Invasive group B streptococcal disease in the elderly, Minnesota, USA, 2003-2007.
Article Type: Report
Subject: Comorbidity (Research)
Comorbidity (Causes of)
Aged (Health aspects)
Streptococcal infections (Risk factors)
Streptococcal infections (Distribution)
Streptococcal infections (Drug therapy)
Streptococcal infections (Research)
Authors: Kothari, Neelay J.
Morin, Craig A.
Glennen, Anita
Jackson, Delois
Harper, Jane
Schrag, Stephanie J.
Lynfield, Ruth
Pub Date: 08/01/2009
Publication: Name: Emerging Infectious Diseases Publisher: U.S. National Center for Infectious Diseases Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 U.S. National Center for Infectious Diseases ISSN: 1080-6040
Issue: Date: August, 2009 Source Volume: 15 Source Issue: 8
Topic: Event Code: 310 Science & research; 690 Goods & services distribution Advertising Code: 59 Channels of Distribution Computer Subject: Company distribution practices
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 215924958
Full Text: Invasive group B streptococcal (GBS) disease is a major cause of illness and death in older adults (1). A 2- to 4-fold increase in invasive GBS disease among US adults has been reported since the 1980s (2), and incidence increased 32% in adults from 1999 through 2005 (1). The objective of this study was to characterize the incidence and epidemiology of GBS disease in Minnesota among the elderly in long-term care facilities (LTCFs) and in the community.

The Study

The Minnesota Department of Health conducts statewide, population-based surveillance for GBS disease as part of the Centers for Disease Control and Prevention Active Bacterial Core Surveillance Network/Emerging Infections Program. Invasive disease is defined as isolation of GBS bacteria from a normally sterile site, such as blood, pleural fluid, cerebrospinal fluid, joint fluid, or bone (3). To ensure completeness of reporting, the Minnesota Department of Health audits laboratories to identify all GBS bacteria-positive cultures from normally sterile sites. For each case, a standardized case report form is completed by hospital infection control practitioners. GBS isolates are sent to the Minnesota Department of Health Public Health Laboratory for susceptibility testing using broth microdilution. Erythromycin-resistant, clindamycin-susceptible isolates are tested for inducible clindamycin resistance by double-disk diffusion (D test). Interpretation is based on Clinical and Laboratory and Standard Institute protocols (4). Serotyping is performed at the Centers for Disease Control and Prevention by latex agglutination tests with rabbit antiserum to GBS capsular polysaccharide types Ia, Ib, and II-VIII (5). When latex tests are indeterminate, the Lancefield method is used (6).

The study comprised all Minnesota residents aged >65 years with invasive GBS disease during 2003-2007. LTCF residence was defined as living in an LTCF before the date of first positive culture. Resident addresses were checked by a reverse-address directory to determine whether they corresponded with the address of an LTCF. All other residents were defined as community dwelling. Incidence was calculated using 2000 census data. Analyses were conducted using SAS version 9.1 (SAS Institute, Cary, NC, USA); the [chi square] test was used to evaluate differences in proportions for discrete variables.

A total of 723 cases of invasive GBS disease among persons [greater than or equal to] 65 years of age were reported; 596 (82.4%) cases occurred among community residents, and 127 (17.6%) occurred among LTCF residents (Table 1). The overall incidence rate was 24.3 cases per 100,000 persons. Incidence did not vary significantly by year but did increase with age (19.3/100,000 at 65-74 years, 26.3/100,000 at 75-84 years, and 36.9/100,000 at [greater than or equal to] 85 years; [chi square] for trend = 44.4, p<0.001) and was higher among LTCF residents than among community residents (67.7/100,000 vs. 21.4/100,000; p<0.001). The overall case-fatality rate was 6.8 (8.7% LTCF vs. 6.4% community). Case-fatality rates increased as age increased (6.0% at 65-74 years, 6.8% at 75-84 years, and 8.2% at [greater than or equal to] 85 years).

