American Journal of Epidemiology
Copyright © 2001 by the Johns Hopkins University Bloomberg School of Public Health
All rights reserved
Vol. 154, No. 11
Printed in U.S.A.
Surveillance for Drug-resistant S. pneumoniae Perz et al.
ORIGINAL CONTRIBUTIONS
Evaluation of Innovative Surveillance for Drug-resistant Streptococcus
pneumoniae
Joseph F. Perz,1,2 Allen S. Craig,2,3 Daniel M. Jorgensen,4 Stephanie Hall,4 and William Schaffner2,3
To monitor disease incidence and antibiotic resistance, effective, practical surveillance strategies are needed
at the local level for drug-resistant Streptococcus pneumoniae (DRSP). Knox County, Tennessee, participates in
three forms of DRSP surveillance: an active system sponsored by the Centers for Disease Control and
Prevention (CDC; Atlanta, Georgia); a novel county-sponsored system; and conventional state-mandated
reporting. Ascertainment of invasive S. pneumoniae infection cases by each system in 1998 was evaluated, and
completeness of reporting, antibiotic resistance patterns, costs, and other attributes were compared. The
county-sponsored system collects patient identifiers and drug susceptibility data directly from hospital
laboratories, whereas the CDC-sponsored system performs medical chart abstractions and reference laboratory
susceptibility testing. Similar numbers of invasive S. pneumoniae cases were detected by the county-sponsored
(n = 127) and CDC-sponsored (n = 123) systems; these systems held >75% of all cases in common, and each
system achieved >85% sensitivity. Conventional reporting contained 88% and 76% of the DRSP cases identified
by the county- and CDC-sponsored systems, respectively, but did not capture infections produced by susceptible
isolates. Both the county- and CDC-sponsored systems indicated that large proportions of isolates were
resistant to penicillin and extended-spectrum cephalosporins. The county-sponsored DRSP surveillance system
was inexpensive, simple to execute, and relevant to local needs. Am J Epidemiol 2001;154:1000–5.
community-acquired infections; drug resistance, microbial; epidemiologic methods; laboratories, hospital;
microbial sensitivity tests; pneumococcal infections; population surveillance; Streptococcus pneumoniae
Community-acquired Streptococcus pneumoniae infection remains a major cause of morbidity and mortality (1).
During 1998, S. pneumoniae infection was associated with
approximately 63,000 cases of invasive disease and 6,100
deaths in the United States (2). The difficulties inherent in
managing patients with this infection have been magnified
by the rising incidence of drug-resistant S. pneumoniae
(DRSP) (3–5), which complicates medical care, increases
costs, and impacts patient outcomes (6–10).
Effective, affordable strategies for DRSP surveillance
are needed at the local level to monitor disease incidence
and antibiotic resistance rates and to guide empiric therapy (1). Active, population-based surveillance for invasive pneumococcal disease is sponsored by the Centers
for Disease Control and Prevention (CDC; Atlanta,
Georgia) at a selected number of sites across the United
States as part of the Emerging Infections Program’s
Active Bacterial Core surveillance (ABCs) (2, 3, 11). This
system effectively characterizes antibiotic resistance patterns by testing pneumococcal isolates at reference laboratories and is also used to conduct special studies.
However, because of its costs and complexity, this type of
program is beyond the means of most local and state
health agencies (12).
Knox County, Tennessee (1998 population: 367,000), is
unusual because it is involved in ABCs and also has implemented a simpler, alternative DRSP surveillance system
designed and conducted by the local Knox County Health
Department. In addition, the Tennessee Department of
Health conducts routine passive surveillance for DRSP.
This situation afforded the opportunity to measure the
alternative county-sponsored surveillance strategy against
recognized standards.
Received for publication March 23, 2001, and accepted for publication August 8, 2001.
Abbreviations: ABCs, Active Bacterial Core surveillance; CDC,
Centers for Disease Control and Prevention; DRSP, drug-resistant
Streptococcus pneumoniae; MIC, minimum inhibitory concentration.
1
Epidemic Intelligence Service, Division of Applied Public Health
Training, Epidemiology Program Office, Centers for Disease Control
and Prevention, Atlanta, GA.
