic esophageal carcinoma in an elderly man. South Med J 87:667*8,1994. Marinella MA: Group G streptococcal septic arthritis of an interphalangeal joint clin Exp Rheum, In press. Marinella MA: Thumb cellulitis due to group G streptococcus. J Am Geritr Sot 44:887-888,1996. Vartian C, Lemer PI, Shlaes DM, Gopalakrishna KV: Infections due to Lancefield group G streptococci. Medicine 64: 75f&1985. Vartivarian S, Bodey GP: Infections associated with malignancy. In: Gorbach SL, Bartlett JG. Blacklow NR, eds. Infectious Diiases. Philadelphia: W.B. Saunders Company, 1992, pp. 103-1039. Watsky KL. Kollisch N, Densen P: Group G streptococcal bacteremia: the clinical experience at Boston University Medical Center and a critical review of the literature. ArchIntern Med 145:58-61.1985. Yeavasis-Lupenko E, Gill V, Cunha BA: Group G streptococcal cellulitis and bacteremia. Heart Lung 24:89-90,1995.

A Practical Approach to Diagnosing and Treating Urinary Tract Infections in Adults Charles W. Stratton, MD Vanakrbilt University School of Medicine Nashville, Tennessee 37215

Introduction Urinary tract infections (UTIs) continue to be a commonly encountered clinical problem. For example, UTIs involve more than seven million outpatient visits as well as over one million hospitalizations each year in the United States. Fortunately, an understanding of the pathogenesis and epidemiology of these infections readily allows a costeffective approach to the diagnosis and therapy of UTI’S.

Definitions The commonly used term “UTI” deAntimicmbics

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scribes a diverse range of urological infections that cannot be dealt with in a uniform diagnostic and therapeutic manner despite the temptation to do so. Attempts to apply the same diagnostic or therapeutic approach to each of these urinary tract infections results in either increased cost or decreased quality of care. Instead, UTIs must be categorized along with a prudent risk assessment in order to allow the clinician to make logical and cost-effective choices among various diagnostic and therapeutic optiOllS.

Pathogenesis The pathogenesis of UTIs involves a number of important factors that influence the epidemiology of UTIs. These Q 19% Elsevier

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include gender-related anatomic differences in the urinary tracts. The femaleto-male ratio of 8: 1 for acute cystitis is largely due to the fact that women have a relatively short urethra that is exposed to a microorganism-rich environment. Exposure to microorganisms leads to colonization of the periurethral glands in women that may later result in entry of these organisms into the bladder due to mechanical events such as sexual intercourse. Colonization, moreover, is related to the presence of specific receptors on the cell surfaces of certain uropathogens such as Escherichiu coli as well as to the presence of reciprocal receptors on the urogenital cells. Because the latter are associated with a similar h&o-blood secreter status, a ge1069417xB6/w..00

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netic basis for recurrent cystitis is possible. Categorization There are many classification schemes for UTIs, such as those based upon the anatomic location (upper tract vs. lower tract) or those based upon the complexity (complicated vs. uncomplicated). Most of these schemes have had a minimal effect on the diagnostic or therapeutic approach to UTIs as the acute presentation of epidemiologically related groups of patients seen by practicing clinicians does not fit well into these schemes. Stamm, however, has noted that most UTIs in adults are acute symptomatic and fall into one of three categories: i) acute uncomplicated cystitis in women, ii) acute uncomplicated pyelonephritis in women and iii) acute complicated UTIs in men and women. The ability to place a patient into one of these three groups allows the clinician to predict the most likely uropathogen and to initiate empirical therapy with an appropriate antimicrobial agent. Moreover, the need for urine culture and sensitivity as well as other diagnostic studies is dictated by the category in which the patient is placed. Acute Uncomplicated Cystitis in Women Acute uncomplicated cystitis is most commonly seen in women, usually of child-bearing age. Of the seven million outpatient visits per year, 60-70% of these are young women with acute cystitis. The onset of symptoms may be related to sexual intercourse, which can introduce into the bladder bacteria that have colonized the anterior urethra or vaginal introitus. Other risk factors include the use of a diaphragm and/or a spermicide, delayed postcoital micturition, and a history of a recent UTI. Frequently reported symptoms include dysuria, frequency and urgency of urination. Discomfort in the suprapubic, pelvic, or low back area may be a complaint, as may a slight fever. Common signs are hematuria (30%) and suprapubit tenderness (10%); both are relatively specific findings for cystitis. The etiologic agents in young women with acute uncomplicated cystitis are few in number and include E. 38

