Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. During the past decade, the prevalence of penicillin resistance in S pneumoniae has increased dramatically, with resistance rates approaching 45% in some areas of the United States. Streptococcus pneumoniae has also acquired resistance to other commonly used antimicrobials, including cephalosporins, macrolides, and trimethoprim-sulfamethoxazole. While vancomycin and the newer quinolones are currently highly active against most strains of S pneumoniae, reduced susceptibilities to these agents have been identified in some strains. Prior use of antimicrobial agents is the major risk factor for colonization and infection with antibiotic-resistant strains. p-Lactam antibiotics remain the treatment of choice for infections caused by susceptible S pneumoniae. The optimum therapy for penicillin-resistant strains remains unclear. Appropriate empirical therapy for patients with community-acquired pneumonia depends in part on the community-specific resistance patterns of S pneumoniae to various antibiotics. In this article, we provide an overview of the development of S pneumoniae resistance to commonly used antibiotics and discuss the implications of the development of resistance on treatment decisions.
Community-acquired pneumonia (CAP) leads to considerable morbidity and mortality. Medical expenditures attributable to CAP amount to almost $10 billion annually in the United States, with inpatient costs accounting for more than 90% of total costs.
1
Streptococcus pneumoniae (pneumococcus) is the leading identified pathogen in patients with CAP.2
3
Even in those patients with CAP in whom an organism is not identified by routine diagnostic testing, S pneumoniae is likely to be the causative agent.' Streptococcus pneumoniae is implicated in nearly 500,000 cases of CAP annually in the United States,3
with annual expenditures for the treatment of pneumococcal infections exceeding $4 billion.5
Case-fatality rates for bacteremia or pneumonia caused by S pneumoniae are also substantial, ranging from 9% to 30%.3
6
, 7
, 8
For more than 4 decades, penicillin G was the mainstay of therapy for pneumococcal infection. However, the prevalence of penicillin-resistant pneumococci, first reported in the 1960s, has escalated at an alarming rate within the past decade.9
, 10
, 11
, 12
By 1997, about one third of pneumococci were resistant to penicillin.” Unfortunately, penicillin-resistant strains are also often resistant to non—β-lactam antibiotics, including macrolides, clindamycin, tetracyclines, chloramphenicol, and trimethoprim-sulfamethoxazole (TMP-SMX).9
10
12
Development of antimicrobial resistance to specific classes of antimicrobials reflects patterns of antibiotic use.5
8
13
14
The vast majority of S pneumoniae strains (both penicillin-sensitive and penicillin-resistant) are susceptible to carbapenems, rifarnpin, and the newer fluoroquinolones.
5
, 10
, 15
, 16
, 17
, 18
More than 90% of strains are susceptible to carbapenems.12
Although the newer fluoroquinolones also have activity against more than 99% of isolates, reports of decreased susceptibility of pneumococci to fluoroquinolones are emerging.19
All strains of pneumococci remain susceptible to vancomycin; however, the development of tolerance to vancomycin in some strains of S pneumoniae suggests vancomycin resistance may soon emerge.3
5
10
12
20
21
When treatment decisions must be made for an individual patient with CAP, the physician is usually unaware of the exact pathogen causing the infection and, thus, is unaware also of the precise antimicrobial susceptibilities. 2,4,22,23 Therefore, most treatment of CAP is given on an empirical basis, often based on clinical practice guide lines.
23
, 24
, 25
When choosing an antibiotic for the treatment of CAP, physicians must be aware of the current patterns of antibiotic susceptibility in their community, as well as the patient's risk factors for carriage of resistant pneumococci.- Niederman MS
- Bass Jr, JB
- Campbell GD
- et al.
American Thoracic Society, Medical Section of the American Lung Association. Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy.
Am Rev Respir Dis. 1993; 148: 1418-1426
PENICILLIN RESISTANCE TO S PNEUMONIAE
Pneumococcal susceptibilities to penicillin are defined in terms of the minimum inhibitory concentration (MIC) of penicillin. Streptococcus pneumoniae is susceptible to penicillin if the MIC is 0.06 ug/ml, or lower, has intermediate resistance if the MIC is 0.1 to 1.0 ug/ml., and is resistant if the MIC is 2 ug/ml, or higher.
