Aerococcus Urinae UTI 2000
Aerococcus Urinae UTI 2000
4
0095-1137/00/$04.00⫹0
Copyright © 2000, American Society for Microbiology. All Rights Reserved.
            Aerococcus urinae is a rarely reported pathogen, possibly due to difficulties in the identification of the
          organism. A. urinae is a gram-positive coccus that grows in pairs and clusters, produces alpha-hemolysis on
          blood agar, and is negative for catalase and pyrrolidonyl aminopeptidase. Some of these characteristics and its
          being absent from the databases of most commercial identification systems could allow A. urinae to be
          misidentified as a streptococcus, enterococcus, or staphylococcus. We report two cases of urinary tract infection
          (UTI) caused by A. urinae and characterize these isolates by morphology, biochemical testing, whole-cell fatty
          acid analysis, 16S rRNA gene sequencing, and antibiotic susceptibilities. Most patients infected with A. urinae
          are elderly males with predisposing conditions who present initially with UTI. Because A. urinae is resistant to
          sulfonamides, treatment could be inappropriate, with infections resulting in serious complications, including
          death. It is important for the clinician and the microbiologist to consider A. urinae a potential pathogen and
          proceed with thorough microbiological identification.
                       CASE REPORTS                                          with normal vital signs and a large, tender prostate on physical
                                                                             exam. Urinalysis revealed 4 to 6 WBCs/HPF, no bacteria, trace
   Case 1. An 80-year-old male with preexisting coronary artery              amounts of leukocyte esterase, and negative results for nitrites,
disease, left-sided hemiparesis (the residual effect of a stroke),           protein, ketones, bilirubin, and blood. He was diagnosed clin-
and multiinfarct dementia was admitted to the hospital for                   ically with prostatitis and treated with tetracycline due to a
altered mental status. The patient developed slowly worsening                history of ciprofloxacin allergy. The patient developed a rash
urinary symptoms, including nocturia and frequency, over the
3 weeks prior to admission.
   On admission the patient was afebrile with normal vital
                                                                                TABLE 1. Biochemical results of the present clinical isolates
signs. The physical examination was unremarkable except that                   compared with the literature values for A. urinae and A. viridans
a marked disorientation to place and time and a left-sided                             (adapted from references 1, 2, 4, 5, 6, and 7)
hemiparesis (the residual effect of a previous stroke) were
observed. Urinalysis showed white blood cells (WBCs) too                                                                            Result fora:
numerous to count, 8 red blood cells/high power field (HPF),                                  Test                   Present clinical
many bacteria, a specific gravity of 1.017, and a pH of 5.0, with                                                                       A. urinae   A. viridans
                                                                                                                         isolates
negative results for protein, ketones, and bilirubin. The patient
had a serum WBC count of 6.6 (64% neutrophils, 19% lym-                      Hydrolysis of:
                                                                               Hippurate                                    ⫹             ⫹            NA
phocytes, 9% monocytes, 7% eosinophils, and 1% basophils)                      Arginine                                     ⫺             ⫺            NA
and a hemoglobin and a hematocrit of 10.6 g/dl and 31.5%,                    Acid production from:
respectively. Serum chemistries including electrolytes, glucose,               Glucose                                      ⫹             ⫹            NA
liver, renal, and thyroid function tests were all reported as                  Sucrose                                      ⫹             ⫹            ⫹
normal. Chest X-ray was normal except for an elevated right                    Maltose                                      ⫺             ⫺            ⫹
hemidiaphragm. Computed tomogram of the head revealed a                        Sorbitol                                     ⫹             ⫹            ⫺
previous infarct in the distribution of the right middle cerebral              Lactose                                      ⫺             ⫺            ⫹
artery as well as hypodensity consistent with diffuse small ves-               Trehalose                                    ⫺             ⫺            ⫹
sel disease. The patient was treated empirically with intrave-                 Mannitol                                     ⫹             ⫹            V
                                                                               Inulin                                       ⫺             ⫺            NA
nous ciprofloxacin for presumed urinary tract infection (UTI).                 Starch                                       ⫺             NA           NA
Urine cultures grew ⬎105 CFU of Aerococcus urinae, the only                    Glycogen                                     ⫺             ⫺            NA
isolate, per ml. His urinary symptoms resolved and his mental                  Ribose                                       ⫹b            ⫹b           V
status improved by hospital day 3. The patient was discharged,                 L-Arabinose                                  ⫺             ⫺            NA
having had oral ciprofloxacin prescribed. Results of repeated                Enzyme production
urinalysis after discharge were normal.                                        -Glucosidase                                ⫺             ⫺            NA
   Case 2. A 58-year-old white male with adequately treated                    -Glucuronidase                              ⫹             ⫹            ⫺
hypothyroidism presented at the Veterans Affairs Medical                       -Galactosidase                              ⫺             ⫺            ⫹
Center outpatient clinic with several days of dysuria, increased               ␣-Galactosidase                              ⫺             ⫺            NA
                                                                               Alkaline phosphatase                         ⫺             ⫺            NA
urinary frequency, and nocturia. He was afebrile at the time,                  Leucine arylamidase                          ⫹             ⫹            ⫺
                                                                               Pyrrolidonyl aminopeptidase                  ⫺             ⫺            ⫹
                                                                               Urease                                       ⫺             NA           NA
  * Corresponding author. Mailing address: Pathology and Laboratory            Nitrite reductase                            ⫺             ⫺            NA
Medicine Service (113), Veterans Affairs Medical Center, 2002 Hol-
combe Blvd., Houston, TX 77030. Phone: (713) 794-7336. Fax: (713)             a
                                                                                  NA, not available; V, variable; ⫹, positive; ⫺, negative.
