• No results found

Clinical Characteristics and Outcome of Children With Pneumonia Attributable to Penicillin-susceptible and Penicillin-nonsusceptibleStreptococcus pneumoniae

N/A
N/A
Protected

Academic year: 2020

Share "Clinical Characteristics and Outcome of Children With Pneumonia Attributable to Penicillin-susceptible and Penicillin-nonsusceptibleStreptococcus pneumoniae"

Copied!
9
0
0

Loading.... (view fulltext now)

Full text

(1)

Clinical Characteristics and Outcome of Children With Pneumonia

Attributable to Penicillin-susceptible and Penicillin-nonsusceptible

Streptococcus pneumoniae

Tina Q. Tan, MD*; Edward O. Mason Jr, PhD‡; William J. Barson, MD§; Ellen R. Wald, MDi; Gordon E. Schutze, MD¶; John S. Bradley, MD#; Moshe Arditi, MD**; Laurence B. Givner, MD‡‡;

Ram Yogev, MD*; Kwang Sik Kim, MD**; and Sheldon L. Kaplan, MD‡

ABSTRACT. Objective. To compare the clinical char-acteristics, treatment, and outcome of pediatric patients with pneumonia attributable to isolates ofStreptococcus pneumoniae that were either susceptible or nonsuscep-tible to penicillin.

Design. Multicenter, retrospective study.

Setting. Eight children’s hospitals in the United States.

Participants. Two hundred fifty-four children with pneumococcal pneumonia identified from patients en-rolled in the United States Pediatric Multicenter Pneu-mococcal Surveillance Study during the 3-year period from September 1, 1993 to August 31, 1996.

Outcome Measures. Demographic and clinical vari-ables including necessity for and duration of hospital-ization, frequency of chest tube placement, antimicrobial therapy, susceptibility of isolates, and clinical outcome.

Results. There were 257 episodes of pneumococcal pneumonia that occurred in 254 patients. Of the 257 iso-lates, 22 (9%) were intermediate and 14 (6%) were resis-tant to penicillin; 7 (3%) were intermediate to ceftriaxone and 5 (2%) were resistant to ceftriaxone. There were no differences noted in the clinical presentation of the pa-tients with susceptible versus nonsusceptible isolates. Twenty-nine percent of the patients had a pleural effu-sion. The 189 (74%) hospitalized patients were more likely to have an underlying illness, multiple lung lobe involvement, and the presence of a pleural effusion than nonhospitalized patients. Fifty-two of 72 hospitalized patients with pleural effusions had a chest tube placed, and 27 subsequently underwent a decortication drainage procedure. Eighty percent of the patients treated as out-patients and 48% of the inout-patients received a parenteral second or third generation cephalosporin followed by a course of an oral antimicrobial agent. Two hundred forty-eight of the patients (97.6%) had a good response to therapy. Six patients died; however, only 1 of the deaths was related to the pneumococcal infection.

Conclusion. The clinical presentation and outcome of therapy did not differ significantly between patients with penicillin-susceptible versus those with nonsuscep-tible isolates ofS pneumoniae. Hospitalized patients were more likely to have underlying illnesses, multiple lobe involvement, and the presence of pleural effusions than patients who did not require hospitalization. In other-wise normal patients with pneumonia attributable to penicillin-resistant pneumococcal isolates, therapy with standardb-lactam agents is effective.Pediatrics1998;102: 1369 –1375;pediatrics, pneumococcal pneumonia, penicil-lin-resistance.

ABBREVIATIONS. CXR, chest radiograph; WBC, white blood cell; MIC, minimal inhibitory concentration.

S

treptococcus pneumoniae,the most common bac-terial pathogen causing community-acquired pneumonia in both adults and children, results in an estimated 500 000 cases of pneumonia each year.1During the last decade, isolates ofS pneumoniae that are resistant to penicillin and other antibiotics have continued to become more frequent.2,3The im-pact that this has had on the treatment of pneumo-coccal pneumonia is unclear.