9
11
26
Penicillin resistance is caused by mutations in chromosomal genes, which lead to alterations in penicillin-binding proteins (PBPS).9
, 10
, 11
, 27
Alteration of PBPs decreases binding to penicillin and other β-lactam antibiotics, including β-lactamase inhibitor combinations and cephalosporins.5
15
27
Resistance has occurred primarily through a stepwise process, with successive genetic mutations resulting in increasing resistance.
27
28
In addition, some evidence suggests that S pneumoniae gained penicillin resistance genes through transformation with penicillin-resistant viridans streptococci.27
28
Finally, clonal dissemination of resistant strains of pneumococci has occurred in the United States and worldwide. Currently in the United States, most strains of penicillin-resistant S pneumoniae are represented by relatively few clonal groups.29
This suggests that the US strains arose from a few imported strains of penicillin-resistant pneumococci circulating in other countries.29
Rates of resistance to non—β-lactam antimicrobials are also higher in penicillin-resistant strains.
5
10
27
30
Resistance to non—β-lactam antibiotics may be acquired through transformation of DNA from other streptococcus species (eg, viridans group streptococci), transposons, or diverse spontaneous mutations due to selection pressure.5
, 10
, 12
, 27
, 30
Antimicrobial resistance correlates with specific serotypes in the pneumococci. More than 80% of resistant isolates are classified into 6 serotypes (6A, 6B, 9V, 14, 19F, 23F).
9
11
12
15
31
All these serotypes are associated with infections in humans and are represented by the currently available pneumococcal vaccine. Serotypes1
, 3
, 4
, 5
, 7
, 11
, 15
and 18 rarely carry antibiotic-resistant genes.9
, 10
, 11
, 12
15
32
Prevalence and Epidemiology
The prevalence of penicillin resistance among
The prevalence of penicillin resistance among pneumococci varies widely. Penicillin-resistant pneumococci arose from a few clones in a few geographic locations (eg, South Africa, Australia) in the late 1960s and then spread throughout the world.
10
12
15
27
32
However, multiple genetic mutations that confer resistance have emerged independently in Switzerland and other selected countries.15
The rate of penicillin resistance is very high in some areas (eg, Spain, Israel, South Africa), ranging from 25% to 86%.3
8
14
In contrast, penicillin-resistant strains remain uncommon (<5%) in Sweden, Finland, Canada, and some other geographic areas.15
, 27
, 28
, 29
, 30
, 31
, 32
, 33
In the United States, the prevalence of penicillin resistance is highly variable.5
10
12
15
34
In 1997, a survey by the Centers for Disease Control and Prevention (CDC) found that 25% of 3237 isolates from patients with invasive pneumococcal disease were not susceptible to penicillin.34
However, the proportion varied widely between geographic areas; Maryland had the lowest rate of strains not susceptible to penicillin (15.3%) and Tennessee had the highest rate (38.3%).34
The prevalence of resistance to penicillin in the United States has increased steadily over the past decade.
5
10
12
15
A nationwide surveillance program sponsored by the CDC detected high-grade resistance to penicillin in only 0.02% of pneumococci isolated from 1979 to 1987.35
By 1988, 0.2% of strains were highly resistant.36
After 1989, however, resistance increased substantially, as outlined in Table 1. This dramatic rise in penicillin resistance during the past decade is indeed worrisome and requires that clinicians at least consider initially prescribing antimicrobial agents effective against resistant strains of S pneumoniae routinely for empirical initial treatment of severely ill patients with CAP. Once the causative organism is identified and susceptibilities are known, antibiotics could be changed based on this information and the clinical response.Table 1Evolution of Penicillin Resistance in Streptococcus pneumonias in the United States
| Source | Study years | No. of isolates | Pel or Pc-R S pneumoniae isolates (%) | Pc-R S pneumoniae isolates (%) |
|---|---|---|---|---|
| Spikaetal, 35 1991 | 1979-87 | 5459 | 5.0 | <0.01 |
| Jorgensen et al, 36 1990 | 1987-89 | 487 | 4 I | 0.2 |
| Breiman et al, 37 1994 | 1991-92 | 544 | 6.6 | 1 3 |
| Barry etal, 38 1994 | 1992-93 | 799 | 22.2 | 7.3 |
| Butler et al, 39 1996 | 1993-94 | 740 | 14.0 | 3.2 |
| Doern et al, 40 1996 | 1994-95 | 1524 | 23.6 | 9.5 |
| Thornsberry et al, 41 1998 | 1996-97 | 9190 | 34.0 | 14.0 |
| Doemetal, 10 1998 | 1997 | 845 | 43.8 | 16.0 |
* Pc-I = intermediate resistance to penicillin; Pc-R = high resistance to penicillin.
