A comparative clinical study of pneumonia by penicillin-resistant and -sensitive Streptococcus pneumoniae in a community hospital

OBJECTIVE: This study aimed to determine the clinical difference of pneumonia between penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae. METHODOLOGY: Forty-nine cases in 46 patients of pneumococcal pneumonia were studied from December 1992 to May 1997. There were 24 cases (in 22 patients) of penicillin-resistant pneumococci (PRSP) pneumonia which were compared with 25 cases (in 24 patients) with penicillin-sensitive pneumococci (PSSP). RESULTS: Both the mean age and the underlying disease states did not differ between the two groups. However, hospital-acquired pneumonia and previous use of antibiotics were observed in eight (33.3%) and 12 (50.0%) patients in PRSP compared with three (12.0%) and two (8.0%) in PSSP, respectively. The clinical efficacy rate and bacteriological eradication rates were 87.5 and 87.5% in PRSP compared with 87.5 and 87.0% in PSSP, respectively. Minimum inhibitory concentration (MIC) of antibiotics against 30 pneumococcal isolates was examined, and 10 strains ranged from 0.10-0.78 microg/mL and five strains were more than 1.56 microg/mL against penicillin G, while the MIC showed higher resistance to other antibiotics except for the carbapenems. Serotyping of the isolates by antiserum revealed differences in the predominant types PRSP (19F) and PSSP (6A,9V) [corrected]. CONCLUSIONS: We must care for not only community-acquired infection but also nosocomial transmission of PRSP pneumonia. Most patients with infections due to PRSP tended to have a milder illness with a good outcome (no patient died). As such it appears that empiric therapy for pneumococcal pneumonia does not require modification from what is recommended at present. However, in patients with infection due to highly resistant strains, and who are not responding to conventional therapy should have their treatment modified according to subsequent susceptibility testing.     

Risk factors and clinical outcomes of penicillin resistant S. pneumoniae community-acquired pneumonia in Khon Kaen, Thailand

To determine the prevalence, risk factors and clinical outcomes of penicillin-resistant S. pneumoniae (PRSP) in community-acquired pneumonia (CAP), a cross-sectional study was conducted between January 1995 and December 2004 at Srinagarind Hospital, Khon Kaen, Thailand. Patients hospitalized with CAP and culture proved to be S. pneumoniae were included. PRSP was found in 22 of 64 (34.4%) patients. The MIC levels of penicillin non-susceptible strains ranged between 0.25 and 0.75 microg/ml. Resistance to other antibiotics ranked: cotrimoxazole (51.6%), tetracycline (26.6%), erythromycin (20.6%), lincomycin (18.7%), chloramphenicol (12.5%) and ampicillin (1.6%). None of the isolates was resistant to cephalothin. The significant risk factors for PRSP infection were previous antibiotic use within 3 months (Adjusted OR 40.83, 95% CI 3.71 to 449.41) and alcoholism (Adjusted OR 8.82, 95% 1.25 to 62.46). Bacteremia and empyema thoracis were found more commonly in PRSP than PSSP infection, but not statistically significant. Pneumonia-related mortality was nearly the same, PRSP 9.1% vs PSSP 9.5% (p = 0.96). The reason why the clinical outcomes of these two groups were not different may be the patients were infected with mildly resistant organisms. Thus, pneumonia caused by intermediate-level penicillin resistant S. pneumoniae appears to be adequately treated with beta-lactams or aminopenicillin antibiotics. The MIC levels of penicillin resistance should be monitored further. The need for antibiotics active against drug-resistant S. pneumoniae was required if high-level penicillin resistance was detected.     

Epidemiological survey of pneumococcus serotypes in pediatric patients with acute suppurative otitis media