794-7657. E-mail: jillc@bcm.tmc.edu.                                          b
                                                                                  Acid production was slow.
                                                                      1703
1704       CASE REPORTS                                                                                                                                                                                                                                                                                                                   J. CLIN. MICROBIOL.
Endocarditis, death
                                                                                                                                                                                                                                                                                                  Endocarditis, death
                                   Present isolates
       Antibiotic                                                A.         A.
                             Disk
                           diffusion           E-testc         urinae    viridans
Recovered
Recovered
                                                                                                                                                                                                                                                                                                                        Recovered
                             testb
                                                                                                                                                                                                                                                                                                                                           Unknown
                                                                                                                                                                                                                                                              death
Penicillin G              S (40, 40)     S (0.016, 0.064)       S         R
                                                                                                                                                                                                                                                                                                                                                                                   PR, present report; M, male; F, female; CIP, ciprofloxacin; TET, tetracycline; TMP, trimethoprim; AMP, ampicillin; GEN, gentamicin; CXM, cefuroxime; SULFA, sulfamethizole.
Trimethoprim-             R (0, 0)       R (0, 0)               R         S
  sulfamethoxazole
Vancomycin                S (26, 25)     S (0.75, 0.75)         S         S
                                                                                                                                                                               Initial treatment
Ciprofloxacin             S (30, 30)     S (0.25, 0.25)         NA        NA
AMP, GEN
                                                                                                                                                                                                                                                                                                                        AMP, GEN
Gentamicin                R (0, 0)       ND                     R         S
                                                                                                                                                                                                                                                                                                                                           Unknown
                                                                                                                                                                                                                                                                                                  SULFA
Tetracycline              S (32, 32)     S (0.25, 0.5)          S         S
CXM
                                                                                                                                                                                                                                                                                TMP
                                                                                                                                                                                                                             TET
                                                                                                                                                                                                         CIP
                                                                                                                                                                                                                                                            CIP
  a
     S, susceptible; R, resistant; NA, not available; ND, not done.
  b
     Standard disks recommended by National Committee for Clinical Labora-
                                                                                    TABLE 3. Summary of clinical features of our two cases and previously reported casesa
tory Standards guidelines were used. Values in parentheses are inhibitory zone
sizes (in millimeters) for the isolates from cases 1 and 2 (in that order).
No sign of sepsis
                                                                                                                                                                                                                                                                                                  2 of 2 positive at
   c
     Values in parentheses are MICs (in micrograms per milliliter) of the respec-
Blood culture
                                                                                                                                                                                                                                                                                                                                           Positive for 17
                                                                                                                                                                                                                                                                                2 of 2 positive
tive drugs for the isolates from cases 1 and 2 (in that order).
result
Not septic
                                                                                                                                                                                                                                                                                                                                             patients
                                                                                                                                                                                                                                                                                                    3 days
                                                                                                                                                                                                                                                            Positive
                                                                                                                                                                                                                                                            Positive
Positive
                                                                                                                                                                                                                                                                                                  Positive
and discontinued the antibiotic after 2 days of treatment. He
                                                                                                                                                                                                                                                                                                                                                                                   Case 9 was a study of 63 patients (34 female patients and 29 male patients). The age listed is the median age (range, 3 to 97 years).
returned to the clinic 2 weeks later, still complaining of urinary
symptoms, and was febrile at 100.1°F. A second urinalysis
                                                                                                                                                                            Urine culture
Negative
                                                                                                                                                                                                                                                                                                                        Negative
demonstrated 20 to 30 WBCs/HPF, 1 to 3 red blood cells/HPF,
                                                                                                                                                                                                                                                            Normal
                                                                                                                                                                               resultc
                                                                                                                                                                                                         ⬎105
                                                                                                                                                                                                                             5
⬎105
                                                                                                                                                                                                                                                                                ⬎105
                                                                                                                                                                                                                                                                                ⬎105
                                                                                                                                                                                                                                                                                                                                           5
                                                                                                                                                                                                                             ⬎10
                                                                                                                                                                                                                                                                                                                                           ⬎10
a moderate level of leukocyte esterase, and negative urine
chemistries. The urine culture on the second urine sample later
grew ⬎105 CFU of A. urinae, the only isolate, per ml. The
patient was lost to follow-up.