Risk Factors
Endemic foci and person-to-person transmission of clones of penicillin-resistant strains have been documented within daycare centers, hospitals, nursing homes, homeless shelters, and correctional facilities.
8
14
15
32
42
43
Prior antibiotic use is the dominant risk factor associated with antimicrobial-resistant pneumococci.15
, 27
Risk factors for colonization with resistant pneumococci include prior antibiotic use, age younger than 6 years, and attendance in daycare centers.5
, 14
, 15
, 42
, 43
, 44
, 45
Risk factors for penicillinresistance among invasive pneumococcal infections include prior β-lactam use, residence in nursing homes or recent hospitalization, and underlying immunosuppressive disease.
14
42
46
47
OTHER DRUG RESISTANCE IN S PNEUMONIAE
Cephalosporins
Resistance to other β-lactam antibiotics increases in parallel with penicillin resistance.
5
8
10
Resistance to cephalosporins arises via alterations of PBPs 2x, 2b, and la, which result in reduced affinity for cephalosporins48
Among penicillin-resistant isolates, the activity of firstand second-generation cephalosporins is often POOr, but third-generation cephalosporins (cefotaxime and ceftriaxone) usually retain adequate activity.8
10
12
32
In some areas, however, up to 40% of S pneumoniae are resistant to cefotaxime and ceftriaxone.5
8
10
45
A 1994 CDC survey found that, overall, 4.1% of S pneumoniae had intermediate resistance and 0.4% had high resistance to cefotaxime.39
In Atlanta, Ga, however, 4% of isolates from invasive pneumococcal infections in 1994 were highly resistant to cefotaxime.5
Cefotaxime-resistantstrains will likely increase in the future because of the high utilization of β-lactam antibiotics.5
48
Carbapenems
Most S pneumoniae, including penicillin-resistant strains, remain susceptible to the carbapenems.
12
49
Meropenem appears to have in vitro activity against penicillin-resistant strains of pneumococci 1 to 2 dilutions higher than imipenem.50
In a recent survey of 971 S pneumoniae strains, 85.9% were inhibited by meropenem at concentrations of 0.12 ug/ml, or lower; all were inhibited at 4 μg/mL or lower.49
Therefore, the carbapenems may play a more important role in the treatment of patients with CAP in whom penicillin-resistant pneumococcus is suspected.Macrolides and Clindamycin
Erythromycin resistance (defined as an MIC >1 µg/ml.) has increased in frequency worldwide, but prevalence rates are highly variable (0%_49%).
3
8
10
13
45
51
In the UnitedStates, only 0.3% of pneumococci from 1979 to 1987 were resistant to macrolides.
35
By 1996, resistance rates of 6% to 15% were found.5
39
More recently, the SENTRY program identified macrolide resistance ranging from 11% to 14% for intermediate resistance and 5% to 7% for high resistance.10
Resistance of S pneumoniae to macrolide antibiotics may develop by several mechanisms. The dominant risk factor is selection pressure from previous antibiotic use.13
15
27
51
Other risk factors for macrolide-resistant S pneumoniae include age younger than 5 years, nosocomial acquisition, and penicillin resistance.3
13
Erythromycin-resistant strains are usually resistant also to clarithromycin, azithromycin, roxithromycin, and several other antibiotic classes.13
15
52
53
Clindamycin resistance occurs less frequently than macrolide resistance in S pneumoniae. In a survey of 1601 isolates of S pneumoniae between November 1997 and April 1998, 1.1% of penicillin-susceptible strains and 12.0% of penicillin-resistant strains were resistant to clindamycin.
29
The presence of high-level resistance to clindamycin (MIC ≥1 μg/ml.) correlated with high-level resistance to macrolides (MIC ≥64 μg/mL).29
Trimethoprim-Sulfamethoxazole
Resistance to TMP-SMX has increased along with penicillin resistance.
5
10
14
45
Recent US studies detected TMP-SMX resistance in 20% to 60% of pneumococcal isolates. Several studies Several studies have found that penicillin-resistant pneumococci are also often resistant to TMP-SMX.5
10
14
Multidrug-resistant strains of S pneumoniae are even more likely to be resistant to TMP-SMX.14
Thus, TMP-SMX is unreliable empirical therapy for patients with CAP.Tetracyclines
Resistance to tetracyclines has increased worldwide, but the prevalence is highly variable (3%-82%).