The most common clinical presentation reported was bacteremia without focus (50.2%), followed by pneumonia (10.9%). LTCF residents (18.9%) were more likely than community residents (9.2%) to have pneumonia (p = 0.002) (Table 1). Blood (84.0%) was the most common site for isolation of GBS bacteria, followed by joint fluid (10.2%) and bone (3.3%). Other sites included peritoneal fluid (1.4%), pleural fluid (0.7%), and cerebrospinal fluid (0.4%).

Data on concurrent conditions were collected for 96 (75.6%) of 127 LTCF case-patients and 448 (75.2%) of 596 community case-patients. Of these, 176 (32.3%) had only 1 concurrent condition, 166 (30.5%) had 2 concurrent conditions, and 145 (26.6%) had [greater than or equal to] 3 concurrent conditions. LTCF residents (94.8%) were more likely than community residents (88.4%) to have a documented concurrent condition (p = 0.06) (Table 1). Among case-patients with known concurrent condition status, 41% had diabetes mellitus and 30% had coronary artery disease; similar proportions were noted among LTCF and community case-patients. Congestive heart failure (26.0% vs. 15.0%, p = 0.009), stroke (13.5% vs. 5.1%, p = 0.003), and chronic obstructive pulmonary disease (15.6% vs. 8.3%, p = 0.026) were more common among LTCF residents. Cancer was more common among community residents (28.1% vs. 13.5%, p = 0.003) (Table 1). Cellulitis as a manifestation of invasive GBS disease was more likely in residents with diabetes than in those without diabetes (24.4% vs. 16.3%, p = 0.019).

GBS serotypes were obtained for 654 (90.5%) of 723 case-patients. Five serotypes, Ia (21.1%), Ib (11.0%) II (11.8%), III (11.3%), and V (35.0%), accounted for 94.6% of LTCF case-patients and 89.7% of community case-patients. Antimicrobial drug susceptibility data were obtained for 655 (90.6%) of 723 case-patients. All isolates were susceptible to penicillin. Susceptibility to erythromycin and clindamycin decreased during 2003-2007 (Table 2). Sixty percent of erythromycin-resistant, clindamycin-susceptible isolates had inducible clindamycin resistance as evidenced by a positive D test. During 2004-2005, 78% of erythromycin-resistant, clindamycin-susceptible isolates had inducible clindamycin resistance compared with 46% from 2006-2007 (p = 0.003). Serotype V was associated with higher rates of resistance than other serotypes to both erythromycin (46.7% vs. 27.9%, p<0.001) and clindamycin (28.4% vs. 12.9%, p<0.001). Serotype V was also associated with higher rates of inducible clindamycin resistance (88.6% vs. 43.4%, p<0.001).

Conclusions

We found that rates of invasive GBS disease were substantial among the elderly and 3x higher among LTCF residents than elderly persons living in the community. These results are supported by an earlier report from Maryland that also found increased incidence of invasive GBS infections in LTCF residents (7). The reason for increased incidence in LTCF residents is not fully known. However, concurrent conditions, such as advanced age, diabetes, cirrhosis, and stroke, are known risk factors for GBS infection (8). In our study, concurrent conditions were common among both groups, however, concurrent condition types differed by group. Although higher rates of GBS disease among LTCF residents may be caused in part by differences in underlying concurrent conditions, other factors not collected as part of this study may also play a role. These factors include use of invasive devices (urinary catheters, intravenous catheters) and the possible role of person-to-person transmission of GBS bacteria in LTCF settings.

Case-fatality rates in this study were lower than those reported in other studies. National surveillance data (1) have shown a case-fatality rate of 13.1% for persons [greater than or equal to] 65 years of age, and a similar study among LTCF residents showed a case-fatality rate of 16.7% (7).

Macrolide resistance is common, and increases in clindamycin resistance continue to occur among GBS strains. In the era of methicillin-resistant Staphylococcus aureus infections, nonpenicillin agents, such as clindamycin, are increasingly being used for empiric treatment of skin and soft tissue infections, but they may not provide adequate coverage if these infections are caused by GBS bacteria. Although [beta]-lactams remain the preferred therapy for GBS infections, strains with elevated penicillin MICs have recently been reported (9-11).