2
Communicable and Environmental Disease Services,
Tennessee Department of Health, Nashville, TN.
3
Department of Preventive Medicine, Vanderbilt University
School of Medicine, Nashville, TN.
4
Knox County Health Department, Knoxville, TN.
Reprint requests to Dr. William Schaffner, Department of
Preventive Medicine, Vanderbilt University School of Medicine, A1124 Medical Center North, Nashville, TN 37232-2637 (e-mail:
william.schaffner@mcmail.vanderbilt.edu).
1000
Surveillance for Drug-resistant S. pneumoniae 1001
MATERIALS AND METHODS
DRSP surveillance systems
ABCs. Since 1995, all five Knox County acute care hospitals have participated in the CDC-sponsored ABCs program (2). In 1998, ABCs personnel performed a monthly
review of printed data from the computerized records of
each hospital’s microbiology laboratory to prospectively
identify all cases of invasive S. pneumoniae infection in
Knox County residents (table 1). In cases, S. pneumoniae
was isolated from a normally sterile site. For each case, surveillance personnel also reviewed the medical chart to
abstract clinical and demographic information, and they
requested that clinical isolates from invasive S. pneumoniae
cases be subcultured and forwarded to a reference laboratory (University of Texas Health Sciences Center at San
Antonio) for antibiotic susceptibility testing. Antibiotic susceptibilities were determined by using broth microdilution
(2, 13). Feedback to local medical providers and hospitals
was limited in this system; primarily, system- or state-level
results have been communicated principally through peerreviewed publications and the CDC’s Morbidity and
Mortality Weekly Report.
Knox County Health Department. In 1997, the Knox
County Health Department, in partnership with the surrounding regional health department, initiated a surveillance
program for invasive S. pneumoniae infections with the aim
of generating timely data to monitor resistance trends and
inform medical providers. This surveillance program was
motivated by awareness of high resistance rates among S.
pneumoniae isolates in the region and by a recent outbreak
of drug-resistant pneumococcal meningitis (14). As with
ABCs, all five Knox County hospitals participated in the
Knox County Health Department program in 1998; in addition, three large hospitals serving the region surrounding
Knox County were also included (table 1). Each month, hospital laboratories forwarded a report of all invasive S. pneumoniae isolates to the Knox County Health Department. In
addition to the normally sterile sites used in the ABCs case
definition, the Knox County Health Department system also
included isolates from middle ear, tracheal, and sinus aspirates (not reported here).
The Knox County Health Department system was a
“stimulated” passive system in which health department
personnel solicited reports by telephone if hospitals seemed
to lag in submitting their monthly reports. Reports included
basic demographic data along with the specimen collection
site and date. The results from hospital laboratory antibiotic
susceptibility testing were supplied only when a patient’s
isolate was drug resistant. Except for one hospital that used
broth dilution, susceptibility testing at the hospital laboratories was performed by using antimicrobial gradient strip
tests. No additional patient follow-up or susceptibility testing was conducted. The program used discretionary
resources, absent specific funding. After a Knox County
Health Department medical epidemiologist established the
system, health department personnel requirements were limited generally to the part-time efforts (1 or 2 days per month)
of a communicable disease control nurse and an administrative assistant. Feedback to medical providers took place primarily via local publication of data and related articles in the
Knox County Health Department’s quarterly newsletter.
Conventional reporting. States typically maintain surveillance for a list of notifiable diseases and conditions (15,
16). Laboratories, hospitals, and health-care providers are
required by law to report the occurrence of these conditions
to their local health department. The Tennessee Department
of Health then collects and monitors weekly case reports by
using the National Electronic Telecommunication System
for Surveillance (17); this passive system is referred to here
as “conventional reporting” (table 1). In 1996, Tennessee
adopted the national case reporting criteria for DRSP (clinical cases for whom S. pneumoniae has been isolated from a
normally sterile site that exhibits intermediate- or high-level
resistance to at least one antibiotic approved for treating
pneumococcal infections) (15). DRSP case reports typically
TABLE 1. Attributes of the three surveillance systems used to identify cases of invasive
Streptococcus pneumoniae infections in Knox County, Tennessee, 1998
Attribute
System type
Participating hospitals
Knox County
Regional
Reporting frequency
Chart review
Invasive S. pneumoniae
infections captured
Susceptible isolates
Nonsusceptible isolates
Susceptibility testing
Source
Range of drugs
CDC*-sponsored Active
Bacterial Core
surveillance
Active
Passive, stimulated
Passive
Yes
No
Monthly
Yes
Yes
Yes
Monthly
No
Yes
Yes
Weekly
No
Yes
Yes
Yes
Yes
No
Yes
Reference laboratory
Extensive
Hospital laboratory
Limited
Hospital laboratory
Does not capture testing
data
* CDC, Centers for Disease Control and Prevention.