5
10
14
39
45
In the United States, the level of tetracycline resistance has remained relatively stable (2%-10%) from 1979 to 1994, which likely reflects limited use of this class of antimicrobials for routine treatment of respiratory infections.10
39
Given the relatively low cost and low incidence of resistance, doxycycline has been increasingly advocated as reasonable therapy for CAP.54
Fluoroquinolones
Historically, the fluoroquinolones (eg, ciprofloxacin, ofloxacin) were considered poor choices for severe CAP because of their marginal MIC (1.0-2.0µ g/mL) against S pneumoniae.
15
Levofloxacin has more desirable pharmacokinetics compared with ofloxacin.55
56
and the newer fluoroquinolones (eg, gatifloxacin, moxifloxacin) have improved activity against S pneumoniae, making them better choices for treatment of CAP.18
55
, 56
, 57
, - Baquero F
- Garcia-Rodriguez JA
- Garcia de Lomas J
- Aguilar L
Spanish Surveillance Group for Respiratory Padtogens. Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients with respiratory tract infections in Spain: results of a I-year (1996-1997) multicenter surveillance study.
Antimicrob Agents Chemother. 1999; 43: 357-359
58
, 59
Importantly, quinolone susceptibilities are usually not affected by resistance to penicillin; resistance to the newer quinolones is rare, even among penicillin-resistant strains of S pne umoniae.7
18
55
57
, - Baquero F
- Garcia-Rodriguez JA
- Garcia de Lomas J
- Aguilar L
Spanish Surveillance Group for Respiratory Padtogens. Antimicrobial resistance of 1,113 Streptococcus pneumoniae isolates from patients with respiratory tract infections in Spain: results of a I-year (1996-1997) multicenter surveillance study.
Antimicrob Agents Chemother. 1999; 43: 357-359
58
, 59
, 60
However, a recent report from the Canadian Bacterial Surveillance Network found that the prevalence of pneumococci with reduced susceptibility to fluoroquinolones increased from 0% in 1993 to 1.7% by 1998. 19 The authors used a fluoroquinolone MIC of 4 µg/ml. or higher as the definition of reduced susceptibilities.
19
The clinical importance of this reduced susceptibility is not known.Vancomycin
All strains of S pneumoniae, even those resistant to penicillin and other antimicrobials, have remained susceptible to vancomycin.
3
10
39
40
Unfortunately, several clinical isolates of S pneumoniae have been identified that are “tolerant” to vancomycin (ie, inhibited but not killed by a concentration of vancomycin 10-fold higher than the MIC for the isolates)20
21
All tolerant isolates were resistant to penicillin.20
Theoretically, just a few mutations could cause these tolerant strains of S pneumoniae to become fully resistant to vancomycin.20
Given this worrisome recent development, new antimicrobials with excellent activity against S pneumoniae need to be developed urgently.Multiple Drugs
Resistance to 2 or more antibiotics (eg, penicillins, cephalosporins, TMP-SMX, macrolides) is defined as multiple-drug resistance.
5
14
15
39
61
Multidrug-resistant strains of S pneumoniae were first noted in South Africa and are now endemic in many countries.5
14
15
Risk factors for multidrugresistant S pneumoniae include prior antibiotic use, extremes of age, and hospitalization.14
15
Of some concern, multiple-drug resistance was found in 9% to 25% of pneumococci in 2 US studies.5
40
VIRULENCE, PRESENTATION, AND PROGNOSIS IN PATIENTS WITH PENICILLIN - RESISTANT S PNEUMONIAE
Virulence, clinical features, and disease presentation are similar for patients presenting with illnesses caused by penicillin-susceptible or penicillin-resistant strains.