To determine the distribution of Streptococcus pneumoniae serotypes isolated from patients under 6 years of age with acute suppurative otitis media, to calculate the serotype coverage of 7-valent pneumococcal conjugate vaccine, and to clarify trends in PCG-resistant Streptococcus pneumoniae, we conducted a one-year prospective study from April 2005 to March 2006 at 10 medical institutions in Hokkaido, Miyagi, Chiba, Tokyo, Kanagawa, and Mie, Japan. Specimens collected by tympanotomy or myringotomy numbered 856, and 691 strains were isolated from 599 specimens. Of these, 219 isolates (31.7%) were identified as Streptococcus pneumoniae and 201 met study requirements. The most common serotype was 19F (52 isolates, 25.9%), followed by 6B (30 isolates, 14.9%) and 23F (24 isolates, 11.9%). Seven-valent vaccine serotype coverage was 62.7%. The percentage of PSSP was 40.3%, PISP 42.8%, and PRSP 16.9%, resistant strains (PISP and PRSP) combined accounted for 59.7%. Seven-valent vaccine serotype coverage for PISP was 80.2% and PRSP 82.4%. PBP gene mutation was observed in 175 isolates (87.1%), including 70 of gPISP (34.8%) and 105 of gPRSP (52.2%). Gene mutation induced by macrolides was found in 176 isolates (87.6%).     

Meningitis in a Canadian adult due to high level penicillin-resistant, cefotaxime-intermediate Streptococcus pneumoniae

Invasive penicillin-resistant pneumococcal (PRSP) infections are increasing worldwide. In Canada, the incidence of penicillin resistance among Streptococcus pneumoniae isolates is estimated at greater than 6%. In Quebec, only one case of PRSP meningitis has been reported and involved an infant. An adult patient is described who presented with meningitis caused by high level penicillin-resistant, cefotaxime-intermediate S pneumoniae.     

Resistance to antimicrobiotics and mutation of PBPs in Streptococcus pneumoniae isolated from Kinki region of Japan

We studied the susceptibility to penicillin G (PCG) and other antimicrobiotics in 235 clinical isolates of Streptococcus pneumoniae. Samples were collected between April 1 and June 30, 2000 from nine medical institutions of the Kinki Region of Japan. We classified the minimum inhibitory concentration (MIC) of PCG according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria. The overall rate of all types of S. pneumoniae resistance was 53.2% (penicillin-susceptible S. pneumoniae (PSSP): 46.8%, penicillin-intermediate S. pneumoniae (PISP): 42.6%, penicillin-resistant S. pneumoniae (PRSP): 10.6%). In other antimicrobiotics, the resistance (R)/intermediate susceptibility (I) rates (R/I%) were as follows: ceftriaxone, 28.9%; cefotaxime, 7.7%; imipenem, 8.9%; meropenem, 9.8%; clarithromycin, 82.6%; clindamycin, 42.1%; levofloxacin, 0.4%; vancomycin, 0%. We used the polymerase chain reaction to study the mutations of the penicillin-binding proteins pbp1 a, pbp2b, and pbp2x in 140 strains of S. pneumoniae in the MIC for PCG was < 0.5 microgram/ml. Among the 109 strains of PSSP, 32 (29.4%) had no mutation and 77 (70.6%) showed mutation of more than one of the pbp mutations. Among the 31 strains of PISP, only 1 strain (3.2%) was not mutated. Since 70.6% of the strains classified as PSSP had pbp mutations, S. pneumoniae clearly can acquire resistance to anti-microbiotics. In the future, a comprehensive surveillance of S. pneumoniae is necessary.     

Risk factors for penicillin-resistant Streptococcus pneumoniae acquisition in patients in Bangkok.

To identify risk factors for acquisition of penicillin-resistant Streptococcus pneumoniae (PRSP) in patients in Bangkok, using a case-control study, the study included patients with clinical specimens which grew S. pneumoniae during January to December 1997, treated at a teaching hospital in Bangkok. Penicillin susceptibility was determined by E-test and strains with MIC of > 0.1 microg/ml were considered resistant. Cases were the patients who had PRSP, and patients who had penicillin-susceptible S. pneumoniae (PSSP) were controls. The study variables included age 15 years or younger, immunocompromised status, ventilatory support, and antibiotic use or hospitalization within the previous 3 months. There were 73 cases and 51 controls. Their ages were 0 to 87 years, with median age of cases 4 and controls 49 years. Pneumonia was the most common type of infection, being 47% in cases and 45% in controls. Univariate analysis revealed significant association of PRSP acquisition with previous antibiotic use (p<0.0001), age < or = 15 years (p=0.001) and previous hospitalization (p=0.002). Logistic regression analysis in order to adjust for confounding effects showed that the only significant risk factor was previous antibiotic use (OR 18.4; 95% CI 6.2-54.6). The major risk factor for acquisition of PRSP in this study population is recent antibiotic use. Decreased antibiotic use would reduce risk of acquisition of PRSP.     