The typical clinical presentation and outcome of pneumococcal pneumonia in adults has been well-described; however, there are little data concerning the clinical characteristics of pneumococcal pneumo-nia in children, especially in the era of increasing antimicrobial resistance.4,5Friedland and colleagues,6 compared various clinical characteristics in 78 South African children with pneumococcal pneumonia (25 with isolates intermediate to penicillin), and found no difference in the outcome of those children who had penicillin-susceptible versus those with nonsus-ceptible isolates. Except for small case series or indi-vidual case reports, no other studies have focused on the outcome of pneumococcal pneumonia attribut-able to antibiotic-resistant isolates in children. The purpose of our study was to compare the clinical characteristics, treatment, and outcome of pneumo-coccal pneumonia in pediatric patients with isolates ofS pneumoniaethat were either susceptible or non-susceptible to penicillin.

MATERIALS AND METHODS

The United States Pediatric Multicenter Pneumococcal Surveil-lance Study Group is comprised of eight children’s hospitals in the From the Pediatric Infectious Disease Sections of *Northwestern University

Medical School, Chicago, Illinois; ‡Baylor College of Medicine, Houston, Texas; §Ohio State University College of Medicine, Columbus Ohio;i Uni-versity of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; ¶Uni-versity of Arkansas for Medical Sciences, Little Rock, Arkansas; #Children’s Hospital of San Diego and the University of California–San Diego School of Medicine, San Diego, California; **University of Southern California School of Medicine, Los Angeles, California; and ‡‡Bowman Gray School of Med-icine of Wake Forest University, Winston-Salem, North Carolina. Received for publication Dec 17, 1997; accepted May 13, 1998.

(2)

following cities: Houston, TX; Pittsburgh, PA; Chicago, IL; Colum-bus, OH; Los Angeles, CA; Little Rock, AR; San Diego, CA; and

Winston-Salem, NC. Children with pneumonia attributable toS

pneumoniaewere identified prospectively from patients with sys-temic infections enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study between September 1, 1993 and August 31, 1996. The diagnosis of pneumococcal pneumonia was based on chest radiograph (CXR) findings and a positive blood and/or pleural fluid culture.

A standardized data form was completed retrospectively for each episode. Information collected included: date of birth; gen-der; race; date of infection; underlying illness; presenting signs, symptoms, and findings on physical examination; peripheral white blood cell (WBC) count and differential; CXR findings (in-cluding the presence of pleural effusion); whether hospitalized;

duration of hospitalization; duration of fever and oxygen (O2)

requirement for hospitalized patients; chest tube placement and duration; performance of other invasive procedures; antimicrobial therapy; follow-up CXR results; and clinical response. A febrile day was defined as any 24-hour period during which the patient

had a temperature$100.5°F or 38.1°C. Hypoxia was defined as an

oxygen saturation of #95% by pulse oximetry (while breathing

room air). Tachypnea was defined as a respiratory rate (breaths/ minute) greater than the normal range for the respective age groups. For repeat CXRs: resolution was defined as a completely normal CXR with no evidence of abnormality; partial resolution was defined as improvement of the CXR but with persistence of an abnormality; no resolution was defined as no change in or a worsening of the abnormality. Clinical response was defined as good if the patient had improvement or resolution of his/her signs and symptoms during antimicrobial therapy.

Determination of the serotype and minimal inhibitory concen-tration (MIC) for penicillin and ceftriaxone of each isolate was performed in a central laboratory to which all isolates were sent. Serotyping/serogrouping was performed by quellung reaction, using specific capsular antisera (Statens Seruminstitut, Copenha-gen, Denmark; Daco, Inc, Carpinteria, CA). Determination of MIC

was done by standard microbroth dilution.7Guidelines set forth

by the National Committee for Clinical Laboratory Standards were used for interpretation of MICs. Susceptibility to penicillin

was defined as a MIC#0.06mg/mL, intermediate susceptibility to

penicillin as a MIC of 0.1 to 1.0mg/mL, and resistance to penicillin

as a MIC$2.0mg/mL. Susceptibility to ceftriaxone was defined as

a MIC#0.5mg/mL, with intermediate susceptibility defined as a

MIC51.0mg/mL, and resistance defined as an MIC$2.0mg/

mL.8 Isolates that are intermediate or resistant are considered

nonsusceptible to penicillin or ceftriaxone.