3
8
50
However, some factors associated with resistance also worsen prognosis (eg, extremes of age, hospitalization, previous exposure to antibiotics).8
Although data are limited, pneumonia with resistant strains has not been associated with increased mortality, even though penicillins or cephalosporins have been used.3
8
14
50
62
63
Pallares et al8
prospectively reported treatment outcomes in 504 consecutive patients with pneumococcal pneumonia (diagnosis by blood culture in 412, pleural fluid in 46, transthoracic aspiration in 37, and bronchoscopy in 55). Among patients with pneumonia caused by 1 pathogen, the overall percentage of highly penicillin-resistant strains was 10%. The majority of patients were treated with a β-Iactam antibiotic administered intravenously (penicillin, 2 million U every 4 hours; ampicillin, 2 g every 6 hours; ceftriaxone, 1-2 g every 24 hours; or cefotaxime, 1-2 g every 6 hours). Although the overall mortality rate among patients with penicillin-resistant strains was 38% compared with 24% in those with sensitive strains (P=.001), this difference was no longer statistically significant when other predictors of mortality were included (odds ratio, 1.3; P=.32).In a recent study of 101 hospitalized patients with pneumococcal pneumonia, penicillin resistance was identified in 49% of isolates. Antibiotic resistance was not associated with longer hospital stay, severity of pneumonia, and other complications.
64
Mortality due to drug-resistant strains was not greatly increased, and discordant antimicrobial treatment was not associated with attributable mortality.64
Another group of investigators recently evaluated the outcome of 192 adult patients with bacteremic pneumococcal pneumonia.
65
The in-hospital mortality due to pneumonia was higher for patients whose pneumococcal isolates were not susceptible to penicillin compared with those patients with susceptible strains of pneumococci (23% vs 11%; relative risk, 2.1). However, after adjustment for difference in severity of illness, there was no increased risk of death associated with infections due to resistant pneumococci. Suppurative complications of pneumonia, however, did occur more frequently with infections due to resistant strains of pneumococci, even after adjustment for severity of illness.65
This potential discrepancy between in vitro sensitivity and clinical outcome in patients with CAP due to penicillin-resistant S pneumoniae is interesting and may depend more on tissue penetration and accumulation of antibiotics in the infected lung than on the antimicrobial levels which can be achieved in serum.
66
For example, the tissue levels of β-lactam agents may be well above the resistance breakpoints established by the National Committee for Clinical Laboratory Standards.67
With macrolides, which exhibit a similar time-dependent killing of bacteria, a similar process has been suggested to explain the discrepancy.68
The clinical importance of these differences in susceptibility and outcome, however, remains unclear. Thus, the efficacy of β-lactam antibiotics in the treatment of penicillin resistant pneumococci remains controversial, and optimal therapy for serious infections caused by resistant pneumococci has not been clarified. It is quite likely, however, that future studies will be performed with adequate statistical power to detect differences in important clinical outcomes in CAP patients infected with either penicillin-susceptible or penicillin-resistant strains of S pneumoniae.THERAPY
Although the prevalence of antimicrobial resistance in the community is important in choosing antimicrobial therapy, clinicians often do not know the specific etiology of CAP in an individual patient at the time of treatment decisian.
2
4
23
69
Even when a pathogen is isolated, antibiotic susceptibilities are not usually available for at least several hours. Decisions regarding empirical treatment of CAP are often based on institution-specific clinical practice guidelines, which are usually based on guidelines developed by prominent national organizations.23
, 24
, 25
, - Niederman MS
- Bass Jr, JB
- Campbell GD
- et al.
American Thoracic Society, Medical Section of the American Lung Association. Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy.
Am Rev Respir Dis. 1993; 148: 1418-1426
63
, 70
In a recent study of 12,945 elderly patients with CAP, 3 empirical antimicrobial regimens (recommended in the 1993 American Thoracic Society CAP guidelines), which included a secondgeneration cephalosporin plus a macrolide, a third-generation cephalosporin plus a macrolide, or a fluoroquinolone alone, were associated with lower 30-day mortality.71
Another study revealed that additional microbiological studies did not change the outcome in hospitalized patients initially treated with use of the American Thoracic Society guidelines, suggesting the effectiveness of the guideline-based empirical therapy.22
Given the prevalence of resistant pneumococci in patients presenting with CAP, it is important that institutions implement practice guidelines for empirical CAP treatment, taking into consideration treatment effectiveness, future resistance issues, and economic feasibility.If pneumococcal disease is confirmed, penicillins remain the mainstay of therapy for infections due to susceptible strains (eg, penicillin G for parenteral use; highdose amoxicillin, 875 mg twice a day, for oral use).