                                                                                                                                                                                                         Nocturia, urinary frequency,
incontinence, pyuria
heart murmur
                                                                                                                                                                                                           incontinence
the present cases and two blood isolates of Aerococcus viridans
                                                                                                                                                                                                           septicemia
from our stock for growth on Trypticase soy agar with 5%
                                                                                                                                                                                                                                                                                                                                                                                   Values given are in CFU per milliliter. The result for case 4 was obtained with a dipstick.
                                                                                                                                                                                                           murmur
                                                                                                                                                                                                           prostate
cerebrovascular disease
indwelling catheter
Prostate cancer
                                                                                                                                                                                                                                                                                                                        Prostate cancer
                                                                                                                                                                                                                                                                                                  Not identified
urinae but is not in the code book. The Vitek gave a unique
                                                                                                                                                                               Sex
                                                                                                                                                                                                                                                            M
                                                                                                                                                                                                                                                            M
                                                                                                                                                                                                                                                                                M
                                                                                                                                                                                                                                                                                M
58
                                                                                                                                                                                                                                                            78
                                                                                                                                                                                                                                                            43
                                                                                                                                                                                                                                                                                81
                                                                                                                                                                                                                                                                                63
81
80
74
1 (PR)
2 (PR)
7 (13)
                                                                                                                                                                                                                                                                                                                                           b
                                                                                                                                                                                                                                                            4 (7)
                                                                                                                                                                                                                                                                                5 (2)
                                                                                                                                                                                                                                                                                6 (2)
8 (8)
9 (4)
omega 9 cis) (12%). However, A. viridans was correctly named          24 h the colony morphology resembles that of an alpha-hemo-
by all these biochemical identification systems. The nucleotide       lytic streptococcus or lactobacillus; at 48 h it is similar to that
sequences of 16S rRNA were determined (MicroSeq 16S                   of an enterococcus. The Gram stain should be differential, as
rRNA gene kit; Perkin-Elmer Applied Biosystems, Foster City,          A. urinae forms pairs, tetrads, and clusters. However, since A.
Calif.). The two isolates were identified as A. urinae by 16S         urinae shows smaller cocci and fewer tetrads than A. viridans
rRNA gene sequencing, with a 0.2 to 0.4% difference from the          does, it could be confused with pediococci or densely packed
type strain. A. urinae demonstrated a 7 to 8% difference from         streptococci or enterococci.
A. viridans, which indicates a genetic diversity similar to that         We characterized our isolates by macroscopic and micro-
found among other well-described genera and does not sup-             scopic appearance, biochemical profiles, CFA analysis, 16S
port Facklam and Elliott’s assertion that these organisms,            rRNA gene sequencing analysis, and antibiotic susceptibilities.
which they call Aerococcus-like organisms, belong in a separate          However, according to our study and previous reports (3, 4,
genus (6).                                                            5, 6), the most important routine tests are detection of leucine
   Antibiotic susceptibility was tested by the disk diffusion         arylamidase, -glucuronidase, PYR, hydrolysis of hippurate
method using Mueller-Hinton blood agar, and the MICs were             (Table 1), and antibiotic susceptibility patterns (Table 2).
determined by E-test. National Committee for Clinical Labo-           Rapid PYR testing is useful for distinguishing between A.
ratory Standards guidelines for Staphylococcus spp. were used         viridans or enterococci (both PYR positive) and A. urinae
for susceptibility testing (11). Our strains of A. urinae are         (PYR negative). A Gram stain should be carefully examined
resistant to trimethoprim-sulfamethoxazole and gentamicin             for the characteristic arrangement in clusters and tetrads to
but susceptible to penicillin (Table 2).                              rule out lactobacillus and other streptococcus. Pediococci are
   Discussion. There are currently three described species of         PYR negative and have a Gram stain morphology similar to
the genus Aerococcus: A. viridans, Aerococcus christensenii, and      that of A. urinae; however, they differ in their resistance to
A. urinae. A. viridans is more commonly isolated from blood           vancomycin and in their positive bile esculin test result. Other
and has been associated with granulocytic bacteremia (9) and          newly described genera that are rarely encountered in the
endocarditis (12). The recently characterized species A. chris-       clinical laboratory can be differentiated by the characteristics
tensenii (5) has not been reported as a human pathogen. A.            listed in Table 1 (6).