Am J Epidemiol Vol. 154, No. 11, 2001
Conventional,
state-mandated
reporting
Knox County Health
Department
1002
Perz et al.
originate with hospital infection control practitioners and
include demographic information and the specimen collection date. Antibiotic susceptibility results were not collected,
and no additional patient follow-up or susceptibility testing
was performed. State-level data, summarizing the numbers
of DRSP cases, have been published and distributed to medical providers by the Tennessee Department of Health in its
bimonthly newsletter.
Comparison of the systems’ quantitative attributes
For the present analysis, invasive S. pneumoniae infection
cases were defined as Knox County residents for whom S.
pneumoniae had been isolated from a normally sterile site
(e.g., blood, cerebrospinal fluid, pleural fluid) during 1998.
Residence in Knox County was determined from a review of
patient addresses. Cases meeting this definition were ascertained by reviewing the total set of cases collected by each
system.
Completeness of reporting. Cases with invasive S.
pneumoniae were cross-checked between systems by using
available identifiers such as patient name and address, date
of birth or age, and specimen date. To estimate the number
of additional cases not detected by either ABCs or the Knox
County Health Department, capture-recapture analysis was
applied by using standard methods (18, 19). Completeness
of reporting (i.e., sensitivity) was calculated for the ABCs
and Knox County Health Department systems by dividing
the number of cases in each system by the total number of
cases derived from the capture-recapture analysis. Because
conventional reporting included only invasive cases of S.
pneumoniae deemed drug resistant, comparison with ABCs
and the Knox County Health Department was limited to
DRSP cases.
Antibiotic susceptibility. S. pneumoniae isolates from the
ABCs and Knox County Health Department systems were
categorized (2, 20) as susceptible, having intermediate resistance, or highly resistant to penicillin (susceptible: minimum inhibitory concentration (MIC) ≤ 0.06 µg/ml; intermediate: 0.12 µg/ml ≤ MIC ≤ 1.0 µg/ml; resistant: MIC ≥ 2.0
µg/ml); extended-spectrum cephalosporins (ceftriaxone
disodium or cefotaxime sodium) (susceptible: MIC ≤ 0.5
µg/ml; intermediate: MIC 1.0 µg/ml; resistant: MIC ≥ 2.0
µg/ml); erythromycin (susceptible: MIC ≤ 0.25 µg/ml; intermediate: MIC 0.5 µg/ml; resistant: MIC ≥ 1.0 µg/ml);
chloramphenicol (susceptible: MIC ≤ 4.0 µg; resistant: MIC
≥ 8.0 µg/ml); and clindamycin (susceptible: MIC ≤ 0.25
µg/ml; intermediate: MIC 0.5 µg/ml; resistant: MIC ≥ 1.0
µg/ml). An isolate was defined as “resistant” to a particular
antibiotic if it exhibited either intermediate- or high-level
resistance to that agent. The sources of antibiotic susceptibility data were the CDC reference laboratory for ABCs
cases and the hospital laboratories for Knox County Health
Department cases. MIC values based on gradient strip testing that fell between standard twofold dilutions were
rounded upward to the next standard dilution before categorization, per the manufacturer’s instructions (AB Biodisk,
Piscataway, New Jersey). Differences between the ABCs
and Knox County Health Department systems in the pro-
portions of isolates within particular antibiotic susceptibility
categories were evaluated with the Fisher’s exact test by
using Stata statistical software, release 6.0 (Stata
Corporation, College Station, Texas).