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coli in 80% Staphylococcus saprophyticur in ?I-15%, and other microorganisms such as Klebsiella species or Proteus mirabilis in the remainder. The

onset of menopause is for some unknown reason associated with the disap pearance of S. saprophydcus as a common pathogen in women with acute cystitis. The key elements of the diagnostic workup for uncomplicated cystitis in women are a detailed history taking, a thorough physical examination (to include a pelvic examination if the diagnosis is at all in doubt), and appropriate laboratory tests. The history should include the following assessment of risk factors: i) First episode vs. recent episode or multiple episodes. Previous episodes of UTIs increase the accuracy of the patient’s self-assessment. In addition, previous episodes raise the possibility of resistant or unusual uropathogen. ii) Association with sexual intercourse, use of diaphragm and/or spermicide, or use of feminine hygiene products. These factors not only predispose to UTIs, but are also important patient education issues and should be explained to the patient. iii) Other risk factors for infection in general such as diabetes mellitus, corticosteroid use, HIV infection, etc. These factors can complicate an otherwise uncomplicated UTI. The physical examination is important for the exclusion of vaginal conditions, such as vaginitis and vulvar vestibulitis, that can mimic cystitis. The pelvic exam may be useful for confirming the clinical impression of cystitis in those women (-10%) who have suprapubic tenderness on pelvic examination. The laboratory tests used in some combination to diagnose acute uncomplicated cystitis in women include the following: Microscopic urinalysis Microscopic urinalysis allows identification of abnormal cellular constituents in the urine and may reveal microorganisms. Urinalysis of an unspun urine specimen is more useful than that of a spun specimen for detecting significant leukocyturia. In unspun urine specimens, more than 10 leuko0 19% Elsevicr

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cytes per cubic millimeter represents pyuria. Women with cystitis generally have pyuria with (-30%) or without hematuria. Pyuria without hematuria is seen with urethritis but is rare with vaginitis unless the urine has become contaminated with vaginal secretions. Leukocyte esterase dipstick test Leukocyte esterases are membranebound enzymes that are not present in acellular urine, but are present whenever leukocytes are present. Even if leukocytes lyse after the urine is allowed to sit for several hours, these esterases are still present and produce a blue chemical reaction on dipstick. The sensitivity of this test for identifying more than 5 leukocytes per cubic millimeter is -95% and the specificity is 70%. Nitrite dipstick test Most uropathogens, except S. suprophyticus and Enterococcus species, reduce urinary nitrate to nitrites which can be detected by a chemical reaction on a dipstick. Because uropathogens must be in the urine for at least 6 hours to produce a measurable nitrite level, it is best to test the first voided urine specimen in the morning. The sensitivity for a first voided specimen is -8O%, but falls to as low as 30% for subsequent urine specimens. The specificity, however, is greater than 90%. Urine culture Urine cultures accomplish three objectives: i) detection of the presence of bacteriuria, ii) estimation of the density of the presumed uropathogen, and iii) identification of the uropathogen as well as its susceptibility to antimicrobial agents. Urine microscopy can accomplish the first and second objectives provided the colony count is equal to or greater than 100,000 per ml. Only culture can accomplish the last objective, identification and susceptibility testing. The density of the presumed uropathogen previously has been considered diagnostic of urinary tract infection when the colony count for an aerobic Gramnegative bacillus is equal to or greater than 100,000 per ml (recent information suggests that infection can be seen with colony counts as low as 100 per ml). Colony counts of Gram-positives and yeasts have been correlated with infecAntimicmbics