8
15
61
Oral β-lactam antibiotics may be adequate for mild to moderate infections caused by susceptible strains.15
Of the oral penicillins, amoxicillin is the most active agent against S pneumoniae; the addition of clavulanate to amoxicillin does not improve the activity.15
Of the extended-spectrum penicillins, piperacillin is most active against S pneu moniae15
Among the cephalosporin antibiotics, cefuroxime axetil and cefpodoxime have excellent intrinsic activity against susceptible S pneumoniae (similar to amoxicillin).40
Thus, oral penicillins or cephalosporins may be adequate for mild infections caused by strains that have high or intermediate penicillin susceptibility, but these agents cannot be considered reliable for more serious infections.Optimal therapy for serious pneumococcal infections caused by pneumococci that are penicillin-resistant or have only intermediate susceptibility is controversial.
40
50
61
Although controlled therapeutic trials have not been done, favorable responses have been cited with cefotaxime or ceftriaxone for pneumococcal bacteremia or pneumonia, even for strains that are penicillin-resistant or have only intermediate susceptibility.5
8
32
50
61
63
Interestingly, favorable responses have also been noted with high-dose penicillin, even in bacteremic pneumonia caused by pneumococci that are penicillin-resistant or have only intermediate susceptibility.5
8
32
50
61
63
It should be emphasized that data regarding the efficacy of penicillins or cephalosporins for penicillin-resistant strains are limited, and additional data are required to clarify optimal therapy in this context.Macrolide antibiotics are effective for treatment of CAP caused by susceptible strains of pneumococci. Clarithromycin has more activity than either erythromycin or azithromycin against pneumococci in vitro.
29
72
However, resistance to all macrolides, based on current National Committee for Clinical Laboratory Standards breakpoints, should be assumed among isolates displaying erythromycin resistance. The high prevalence of macrolide resistance in some areas raises concern for the use of macrolides for empirical treatment of serious pneumococcal infections.3
8
13
40
45
63
The newer fluoroquinolones (eg, levofloxacin, gatifloxacin, moxifloxacin) may have a role for infections due to penicillin- or macrolide-resistant pneumococci.
18
55
56
58
Quinolone susceptibilities are generally not affected by susceptibility or resistance to penicillin.18
56
60
Fluoroquinolone monotherapy for patients with CAP has been associated with high cure rates (>90%), even when S pneumoniae was thought to be the causative agent.7
56
73
Enthusiasm for fluoroquinolones should be tempered, however, by the potential for evolution of antimicrobial resistance.19
For highly resistant pneumococci, vancomycin may be used for treatment of pneumonia, as all strains of pneumococci (both penicillin-susceptible and penicillin-resistant) remain susceptible to vancomycin.
5
8
13
39
40
However, given the concern for the development and spread of vancomycin resistance in pneumococci and other gram-positive cocci, this antibiotic must be used cautiously.11
20
21
74
The newly released oxazolidinone linezolid has good in vitro activity against those strains both susceptible and not susceptible to it and may have a use in the treatment of S pneumoniae caused by resistant strains.Carbapenems, both imipenem-cilastatin and meropenem, are highly active against both penicillin-susceptible and penicillin-resistant strains.
5
12
13
74
Meropenem has been approved for treatment of bacterial meningitis. Clinical studies of these agents to treat serious pneumococcal infections are limited. Given their broad spectrum of antibacterial activity and increased incremental costs compared with other potential agents, studies rigorously evaluating their use for appropriate empirical treatment of CAP are needed.SUMMARY AND CONCLUSIONS
Streptococcus pneumoniae resistance to available antimicrobial agents is an important clinical problem, the magnitude of which is projected to worsen. The most common resistance is that to penicillin, with prevalence rates reaching 45% in some geographical areas. Maybe more worrisome than the penicillin experience are the emerging resistance patterns of this organism to several other previously effective antimicrobial classes. Decelerating the rate of antibiotic resistance is particularly problematic because of the fact that development of future resistance correlates substantially with current antibiotic use. Thus, a clear tradeoff is recognized between choosing an effective therapy now and the resultant pressure for future resistance as broad-spectrum agents are more frequently used empirically for patients with CAP. At present, no method to stop this vicious cycle has emerged. However, an evidence-based approach can minimize the tension between optimizing care for an individual patient today and ensuring effective therapy for future patients with S pneumoniae infection. Increasing the appropriate use of antibiotics is essential for success. For those patients with indications for antibiotic therapy, practice guidelines should be implemented that take into account both patient characteristics and local resistance patterns. Further studies that include clinical effectiveness, future resistance patterns, and economic impact to define the optimal treatment of CAP due to S pneumoniae are warranted.
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© 2000 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