Timeliness and costs. Timeliness was assessed by comparing the median time between specimen collection with
the completion of reference laboratory testing (for ABCs) or
reporting to the health department (for Knox County Health
Department and conventional reporting). Direct and indirect
costs were estimated for 1998 on the basis of interviews
with relevant personnel from the different surveillance systems. The level of effort associated with conventional
reporting was designated as a baseline to which no costs
were ascribed. For ABCs, the costs for this surveillance
were determined by estimating the additional staff time
required by hospital laboratories (e.g., for subculturing), the
ABCs program’s personnel and administrative requirements, and the additional costs of testing by the reference
laboratory. Interpretation and analysis by CDC personnel
were not included. For the Knox County Health
Department, costs were based on the estimated staff time
required by the hospital laboratories to assemble and transmit monthly reports and by local health department staff to
enter and disseminate these data.
RESULTS
Completeness of reporting
During 1998, the ABCs and Knox County Health
Department systems detected 123 and 127 cases, respectively, of invasive S. pneumoniae infections in Knox County
residents (table 2). When the results of both systems were
combined, the total number of individual cases was 141; of
these, 109 (77 percent) were found to be common to both
systems. The remaining cases were found in only one system: 14 cases were unique to ABCs and 18 cases were
unique to the Knox County Health Department. Eight (44
percent) of the 18 unique Knox County Health Department
cases originated from a hospital geographically outside of
Knox County and were not included in the ABCs system.
Among the five Knox County hospitals, each surveillance
system typically captured at least one case missed by the
other, but no consistent hospital-specific pattern was evident. Two additional cases were predicted by the capture-
TABLE 2. Completeness of reporting comparing the
numbers of cases of invasive Streptococcus pneumoniae
infections detected in the ABCs* and KCHD* systems,
Knox County, Tennessee, 1998
ABCs
(n = 123)
Yes
No
KCHD
(n = 127)
Yes
No
109
18
14
* ABCs, Active Bacterial Core surveillance; KCHD, Knox County
Health Department.
Am J Epidemiol Vol. 154, No. 11, 2001
Surveillance for Drug-resistant S. pneumoniae 1003
recapture analysis; the estimated total number of cases was
143. The overall completeness of the ABCs and Knox
County Health Department systems was then calculated as
86 and 89 percent, respectively.
Comparison to conventional reporting
A total of 52 cases of invasive DRSP infection occurring
in Knox County residents in 1998 were reported to the
Tennessee Department of Health (figure 1). Cases of invasive S. pneumoniae were reportable to the state only if the
isolates were drug resistant, so infections produced by susceptible isolates were not captured. All 52 of the DRSP
FIGURE 1. Number of cases of invasive Streptococcus pneumoniae, by surveillance system and reported penicillin susceptibility category, Knox County, Tennessee, 1998. ABCs, Active Bacterial Core
surveillance; KCHD, Knox County Health Department.
cases captured by conventional reporting were also identified by either the ABCs or Knox County Health Department
system; 48 cases were common to all three systems. The
conventional reporting system contained 88 percent (50/57)
of the reported invasive DRSP infections documented in the
Knox County Health Department system. When only the
ABCs cases available for testing at the reference laboratory
were considered, conventional reporting captured 76 percent (41/54) of the ones determined to be drug resistant.
Antibiotic susceptibility
Isolates of invasive S. pneumoniae were classified as susceptible or resistant according to the results of the antibiotic
susceptibility testing for the ABCs cases whose isolates
were tested by the reference laboratory (n 98) and for all
Knox County Health Department cases (n 127) (figure 1).
(The resistant category was comprised of isolates exhibiting
either intermediate- or high-level resistance.) Both the
ABCs and Knox County Health Department systems indicated that large proportions of isolates were resistant to
penicillin and extended-spectrum cephalosporins (table 3).
The proportion of isolates characterized as penicillin
resistant was higher among isolates reported by ABCs than
by the Knox County Health Department (55 vs. 45 percent),
but this difference was not statistically significant. ABCs
testing detected a greater proportion of isolates with highlevel penicillin resistance (44 vs. 27 percent, p 0.01).