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tions. Counts obtained when the patient has been on antibiotics or has a foley catheter are meaningless. As long as the prevalent uropathogens in acute uncomplicated cystitis continue to be E. coli and S. saprophyticus and the susceptibility patterns of these two microorganisms remains predictable, a “cultureless” workup for acute uncomplicated cystitis is reasonable. Urine cultures should be done whenever there is diagnostic uncertainty, suspected upper urinary tract infection, more than three episodes of cystitis per year, asymptomatic pyuria detected in a young woman (pregnant or not) on routine urinalysis, and therapeutic failure. The same situations that require a urine culture may necessitate referral to a urologist, depending on the particular restrictions of a managed care plan (if any). These cultures are usually obtained using the mid-stream-voiding method unless this is not possible in which case a straight catheterization or a supra-pubic needle aspiration is done. The latter supra-pubic needle aspiration is most often used for children.

fluoroquinolones, as such use has caused increasing resistance to these agents in E. cob.

Acute Uncomplicated Pyelonephritis in Women Localization studies have demonstrated that up to 30% of women with the clinical presentation of cystitis may have subclinical upper urinary tract involvement. Many attempts have been made to identify which patients have upper urinary tract involvement. The presence of white blood cell casts on urinalysis is the only rapid way to do this; unfortunately, this method is not very sensitive. A sedimentation rate or a C-reactive protein, when elevated, strongly suggests the possibility of upper urinary tract involement. Mitigating circumstances which suggest the possibility of upper urinary tract infection include diabetes, symptoms for greater than 7 days, use of diaphragm, pregnancy, age greater than 65, and recent urinary tract infection. 1) Women with symptomatic involvement of their upper urinary tract are defined as having acute pyelonephritis. Their symptoms may be similar to those seen with cystitis except for the possible addition of fever, chills, and flank pain. When patients with acute pyelonephritis have symptoms and signs of sepsis such as high fever, mental confusion,a nd hypotension: the term “urosepsis” is used. As mentioned earlier, microscopic urinalysis on a fresh urine specimen may reveal white blood cell casts which confirms upper tract involvement. In this setting, urine cultures should be obtained. These women may be more difficult to sterilize than those with only cystitis, and a 10-14 day course according to susceptibility testing of therapy should be given. The therapy of acute uncomplicated pyelonephritis in women who have mild to moderate illness with no nausea or vomiting is the same outpatient therapy with oral antimicrobial agents as indicated for cystitis except that therapy should be continued for l&l4 days For severe illness such as urosepsis or pyelonephritis in pregnancy, hospitalization and parenteral therapy is required.

Therapy

Therapy of acute uncomplicated cystitis should result in sterilization of the urine during the course of antimicrobial therapy and for at least 3 days following therapy. Selection of an appropriate antimicrobial agent involves a number of important considerations. The first of these is the local prevalence of resistance in E. coli. Another is the presence or absence of allergies in the patient. For women with acute uncomplicated cystitis who have no sulfa allergies, and where resistance to trimethoprim-sulfamethoxazole is not found, this agent given for 3 days is effective and inexpensive. There have been reports of uropathogens becoming resistant to trimethoprim-sulfamethoxazole, and clinicians prescribing this antimicrobial combination should know the resistance rate in their community. Alternatively, a 7-day course of nitrofurantoin monohydrate/macrocrystals is a reasonable choice as this agent remains active against E. coli despite many decades of use. A class of antimicrobial agents that should not be used in acute uncomplieated cystitis in young women is the Antimicmbics