Serotype distribution and penicillin-binding protein genes of Streptococcus pneumoniae in children with invasive pneumococcal infection

Between August 1998 and July 2005, we studied the serotypes and mutation of penicillin-binding protein (PBP) genes of 46 strains of Streptococcus pneumoniae isolated from children with invasive pneumococcal infection in Hokkaido. The clinical diagnosis was pneumonia in 16 cases, occult bacteremia in 15, meningitis in 8, upper respiratory infection in 6, and arthritis in 1. Patients ranged in age from 2 months to 9 years old. Prevalent serotypes were 6B (39.1%), 23F (17.4%) 6A (8.7%), and 19F (8.7%). The serotype coverage rate by the 7-valent pneumococcal vaccine was greater than 70% in children. Mutation of 3 genes (Penicillin-binding S. pneumoniae, PRSP) was detected in 18 isolates, mutation of 10 genes (pbp1a and pbp2x, or pbp2x and pbp2b) in 2, and of pbp2x alone in 15. PRSP was found in serotypes 6A, 6B, and 23F, and the rate of PRSP in 6A, 6B, and 23F was 75.0%, 62.5%, and 55.6%, respectively.     

Streptococcus pneumoniae growth based on drug resistance genotype

Marked Streptococcus pneumoniae tolerance is attributed to a penicillin and macrolide resistance genotypes, yet no report has, to our knowledge, compared the ability of these two genotypes to grow. Deviations in the number of clinical appearances of Streptococcus pneumoniae depend on the combination of these genotypes, thought primarily due to the individual strain growth. To test this, we compared ATCC6303 and a strain of each genotype with an absorption spectrophotometer. Time points-T0, T2, T4, T8, T10, T12, and T24-were compared to each of the following factors: initial value, dullness time, doubling time (D.B.T.), peak attainment, peak value, and stationary value. ATCC6303 and the clinical strain (PSSP8) showed no difference in time points or tested factors. Penicillin susceptible Streptcoccus pneumoniae (PSSP) 8 and Penicillin intermediately resistant Streptcoccus pneumoniae (PISP) (2b, mefA) strains showed significant differences in some time pointsT8, T10, and T12-and in certain factors-dullness time, D.B.T., and peak attainment-. In penicillin-resistant genotypes, the sequential growth rate priority was PSSP>PISP>PRSP, while in macrolide-resistant genotypes, it was mefA>non-mefA, and non-ermB>ermB. PISP (2x) and PISP (2x+2b, mefA) begin doubling immediately, suggesting that they proliferate earlier than other strains. Differences in the start of doubling time and doubling speed suggest that different strains are distributed among clinical resistant S. pneumoniae strains.     

Pneumococcal and Haemophilus influenzae meningitis in a children's hospital in Ethiopia: serotypes and susceptibility patterns

Streptococcus pneumoniae and Haemophilus influenzae are responsible for most pyogenic meningitis cases in children in Ethiopia. Resistance of S. pneumoniae and H. influenzae to penicillin and chloramphenicol respectively has been reported globally. Resistance has been related to specific serotypes of S. pneumoniae or to beta-lactamase-producing H. influenzae strains. This study describes the serotypes/ serogroups and susceptibility pattern of the two organisms causing meningitis in Ethiopian children. There were 120 cases of meningitis caused by S. pneumoniae (46) and H. influenzae (74) over a period of 3 years (1993-95). Nineteen children died from pneumococcal and 28 from haemophilus meningitis. Penicillin-resistant pneumococcal meningitis (4/8 = 50%) caused a greater mortality rate than penicillin-susceptible pneumococcal meningitis (15/38 = 39%). Common serotypes accounting for 76% of S. pneumoniae were type 14, 19F, 20, 1, 18 and 5; and serotypes 14, 19F and 7 (accounting for 17% of strains) showed intermediate resistance to penicillin G. 97% of the H. influenzae isolates were type b, and in only two cases beta-lactamase-producing. 72% of isolates of the S. pneumoniae we identified belong to serotypes preventable by a 9-valent vaccine. Our study highlights the possibility of resistant pyogenic meningitis in children in Ethiopia due to emerging resistant strains of S. pneumoniae and H. influenzae isolates.     

Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae in the Kinki District]

In the Kinki District (Hyogo area, Osaka City area, Osaka Outskirts area, Nara area and Wakayama area), a questionnaire survey of 30 institutions was conducted for methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Median number of their bed was 500 ranging 0 to 1076, 3239 (56%) of the 5815 strains of S. aureus were methicillin-resistant. Although no different prevalence was found among the areas, they were predominantly isolated from sputum of inpatients more than from outpatients, 336 (44%) of the 763 strains of S. pneumoniae were penicillin-resistant. The prevalence rate was the highest in the outpatients in Osaka outskirts. Almost all strains of MRSA were sensitive to vancomycin (VCM) and sulfamethoxazole trimethoprim (ST). Resistant strains were observed in 2% against arbekacin, 6% against amikacin, 44% against minocycline (MINO), and in 54% against gentamicin (GM). Almost all strains of PRSP were sensitive to VCM and ST. Resistant strains were observed in 75% against erythromycin, 50% against MINO, and 75% against GM. This survey identified the trend of hospital infection for MRSA and community infection for PRSP, and sensitive drugs for the treatment.     

Antimicrobial resistance in Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharynx in children

The aims of this study are to investigate the antimicrobial susceptibility of bacteria isolated from children and clarify the risk factors for the carriage of the resistant strains. We examined the minimum inhibitory concentrations (MICs) of antimicrobial agents against 949 strains of Streptococcus pneumoniae (S. pneumoniae) and 791 strains of Haemophilus influenzae (H. influenzae) isolated at our department between September, 2001 and May, 2003. Of those, 226 S. pneumoniae strains and 115 H. influenzae strains were analysed for the resistance genes. Also we retrospectively reviewed the profiles of 1,359 patients with either S. pneumoniae, H. influenzae, or both in nasopharynx. From the view point of MICs, PSSP strains were 185 (19%), PISP strains were 443 (47%), and PRSP strains were 321 (34%) in 949 S. pneumoniae strains, and BLNAS strains were 545 (69%), low-BLNAR strains were 104 (13%), BLNAR strains were 81 (11%), and BLPAR strains were 61 (8%) in 791 H. influenzae strains. The results of gene analysis showed that all resistant strains by MICs such as PISP, PRSP, BLNAR, and BLPAR had resistant genes and that 55% of and 21% of susceptible strains of S. pneumoniae (PSSP) and H. influenzae (BLNAS), respectively, had resistant genes. From the investigation for profiles of 1,359 patients, age less than 3 years old, day nursery, and use of antimicrobial agents in last 3 month, seemed to be the risk factors for carriage of resistant strains. To prevent the resistant bacteria from disseminating we should re-consider how to use the antimicobial agents and nurse the young children.     

331株肺炎链球菌的耐药性及基因分型

目的 了解杭州地区肺炎链球菌临床株的耐药性及青霉素耐药株的分子流行病学特征。方法 用Etest法测定菌株对青霉素的最低抑菌浓度(MIC)，用纸片扩散法测定肺炎链球菌对其他8种抗生素的耐药情况。并以盒式聚合酶链反应(PCR)和青霉素结合蛋白(PBP)基因指纹等分子生物学方法分析菌株间的亲缘关系。结果临床分离得到肺炎链球菌331株，Etest法测得55株(16．6％)青霉素高度耐药株(PRSP)，127株(38．4％)青霉素中度耐药株(PISP)。纸片扩散法测得氨苄西林、复方新诺明、红霉素、四环素、利福平、氯霉素的耐药率分别为1．2％、47．7％、90％、84．3％、0．3％及13％。所有菌株对氧氟沙星、万古霉素敏感。保存存活的35株PRSP可分为17种盒式-PCR谱型，PBP2X、PBP2B、PBP1A的指纹各为5种、7种、5种。盒式谱型A、H的菌株其耐药谱、MIC值和PBP基因指纹高度一致。结论杭州地区肺炎链球菌临床株的青霉素耐药率较高，非β-内酰胺类红霉素、四环素、复方新诺明的耐药率亦较高。杭州地区可能有耐药克隆的流行。     

Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential

By use of multilocus sequence typing, Streptococcus pneumoniae isolates causing invasive disease (n=150) were compared with those from nasopharyngeal carriage (n=351) among children in Oxford. The prevalence of individual clones (sequence types) and serotypes among isolates from invasive disease was related to their prevalence in carriage, and an odds ratio (OR) for invasive disease was calculated for the major clones and serotypes. All major carried clones and serotypes caused invasive disease, although their ability to do so varied greatly. Thus, 2 serotype 14 clones were approximately 10-fold overrepresented among disease isolates, compared with carriage isolates, whereas a serotype 3 clone was approximately 10-fold underrepresented. The lack of heterogeneity between the ORs of different clones of the same serotype, and analysis of isolates of the same genotype, but different serotype, suggested that capsular serotype may be more important than genotype in the ability of pneumococci to cause invasive disease.     

Report of questionnaire survey for methicillin-resistant Staphylococcus aureus and penisillin-resistant Streptococcus pneumoniae between 1998 and 2000 in the Kinki district

Kinki Infection Working Group made an annual (1998-2000) comparative study of an epidemiological investigation for Staphylococcus aureus and Streptococcus pneumoniae in the Kinki district. The number of S. aureus and methicillin-resistant S. aureus (MRSA) isolated decreased for three years, but the isolation frequencies of MRSA has not changed which was approximately 60%. All strains of MRSA were not resistant to vancomysin (VCM) and teicoplanin (TEIC), and the frequencies of resistance to sulfamethoxazole-trimethoprim (ST) and arbekacin (ABK) were 0.1 to 0.7% and 1.9 to 3.1%, respectively. On the other hand, the number of S. aureus and penicillin-resistant S. pneumoniae (PRSP) isolated did not show a consistent tendency, but the isolation frequencies of PRSP has increased for three years. All strains of PRSP were sensitive to vancomycin (VCM), but the frequencies of resistance to cefaclor and other some antibiotics have increased.     

Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae

Resistance to penicillin in clinical isolates of Streptococcus pneumoniae has occurred by the development of altered penicillin-binding proteins (PBPs) that have greatly decreased affinity for the antibiotic. We have investigated the origins of penicillin-resistant strains by comparing the sequences of the transpeptidase domain of PBP2B from 6 penicillin-sensitive and 14 penicillin-resistant strains. In addition we have sequenced part of the amylomaltase gene from 2 of the sensitive and 6 of the resistant strains. The sequences of the amylomaltase gene of all of the strains and of the PBP2B gene of the penicillin-sensitive strain show that S. pneumoniae is genetically very uniform. In contrast the PBP2B genes of the penicillin-resistant strains show approximately equal to 14% sequence divergence from those of the penicillin-sensitive strains and the development of penicillin resistance has involved the replacement, presumably by transformation, of the original PBP2B gene by a homologous gene from an unknown source. This genetic event has occurred on at least two occasions, involving different sources, to produce the two classes of altered PBP2B genes found in penicillin-resistant strains of S. pneumoniae. There is considerable variation among the PBP2B genes of the resistant strains that may have arisen by secondary transformation events accompanied by mismatch repair subsequent to their original introductions into S. pneumoniae.     

Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae

Penicillin-resistant strains of Streptococcus pneumoniae possess altered forms of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. The PBP2B genes of these strains have a mosaic structure, consisting of regions that are very similar to those in penicillin-sensitive strains, alternating with regions that are highly diverged. Penicillin-resistant strains of viridans groups streptococci (e.g., S. sanguis and S. oralis) that produce altered PBPs have also been reported. The PBP2B genes of two penicillin-resistant clinical isolates of S. sanguis were identical in sequence to the mosaic class B PBP2B genes found in penicillin-resistant serotype 23 strains of S. pneumoniae. Emergence of penicillin resistance appears to have occurred by the horizontal transfer of an altered PBP2B gene from penicillin-resistant S. pneumoniae into S. sanguis. The PBP2B genes of three penicillin-resistant S. oralis strains were similar to the mosaic class B PBP2B gene of penicillin-resistant strains of S. pneumoniae but possessed an additional block of diverged sequence. Penicillin resistance in S. oralis has also probably arisen by horizontal transfer of this variant form of the class B mosaic PBP2B gene from a penicillin-resistant strain of S. pneumoniae.     

Intercontinental spread of a multiresistant clone of serotype 23F Streptococcus pneumoniae.