The prevalence of serogroup V in this study is consistent with findings from other studies of adult populations (12,13) that show the recent emergence of this serotype. Serotype V has been associated with higher rates of antimicrobial drug resistance (14); thus, following trends in serotype prevalence may be useful. High rates of antimicrobial drug use in the elderly may result in further selection of serotype V, and resistance may increase in other serotypes. Molecular studies may be useful to further evaluate strains because serologically nontypeable strains contained specific capsular polysaccharide genes, including those for V (15). LTCF residents and persons with concurrent conditions should have high priority for vaccine administration after a vaccine becomes available. Vaccines should be multivalent; based on predominant serotypes, currently Ia, Ib, II, III, and V; and effective and immunogenic for older adults.

References

(1.) Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. 2008;299:2056-65. DOI: 10.1001/jama.299.17.2056

(2.) Farley MM. Group B streptococcal disease in nonpregnant adults. Clin Infect Dis. 2001;33:556-61. DOI: 10.1086/322696

(3.) Zangwill KM, Schuchat A, Wenger JD. Group B streptococcal disease in the United States, 1990: report from a multistate active surveillance system. MMWR CDC Surveill Summ. 1992;41:25-32.

(4.) Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 15th informational supplement. CLSI/NCCLS document M100-S15. Wayne (PA); The Institute; 2005.

(5.) Slotved HC, Elliot J, Thompson T, Kondrason HB. Latex assay for serotyping of group B streptococcus isolates. J Clin Microbiol. 2003;41:4445-7. DOI: 10.1128/JCM.41.9.4445-4447.2003

(6.) Heard SR, Mawn JA. New phenotypic typing scheme for group B streptococci. J Clin Pathol. 1993;46:145-8. DOI: 10.1136/ jcp.46.2.145

(7.) Henning KJ, Hall EL, Dwyer DM, Billmann L, Schuchat A, Johnson JA, et al. Invasive group B streptococcal disease in Maryland nursing home residents. J Infect Dis. 2001;183:1138-42. DOI: 10.1086/319278

(8.) Farley MM, Harvey RC, Stull T, Smith JD, Schuchat A, Wenger JD, et al. A population-based assessment of invasive disease due to group B streptococcus in nonpregnant adults. N Engl J Med. 1993;328:1807-11. DOI: 10.1056/NEJM199306243282503

(9.) Kimura K, Suzuki S, Wachino J, Kurokawa H, Yamane K, Shibata N, et al. First molecular characterization of group B streptococci with reduced penicillin susceptibility. Antimicrob Agents Chemother. 2008;52:2890-7. DOI: 10.1128/AAC.00185-08

(10.) Dahesh S, Hensler ME, Van Sorge NM, Gertz RE Jr, Schrag S, Nizet V, et al. Point mutation in the group B streptococcus pbp2x gene conferring decreased susceptibility to beta-lactam antibiotics. Antimicrob Agents Chemother. 2008;52:2915-8. DOI: 10.1128/ AAC.00461-08

(11.) Nagano N, Nagano Y, Kimura K, Tamai K, Yanagisawa H, Arakawa Y. Genetic heterogeneity in pbp genes among clinically isolated group B streptococci with reduced penicillin susceptibility. Antimicrob Agents Chemother. 2008;52:4258-67. DOI: 10.1128/ AAC.00596-08

(12.) Blumberg HM, Stephens DS, Modansky M, Erwin M, Elliot J, Facklam RR, et al. Invasive group B streptococcal disease: the emergence of serotype V. J Infect Dis. 1996;163:365-73.

(13.) Skoff T, Farley MM, Moehle-Boetani J, Gershman K, Barrett NL, Harrison L., et al. The epidemiology of invasive group B streptococcal disease in non-pregnant adults. Presented at: International Conference on Emerging Infectious Diseases; March 19-22, 2006; Atlanta, GA, USA. Abstract No. 153 [cited 2009 May 10]. Available from http://www.iceid.org/documents/AbstractsFinal.pdf

(14.) Andrews JI, Diekema DJ, Hunter SK, Rhomberg PR, Pfaller MA, Jones RN, et al. Group B streptococci causing neonatal bloodstream infection: antimicrobial susceptibility and serotyping results from SENTRY centers in the Western Hemisphere. Am J Obstet Gynecol. 2000;183:859-62. DOI: 10.1067/mob.2000.108839