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Complicated Urinary Tract Infection in Men and Women. Complicated urinary tract infections in men and women are generally seen in patients who have an abnormal urinary tract. Anatomical abnormalities that lead to stasis, such as prostatic enlargement in men, pelvic floor relaxation in women, neurogenic bladder in paraplegics, etc., are among the most important predisposing factors. Many of these factors, as expected, are found in elderly patients. The clinical spectrum of these complicated urinary tract infections spans that of cystitis to urosepsis. Unlike the narrow spectrum of uropathogens seen in uncomplicated infections, a wide variety of microorganisms can cause complicated infections, many of which may have unusual susceptibility patterns, or be resistant. Urine cultures are required, and the results most often dictate the antimicrobial therapy. A referral to a urologist for invasive studies may be needed, and is always indicated in men. A urological condition often included in the uncomplicated urinary tract infection category is asymptomatic bacteriuria with or without the presence of an indwelling urinary catheter. Chronic asymptomatic bacteriuria and pyuria is universal in patients who have chronic indwelling urinary catheters. The diagnosis of urinary tract infection in patients with indwelling urinary catheters is made on clinical findings such as fever and supra-pubic or flank pain/tenderness. When cultures are obtained, be sure to request that all isolates are identified and have susceptibility testing performed. A common problem leading to asymptomatic bacteriuria is pregnancy. Pregnant women should be screened for bacteriuria during their pregnancy and treated if bacteriuria is found. Chronic conditions resulting in stasis such as prostatic hypertrophy and pelvic floor relaxation are common in the elderly who consequently have a high rate (>40%) of asymptomatic bacteriuria. The presence of this bacteriuria in the elderly, however, does not result in decreased life expectancy and need not be screened for nor treated except when urologic surgery is planned. 3069-417X/‘96/$0.00

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Bibliography Aguiar, J. M., Chacon, J. Canton. R., et al. The emergence of highly fluoroquinoloneresistant Esckrichiu cozi in eomnulnityscquired urinary traEt infections. (Letter) J. Antimicrob. Chemother. 29349-350, 1992. Alon, U., Davidai, G., Berant, M., et al. Five-year survey of changing patterns of susceptibility of bacterial uropathogens to trimethoprimsulfamethoxazole and other sntimicrobial agents. Antimicrob. Agents Chemother. 31:126-128.1987. Bartlett, R. C., Galen,R. S.predictivevalue of urine culture. Am. J. Clin. Pathol. 79756757.1983. Bonadio, M. Predictive value of urine microscopy in urinary tract infections. (Lctter) Nephron. 2498.1979. Boscia, J. A., Abrutyn, E., Kaye, D. Asymptomatic bacteriuria in elderly persons: Treat or do not treat? Ann. Intern. Med. 106:764-766,1987. Bmmerna, D. A., Adams, J. R, Pahams, R.. et al.seculartradsinratessndetiologyof nosommialurinarytractinfectitnsatatiwsity hospital. J. Ural. 150~41ti16,1993. Carroll. K. C., Hale, D. C.. VonBoerum, D. H., et al. Laboratory evaluation of urinary tract infktions in an ambulatory clinic. Am. J. Clin. Pathol. 101:10&103,1994. Chgue, J. E., Horan. M. A. Urine culture in the elderly: scientifically doubtful and practically useless? Lancct 344: 1035 1036.1994. Cox, C. E.. Lacy, S. S.. Hiian, F., Jr. The

urethra and its relationship to urinary tract infection. ll. The urethral flora of the female with recurrent urinary infection. J. Urol. 99~632438.1968. Jordan, P. A., Jravani. A., Richard, G. A., et al. Urinary tract infection caused by Staphylococcus saprophyticus. J. Jnfect. Dis. 142:51&515,1980. Kunin, C. M., White, L. V., Hua, T. H. A reassessment of the importance of lowcount bacteriuria in young women with urinary tract infection. Amr. Intern. Med. 119:454-460.1993. Kunin, C. M. The quantitative significance of bacteria in the unstained urine sediment N. Engl. J. Med. 265:589-590, l%l. McGsker, C. C., Fitzpatric, P. M. Nitrofurantoin mechanism of action and implications for resistance development in common uropathogens. J. Antimicrob Chemotha. 33:23-33,1994. Monzon. 0. T.. Ory, E. M., Dobscm, H. L., et al. A comparison of bacterial counts of the urine obtained by needle aspiration, catheterization, and midstream-voided methods. N. Engl. J. Med. 259:764-777, 1958. Pappas,P.G.L&omunyinthed&nosiiand managunmt of urinary tract infections. Med. Clin.North Am. 75:313-325.1991. Patton, J. P., Nash, D. B., Abrutyn, E Urinary tractinf~ economicconsidemtims. Med. Clin. North Am. 75:49%513,1991. Pfau, A., Sacks, T. The bacterial flora of the vaginal vestibule, urethra aud vagina in