urinae, previously known as Aerococcus-like organism, is an
uncommon pathogen. Previous reports from European coun-
tries indicate that it is associated with UTI (4), bacteremia (3),                                      REFERENCES
sepsis (2), and potentially fatal endocarditis (2, 7, 10, 13). The     1. Aguirre, M., and M. D. Collins. 1992. Phylogenetic analysis of some Aero-
main features of our two cases and previously reported cases              coccus-like organisms from urinary tract infections: description of Aerococ-
are summarized in Table 3. One report described a total of 63             cus urinae sp. nov. J. Gen. Microbiol. 138:401–405.
cases of A. urinae infection; however, little clinical information     2. Christensen, J. J., and E. Gutschik. 1991. Urosepticemia and fatal endocar-
                                                                          ditis caused by Aerococcus-like organisms. Scand. J. Infect. Dis. 23:717–721.
was available (4). The single case reports are summarized.             3. Christensen, J. J., I. P. Jensen, and J. Faerk. 1995. Bacteremia/septicemia
Similar to our patients, the other patients are elderly males             due to Aerococcus-like organisms: report of seventeen cases. Clin. Infect.
with a median age of 73 and have underlying predisposing                  Dis. 21:943–947.
conditions, such as prostatic diseases, diabetes mellitus, and         4. Christensen, J. J., H. Vibits, and J. Ursing. 1991. Aerococcus-like organism,
                                                                          a newly recognized potential urinary tract pathogen. J. Clin. Microbiol.
alcoholism. All patients had confirmed UTIs or symptoms typ-              29:1049–1053.
ical of UTI. When these patients were treated with antibiotics         5. Collins, M., M. R. Jovita, and R. A. Huston. 1999. Aerococcus christensenii
effective against A. urinae, as in cases 1, 6, and 8, the infection       sp. nov., from the human vagina. Int. J. Syst. Bacteriol. 49:1125–1128.
resolved and the patients recovered fully. On the other hand,          6. Facklam, R., and J. A. Elliott. 1995. Identification, classification, and clinical
                                                                          relevance of catalase-negative, gram-positive cocci, excluding the strepto-
as in cases 3, 4, 5, and 7, when A. urinae was not recognized or          cocci and enterococci. Clin. Microbiol. Rev. 8:479–495.
correct antibiotic treatment was delayed, simple UTI pro-              7. Gritsch, W., M. Nagl, and J. Hausdorfer. 1999. Septicemia and endomyo-
gressed to systemic infection, including endocarditis and sepsis.         carditis caused by Aerococcus urinae. Wien. Klin. Wochenschr. 11:446–447.
Thus, it is important to consider A. urinae a potential pathogen       8. Hielesen, A. M. 1994. Septicemia due to Aerococcus urinae. Scand. J. Infect.
                                                                          Dis. 26:759–760.
in UTIs especially for patients with predisposing factors who          9. Kern, W., and E. Vanek. 1987. Aerococcus bacteremia associated with gran-
are unresponsive to sulfonamides. If not recognized by the                ulocytopenia. Eur. J. Clin. Microbiol. 6:670–673.
clinician and microbiologist, A. urinae infection can cause se-       10. Kristensen, B., and G. Nielsen. 1995. Endocarditis caused by Aerococcus
rious complications.                                                      urinae, a newly recognized pathogen. Eur. J. Clin. Microbiol. Infect. Dis.
                                                                          14:49–51.
   The laboratory diagnosis of A. urinae can be difficult. The        11. National Committee for Clinical Laboratory Standards. 1998. Performance
presumptive identification of aerobic gram-positive alpha-he-             standards for antimicrobial susceptibility testing; eighth informational sup-
molytic cocci and the decision on whether to more fully iden-             plement. M100-S8. National Committee for Clinical Laboratory Standards,
tify the isolates are frequently based on Gram stain, colony              Wayne, Pa.
                                                                      12. Parker, M. T. 1976. Streptococci and aerococci associated with systemic
appearance, and catalase reaction. Because A. urinae is cata-             infection in man. J. Med. Microbiol. 9:275–302.
lase negative, it could be mistaken for alpha-hemolytic strep-        13. Skov, R. L., M. Klarlund, and S. Thorsen. 1995. Fatal endocarditis due to
tococci or enterococci that are more common urine isolates. At            Aerococcus urinae. Diagn. Microbiol. Infect. Dis. 21:219–221.