Outcome variables were analyzed byx2, Fisher’s exact test, and

Wilcoxon ranked sum test for nonparametric data.

RESULTS Clinical Characteristics of the Patients

There were 257 episodes of pneumococcal pneu-monia that occurred in 254 patients during the 3-year period from September 1, 1993 to August 31, 1996. The patients ranged in age from 0.07 to 311 months (mean, 40.6 months; median, 21.8 months). Fifty-six percent of the patients were male; 45% were African-American, 41% were Caucasian, 10% were Hispanic, and 4% were other races. Ninety-two (36%) of the patients had underlying conditions that included central nervous system disorders (n 5 17), genetic problems (n 5 12), hematologic conditions (n 5 9), prematurity (n58), chronic pulmonary disease (n5

8), human immunodeficiency virus (n 5 7), cardiac problems (n 5 6), immunologic disorders (n 5 6), and other miscellaneous problems. Ten (11%) of these patients had received one or more doses of 23-valent pneumococcal vaccine before their infec-tion. Twenty-seven percent of the patients had re-ceived a course of antibiotics within the 30 days before developing pneumococcal pneumonia.

The most common presenting signs, symptoms, and findings on physical examination are shown in Fig 1. Eighteen percent of the patients had symptoms compatible with a preceding viral upper respiratory tract infection (median duration, 7 days; range, 1–21 days). The mean duration of fever before diagnosis was 3.1 days, (median, 2 days; range, 0.04 –28 days). The median peripheral WBC count at the time of presentation was 19.53103/mm3(range, 0.1– 89.83 103 /mm3). Sixty-nine percent of the patients had peripheral WBC counts $20 3 103/mm3 and 31% had counts$303103/mm3. Blood culture was pos-itive for S pneumoniae in 93% of the patients; 7% of the patients had a positive pleural fluid culture alone. Seventy-four percent (n5189) of the patients were hospitalized for treatment of their pneumonia.

Susceptibility and Serotypes/Serogroups of the Isolates Of the 257 isolates, 22 (8%) were intermediate to penicillin and 14 (6%) were resistant to penicillin; 7 (3%) were intermediate to ceftriaxone and 5 (2%) were resistant to ceftriaxone. The most commonly recovered serotypes/serogroups, in their relative or-der of prevalence were 14 (34.4%), 6 (17.2%), 19 (14.4%), 9 (7.2%), 1 (7.2%), 23 (4.8%), 4 (4.8%), and 3 (2.4%).

Inpatient Versus Outpatient Treatment

Table 1 is a comparison of selected clinical and radiographic characteristics of patients who were hospitalized for treatment of their pneumonia and those who were treated as ambulatory patients. Chil-dren who were hospitalized were significantly more likely to have an underlying illness (P,.001), mul-tiple lobe involvement (P , .001), and a pleural effusion (P,.001).

(3)

fluid lactate dehydrogenase levels ranged from 670 to 63 522 IU/L (n5 18). Urokinase was used as an adjunctive measure in 5 (10%) of the patients with chest tubes; 2 of these patients subsequently had a decortication procedure performed.