For extended-spectrum cephalosporins, ABCs found
greater proportions of isolates that were resistant (44 vs. 25
percent, p 0.004) or had high-level resistance (30 vs. 13
percent, p 0.002). The proportion of isolates resistant to
erythromycin was substantial in both systems, although
nominally higher with ABCs (37 vs. 26 percent, p 0.10).
For both clindamycin and chloramphenicol, similarly high
TABLE 3. Antibiotic susceptibilities of invasive Streptococcus pneumoniae isolates from the ABCs*
and KCHD* systems, Knox County, Tennessee, 1998
Proportion of isolates (%)
Susceptibility
category†
Antibiotic
Penicillin
Extended-spectrum
cephalosporins
Erythromycin
Clindamycin
Chloramphenicol
p value
ABCs‡
KCHD§
Difference (95% CI*)
Resistant
Intermediate
High level
55
11
44
45
18
27
10 (–3, 23)
–7 (–16, 2)
17 (5, 30)
NS¶
NS
0.01
Resistant
Intermediate
High level
Resistant
Resistant
Resistant
44
14
30
37
2
2
25
13
13
26
3
1
19 (6, 31)
2 (–7, 11)
17 (6, 28)
11 (–2, 23)
–1 (–6, 3)
1 (–3, 5)
0.004
NS
0.002
NS
NS
NS
* ABCs, Active Bacterial Core surveillance; KCHD, Knox County Health Department; CI, confidence interval.
† Refer to the Materials and Methods section of the text for susceptibility definitions via minimum inhibitory
concentration.
‡ Based on 98 isolates tested by the ABCs reference laboratory.
§ Based on isolates tested by hospital laboratories (penicillin and extended-spectrum cephalosporins, n = 127;
erythromycin and clindamycin, n = 116; and chloramphenicol, n = 93).
¶ NS, nonsignificant at the a2 = 0.05 level.
Am J Epidemiol Vol. 154, No. 11, 2001
1004
Perz et al.
proportions (>96 percent) of isolates were susceptible
according to both reporting systems.
Timeliness and costs
The average time to complete reporting was approximately 4 months for ABCs compared with 1 month for the
Knox County Health Department and 3 weeks for conventional reporting. The annual cost of the ABCs system was an
estimated $30,000, including $25,000 for surveillance personnel and administrative costs, $2,000 for hospital personnel requirements, and $3,000 for reference laboratory testing.
In contrast, on the basis of hospital and health department
personnel requirements, the Knox County Health
Department system cost approximately $5,000 annually.
DISCUSSION
In Knox County, Tennessee, it was possible to compare
the usefulness of three concurrent surveillance systems for
invasive infections produced by antibiotic-resistant S. pneumoniae: a traditional, passive, state-mandated reporting
mechanism; a simple, innovative, county-sponsored system
established in response to local needs (Knox County Health
Department); and a CDC-sponsored, active, populationbased system (ABCs) that served as a relative “gold standard.” The simple local reporting system devised by the
Knox County Health Department performed well.
All three surveillance systems successfully recorded a
comparable occurrence of penicillin-resistant pneumococcal
isolates from usually sterile sites. Somewhat surprisingly,
the Knox County Health Department system recorded more
total cases of invasive S. pneumoniae infection among Knox
County residents in 1998 than the ABCs system did. This
occurrence was largely explained by the Knox County
Health Department system including a hospital in one of the
counties bordering Knox County, which was not part of the
ABCs network. Geographically delineated surveillance systems will always have the potential to miss patients who
seek care outside the catchment area.
As anticipated, the traditional, passive, state-sponsored
reporting system recorded the smallest number of cases, but
the difference was not large. Thus, conventional reporting
appeared to provide an effective means of gauging the incidence of invasive DRSP infection. However, conventional
reporting had a notable drawback. Because only DRSP was
reportable, the proportion of isolates susceptible to penicillin could not be determined. Tennessee now requires that
antibiotic-susceptible invasive pneumococcal infections
also be reported, which makes the data more useful in
determining the proportion of resistant isolates.