Isolates of serotype 23F Streptococcus pneumoniae with high levels of resistance of penicillin have been commonly recovered in Spain for more than a decade. Recently penicillin-resistant serotype 23F S. pneumoniae strains were also isolated from children attending a day-care center in Cleveland. A number of Spanish and Cleveland isolates were compared by electrophoretic analysis of penicillin-binding protein (PBP) profiles and DNA restriction endonuclease cleavage profiles of the PBP 2X and 2B genes amplified with the polymerase chain reaction and by multilocus enzyme electrophoresis. All strains were identical by these criteria. The findings demonstrate that the Spanish and Cleveland isolates are clonally related and suggest that this antibiotic resistant clone of serotype 23F S. pneumoniae has spread intercontinentally from Spain to the United States.     

Sequential colonization by Streptococcus pneumoniae of healthy children living in an orphanage

A prospective study of nasopharyngeal colonization by Streptococcus pneumoniae in the exceptional conditions of a closed community of abandoned children was done over a 1-year period; 71 children (age <24 months) were studied monthly. S. pneumoniae was isolated from 58 (81.7%), and 94.5% of the 111 isolates were resistant to penicillin. The mean rate of carriage was estimated at 57.4%, ranging from 42.8% to 70.4%. Children were sequentially colonized by a mean of 3 different isolates. The mean duration of carriage for a given isolate was approximately 2.2 months. Serotyping and molecular typing by pulsed-field gel electrophoresis showed that children were colonized by a limited number of clones belonging to only 4 serotypes and 4 pulsotypes. These clones rapidly spread in the community and colonized the children in waves, with a rapid turnover of S. pneumoniae isolates, facilitated by close contact between children.     

Molecular epidemiology of Streptococcus pneumoniae causing invasive disease in 5 countries

A multicenter study was done during 1993-1995 to investigate prospectively the influence of several prognostic factors for predicting the risk of death among patients with pneumococcal bacteremia. Five centers located in Canada, the United Kingdom, Spain, Sweden, and the United States participated. Clinical parameters were correlated to antibiotic susceptibility and serotyping of the 354 invasive pneumococcal isolates collected and to molecular typing of 173 isolates belonging to the 5 most common serotypes (14, 9V, 23F, 3, and 7F). Serotype 14 was the most common among all isolates, but serotype 3 dominated in fatal cases and in isolates from Spain and the United States, the countries with the highest case-fatality rates. Fewer different patterns were found among the type 3 isolates, which suggests a closer clonal relationship than that among isolates belonging to other serotypes. Of type 3 isolates from fatal cases, 1 clone predominated. Other penicillin-susceptible invasive clones were also shown to spread in and between countries.     

Population snapshot of emergent Streptococcus pneumoniae serotype 19A in the United States, 2005

BACKGROUND: Serotype 19A invasive pneumococcal disease (IPD) increased annually in the United States after the introduction of the 7-valent conjugate vaccine (PCV7). To understand this increase, we characterized serotype 19A isolates recovered during 2005. METHODS: IPD cases during 1998-2005 were identified through population-based surveillance. We performed susceptibility testing and multilocus sequence typing on 528 (95%) of 554 serotype 19A isolates reported in 2005. RESULTS: The incidence of IPD due to serotype 19A increased from 0.8 to 2.5 cases per 100,000 population between 1998 and 2005 (P < .05), whereas the overall incidence of IPD decreased from 24.4 to 13.8 cases per 100,000 population (P < .05). Simultaneously, the incidence of IPD due to penicillin-resistant 19A isolates increased from 6.7% to 35% (P < .0001). Of 151 penicillin-resistant 19A isolates, 111 (73.5%) belonged to the rapidly emerging clonal complex 320, which is related to multidrug-resistant Taiwan(19F)-14. The remaining penicillin-resistant strains were highly related to other clones of PCV7 serotypes or to isolates within major 19A clonal complex 199 (CC199). In 1999, only CC199 and 3 minor clones were apparent among serotype 19A isolates. During 2005, 11 multiple-isolate clonal sets were detected, including capsular switch variants of a serotype 4 clone. CONCLUSIONS: PCV7 ineffectiveness against serotype 19A, antibiotic resistance, clonal expansion and emergence, and capsular switching have contributed to the genetic diversity of 19A and to its emergence as the predominant invasive pneumococcal serotype in the United States.