Twenty-seven (14.3%) of the hospitalized patients (10.6% of all the patients) underwent a more defini-tive decortication drainage procedure. The median age of these patients was 61.5 months (range, 4 –215 months; mean, 75 months). One-third of these

pa-tients had an underlying illness. Ninety-three per-cent of these patients were febrile before diagnosis of pneumonia with pleural effusion, with a median du-ration of fever of 6 days (range, 1–20 days; mean, 6.5 days). Decreased breath sounds over the affected area and hypoxia were the most common physical examination findings occurring in 89% of these pa-tients. CXRs showed that 85% had a consolidative pattern with 74% having $2 lobes involved. The drainage procedure was performed anytime between the day of admission to 11 days (mean, 4 days; median, 3 days) after hospital admission. The pleural fluid parameters of these patients included pleural fluid WBC counts ranging from 850 to 275 000/mm3 (n 5 17) with the percent polymorphonuclear cells ranging from 80 to 99. Twelve of 16 specimens (75%) had a glucose value of,20 mg/dL and protein val-ues ranged from 3.1 to 5.1 g/dL (n517). There were no significant differences for pleural fluid values (percent glucose concentration,20 mg/dL, percent protein concentration .4.0 g/dL, or percent WBC count .10 000/mm3) between the patients treated with chest tube drainage alone versus those who underwent thoracotomy/decortication. Eighty-five percent of these patients had a positive Gram stain and/or culture or latex agglutination antigen test. After the decortication procedure, the mean time to defervescence was 7 days (range, 1–18 days; median, 6 days), the mean duration of O2requirement was 5 days (range, 1–39 days; median, 8.8 days), and the mean duration of hospitalization was 13 days (range,

Fig 1. The most common clinical signs and symptoms and physical examination findings in 254 pediatric patients with pneumococcal pneumonia.

TABLE 1. Clinical and Radiographic Characteristics of Chil-dren With Pneumococcal Pneumonia Managed as Inpatients Ver-sus Outpatients

Characteristic Inpatients (n5189)

Outpatient (n565) Age, mo 28.5 (0.067–311)‡ 17.5 (4–92.5)‡ Underlying disease 84 (44%)§ 8 (13%) Penicillin nonsusceptible

isolates†

27 (14%) 8 (13%)

Peripheral white blood cell count3103/mm3

20.31 (0.1–89.8)‡ 21.45 (6.0–48.5)‡

Chest radiograph findings

Consolidation 102 (54%) 27 (41%)

$2 Lobes 89 (47%)\ 11 (17%) Effusion 72 (38%)¶ 1 (2%) * Does not include patients with asthma or recurrent otitis media. † For patient with two separate episodes of pneumonia each with nonsusceptible isolate, only one isolate counted in this Table. ‡ Median (range).

§P5 ,.001.

(4)

7–176 days; median 23.5 days). Eighty-five percent of these patients had partial resolution of their pneu-monic process with the remainder having complete resolution on follow-up CXR performed from 5 to 227 days after the diagnosis of pneumonia.

Penicillin-susceptible Versus Nonsusceptible Isolates Comparisons of clinical and radiographic charac-teristics of those patients whose pneumococcal iso-lates were nonsusceptible to penicillin versus those patients with penicillin-susceptible isolates are shown in Table 2. There were no significant differ-ences for duration of fever, O2requirement, periph-eral WBC count, or CXR findings between the two groups. Furthermore, a comparison of the clinical and radiographic characteristics of only inpatients who had isolates ofS pneumoniae that were suscep-tible to penicillin versus those with isolates of S pneumoniae that were not susceptible to penicillin demonstrated no differences between the two groups.

To determine if the presence of an underlying illness and the susceptibility of the isolate made a difference in the clinical course of the pneumonia in hospitalized patients, selected clinical characteristics of those patients with an underlying illness were compared based on the penicillin susceptibility of their isolate. No differences were demonstrated with regard to age, peripheral WBC count, defervescence, duration of O2 requirement, CXR findings, or need for chest tube. Among patients with an underlying illness, those with pneumococcal isolates that were nonsusceptible to penicillin were hospitalized for a median duration of 12.5 days compared with 7 days in those patients with susceptible isolates,P5.04.

Antimicrobial Therapy

The antimicrobial regimens of the patients were highly variable. However, for those patients treated as outpatients, 80% received a dose of a parenteral second or third generation cephalosporin followed by a course of an oral antimicrobial agent. Seventeen percent of the patients were treated with a course of an oral b-lactam antibiotic alone (penicillins and cephalosporins) and the remaining 3% received a course of a non-b-lactam oral antimicrobial agent.