Differences were observed between the Knox County
Health Department and ABCs systems in the proportions of
isolates classified among some antibiotic susceptibility categories. Restricting the analysis to only those isolates tested
by both the hospitals and reference laboratory did not affect
these results (data not shown). These differences are unlikely
to have an impact on the usefulness of either system as a public health tool. However, a potential clinical impact existed in
those instances when the hospital laboratory reported an iso-
late as susceptible to penicillin and the ABCs reference laboratory determined that it was resistant; these types of differences are now under investigation. Similarly, interlaboratory
differences in extended-spectrum cephalosporin susceptibility results have been noted previously (21).
The principal motivation for establishing these surveillance
systems was the emergence of antibiotic-resistant S. pneumoniae. Few areas have successfully implemented DRSP surveillance, despite the fact that practical data exist in most
community hospitals (22, 23). Resources available for local
surveillance are scarce. For DRSP, formulating the appropriate scope of a local surveillance system presents an additional
difficulty. The ABCs system does not provide a suitable
model because its considerable scope and resource requirements, which reflect its research-oriented role and national
perspective, exceed local needs and capacities. The Knox
County Health Department system was innovative in that it
established a collaborative mechanism with local hospitals to
assemble, monitor, and disseminate community-level DRSP
data to providers in an efficient and timely manner.
Many hospitals compile antibiograms from the results of
their own susceptibility testing. Typically, they do not distinguish between invasive and noninvasive infections, multiple isolates from individual patients, or intermediate and
resistant interpretive categories. A surveillance strategy that
provided community-level DRSP data from the aggregation
of local hospital antibiograms has been described (12, 24).
Similar to the Knox County Health Department system, this
alternate strategy also provides a sufficient body of continuous data to enable examination of trends and is useful in
both the local public health and clinical arenas. However,
the Knox County Health Department system provides a
finer level of detail because it accesses the specific microbiologic and demographic data from individual patient isolates. Thus, this system preserves distinctions regarding
susceptibility categories, patient demographics, and invasive versus noninvasive infections. In addition, because not
all hospitals produce antibiograms, the Knox County Health
Department approach might make these data more representative and accessible. Another recent example of alternative
DRSP surveillance involved a sample of hospitals from
Washington State (2, 25); this system collected periodic
reports containing patient-level data on invasive S. pneumoniae infections, and it seemed to provide adequate, detailed
monitoring of DRSP at the state level.
A heightened level of awareness exists in the Knox
County community regarding the public health importance
of pneumococcal drug resistance, and this awareness may
have enhanced cooperation on the part of the hospital laboratories. It was not possible to evaluate the effect that prior
participation in the ABCs program may have had on reporting through the separate Knox County Health Department
mechanism. The existence of multiple, overlapping reporting systems in a given locale does raise some concerns,
especially for the laboratory, medical, and public health professionals whose responsibility it is to actually perform disease reporting. Integration of disease surveillance systems
has become a major focus in recent years, and the proposed
CDC National Electronic Disease Surveillance System aims
Am J Epidemiol Vol. 154, No. 11, 2001
Surveillance for Drug-resistant S. pneumoniae 1005
to provide an Internet-based communications infrastructure
that will streamline disease reporting at the local, state, and
national levels (26). Specifically, implementation of electronic data transmission from clinical laboratories should
reduce the burden of disease reporting and may also facilitate collection of the detailed susceptibility data needed for
enhanced DRSP surveillance.
In summary, the Knox County Health Department surveillance system for DRSP infections was accurate, timely,
and simple to execute. This system did not require dedicated
funding or the hiring of additional personnel. This surveillance system has been used to supply timely data to medical
providers to define the magnitude and nature of the problem
of drug resistance, inform empiric therapies, and monitor
changes. Resource outlays have been balanced with a scope
appropriate and relevant to local needs. The Knox County
Health Department system could serve as a model for other
communities concerned about the emergence of DRSP.
9.
10.
11.
12.
13.
14.
15.
ACKNOWLEDGMENTS
The authors are grateful to Dr. Laura Fehrs, Dr. Ron
Moolenaar, Dr. Cynthia Whitney, Dr. Anne Schuchat, Dr.
Paul Erwin, Brenda Barnes, Jan Fowler, Sandra Blakely, and
personnel from the participating hospitals and laboratories
for their helpful comments and contributions to this project.
16.
17.
18.
19.
20.
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