(15.) Ramaswamy SV, Ferrieri P, Flores AE, Paoletti LC. Molecular characterization of nontypeable group B streptococcus. J Clin Microbiol. 2006;44:2398-403. DOI: 10.1128/JCM.02236-05

Author affiliations: Minnesota Department of Health, St. Paul, Minnesota, USA (N.J. Kothari, C.A. Morin, A. Glennen, J. Harper, R. Lynfield); University of Minnesota, Minneapolis, Minnesota, USA (N.J. Kothari); and Centers for Disease Control and Prevention, Atlanta, Georgia, USA (D. Jackson, S.J. Schrag)

DOI: 10.3201/eid1508.081381

Address for correspondence: Neelay J. Kothari, 625 Robert St North, PO Box 64975, St. Paul, MN 55164-0975, USA; email: koth0036@umn.edu

Dr Kothari recently completed an Infectious Diseases Fellowship at the University of Minnesota. His research interests include the epidemiology of infections among residents of longterm care facilities, with a focus on antimicrobial drug resistance and appropriate use of antimicrobial drugs in this population.
Table 1. Comparison of LTCF residents and community-dwelling elderly
persons with invasive GBS disease, Minnesota, 2003-2007 *

                                                          Community
                                       LTCF elderly,       elderly,
Characteristic                            no. (%)          no. (%)

Total no. case-patients                     127              596
Male gender                              63 (49.6)        338 (56.7)

Type of infection ([dagger])             63 (49.6)        297 (49.8)
  Bacteremia without focus               24 (18.9)         55 (9.2)
  Pneumonia                              17 (13.4)        120 (20.1)
  Cellulitis                              5 (3.9)          47 (7.9)
  Septic arthritis                        5 (3.9)          24 (4.0)
  Osteomyelitis                           6 (4.7)          20 (3.4)
  Abscess                                 1 (0.8)          3 (0.5)
  Meningitis                             13 (11.0)        58 (10.2)
  Other or >2 types                       7 (5.5)          27 (4.5)

Concurrent condition data collected      96 (75.6)        448 (75.2)
  No concurrent conditions                5 (5.2)         52 (11.6)
  1 concurrent condition                 34 (35.4)        142 (31.7)
  2 concurrent conditions                34 (35.4)        132 (29.5)
  [greater than or equal to] 3           23 (24.0)        122 (27.2)
    concurrent conditions

Concurrent condition types               39 (40.6)        186 (41.5)
    ([double dagger])
  Diabetes                               26 (27.1)        135 (30.1)
  ASCVD                                  25 (26.0)        67 (15.0)
  Congestive heart failure               13 (13.5)         23 (5.1)
  Stroke                                 15 (15.6)         37 (8.3)
  COPD                                   13 (13.5)        126 (28.1)
  Cancer                                 44 (45.8)        195 (43.5)

Died                                      11 (8.7)         38 (6.4)

* LTCF residents were a median of 84 years of age; community
residents, a median of 76 years of age (p<0.05). LTCF, long-term
care facility; GBS, group B streptococcal; ASCVD, atherosclerotic
cardiovascular disease; COPD, chronic obstructive pulmonary disease.

([dagger]) A single patient may have had >1 type of infection.

([double dagger]) Percentages are of those with concurrent condition
data collected.

Table 2. Susceptibility of invasive GBS disease to erythromycin and
clindamycin, Minnesota, 2003-2007 *

                                      No. (%) case-patients

                               2003           2004           2005
Susceptibility              (N = 133)      (N = 127)      (N = 131)

Erythromycin susceptible    95 (71.4)      86 (67.7)      87 (66.4)
Clindamycin susceptible     114 (85.7)     105 (82.7)     108 (82.4)

                              No. (%) case-patients

                               2006           2007         p value
Susceptibility              (N = 143)      (N = 121)      ([dagger])

Erythromycin susceptible    90 (62.9)      71 (58.7)        0.023
Clindamycin susceptible     116 (81.1)     92 (76.0)        0.057

* GBS, group B streptococcal.

([dagger]) [x.sup.2] test for trend.
Gale Copyright: Copyright 2009 Gale, Cengage Learning. All rights reserved.