the normal premenopausal woman. J. Urol. 118: 292-295,1977. Platt, R. Quantitative definition of bacteriuria. Am. J. Med 75(Suppl. 1 B): 44-52, 1983. Remis. R. S., Gurthwith. M. J., Gurthwith. D., Hargrett-Bean. N. T., Layde, P. M. Risk factors for urinary tract infection Am. J. Epidemiol. 126: 685-694,1987. Stamm. W. E.. Hooton. T. M. Management of urinary tract infections in adults. N. Engl. J. Med. 329:1328-1333, 1993. Stamm, W. E. Protocol for the diagnosis of urinary tract infection: reconsidering the criterion for significant bacteriuria. Urulogy 32:(Suppl.) c-12,1988. Stapleton, A., Nudelman. E., Clausen, H.. et al. Binding of uropathogenic Escherichiu coli R45 to glycolipids extracted from vaginal epitbelial cells is dependent on h&o-blood group secretor status. J. Clin. Inwzst. 90: %5-972,1992. Steen&erg, J., Bartels, E. D., Bay-Nielsen, H., et al. Epidemiology of urinary tract diseases in general practice. Br. Med. J. 4: 390-394,1969. Waters, W. E. Prevalence of symptoms of urinary tract infection in women. Br. J. Prev. SOL Med. 23: 26s266.1969. Woodwell, D. A. Office visits to urologists, United States, 1989-1990. National Center for Health Statistics, Centers for Disease Control, Advance Data No. 234, May, 1993.

Case Report

Endocarditis Caused by Actinobacillus actinomycetemcomitans Around the Native Aortic Valve Matilde Elfa Maite Celd6n MariaJoseAlCantara Gloria Royo HospitalGeneralUniversitariodeEl&e (Alicante).Spain

Imiul Eldin Yousef !kcci&~ I Microbiologfa y Cardiobgio HaspitalGeneralthiversitario deEkhe (Alicante).Spain

Actinobacillus actinomycetemcomitans is a slow-growing, Gram-negative coccokiIhls tJlat belongs to the HACEK group. of microorganisms. It is found in the mucous membrane of the 40

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mouth in U-60% of all healthy individuals and is principally associated with pcriodontitis and eudocarditis. It has also been implicated in infections of soft tissue, cerebral abscesses,empyema, pneumonia, thyroid abscesses, parotiditis, osteomyelitis, urinary tract infections, endophthalmitis, and arthritis. Endoca&k caused by Actinobacillus actinomycetemcomitans is not very li-equent and only appears in 1.1% of all prostbelic vahes and in 0.27% of all naturalvalves.Wepresenttbecaseofa patient affIictcd with endocarditis around the native aortic valve due to Actinobacillus actinomycetemcomitans. 8 19% Else&r

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Our patient is a 59-year-old male who was admitted to the hospital due to a U-kilo weight loss in 4 months together with asthenia, shivers and lumbar pain. His medical history included an episode of ischemic cardiopathy 10 years earlier, correctly treated high blood pressure, and a cerebrovascular event in the right cerebellum section of the brain. One month prior to admission the patient underwent a gash-oscopy and a colonoscopy. This patient’s lab work yielded the following values: hemoglobin 9.3 g/dl, platelets 18 1,ooo/mm3, leukocytes 7,400/mm3. and VSG 133 mm in the Antimicmbies

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