Forty-eight percent of the inpatients were treated with a course of a second or third generation

paren-teral cephalosporin followed by a course of an oral antimicrobial agent. Twenty percent of the patients received a parenteral cephalosporin in combination with intravenous penicillin or another intravenous antibiotic, 16% received a parenteral cephalosporin in combination with intravenous vancomycin (medi-an duration, 3 days; me(medi-an, 4.7 days; r(medi-ange, 0.33–25 days), and 2% of the patients received intravenous rifampin in combination with other antimicrobial agents. The remaining 14% of inpatients were treated with other intravenous antibiotics alone or in com-bination with an oral agent or intravenous penicillin, or with monotherapy consisting of a parenteral ceph-alosporin, or intravenous vancomycin.

Patients With Penicillin Resistant Isolates

Table 3 illustrates selected characteristics of the 16 patients who had pneumococcal isolates that were resistant to penicillin and/or ceftriaxone; only 3 pa-tients received vancomycin. There were no differ-ences found with regard to age, peripheral WBC count, clinical or radiographic findings, antimicro-bial regimen, or outcome between these patients and those patients with susceptible isolates.

Follow-up CXRs

Follow-up CXRs were performed in 121 (48%) of the 254 patients, ranging from 1 to 274 days after the diagnosis of pneumonia was made. Of these patients, 26% had total resolution and 59% had partial reso-lution. The susceptibility of the isolate was not re-lated to whether or not resolution occurred.

Response to Therapy

Of the 254 patients, 248 (97.6%) had a good re-sponse to therapy and recovered from their pneumo-nia. The characteristics of the 6 patients (2.4%) who died are shown in Table 4. All of these patients had underlying illnesses, 5 were treated with vancomy-cin plus a parenteral cephalosporin, however, only 1 of these patients had a penicillin-resistant isolate (MIC52.0mg/mL). Only 1 of the deaths (patient 2) was felt to be related to the pneumococcal infection.

DISCUSSION Clinical Presentation

Most of the information pertaining to the clinical presentation and treatment of pneumococcal

pneu-TABLE 2. Clinical and Radiographic Characteristics of Children With Pneumococcal Pneumonia Attributable to Susceptible Versus

Nonsusceptible Isolates

Characteristics Penicillia-Susceptible

(n5218)

Penicillin-Nonsusceptible

(n536)

Age, mo 25 (0.067–311)* 21.5 (0.5–284)*

Underlying disease 74 (34%) 17 (47%)

Hospitalization n5161 n528

Defervescence, days 2 (1–25)* 2 (1–16)*

Duration of O2req, days 4 (0.33–39)* 4.5 (1–19)*

Hospitalization duration, days 6 (1–176)* 5.5 (1–45)*

White blood cell count3103/mm3 21.5 (0.1–89.8)* 19.2 (3.6–52.1)*

Chest radiograph findings

Consolidation 111 (51%) 18 (50%)

$2 Lobes 86 (40%) 14 (39%)

Effusion 66 (30%) 7 (19%)

(5)

monia comes from case series and reports in adult patients.4,5,9 –11However, only one recently published study in adults has addressed the outcome of pneu-mococcal pneumonia based on the antibiotic suscep-tibility of the isolates.12 Pallares et al12 conducted a 10-year, prospective study of 504 adults with culture-proven pneumococcal pneumonia to examine the effect of penicillin and cephalosporin resistance on mortality. Of the 504 patients, 145 (29%) had strains ofS pneumoniaethat were nonsusceptible to

penicil-lin (62 with MIC $2.0 mg/mL) and 31 (6%) had

strains that were nonsusceptible to cephalosporins. There were no significant differences in mortality among adult patients with pneumococcal pneumo-nia based on the susceptibility of their isolate to penicillin or cephalosporins.

Data describing the clinical presentation and treat-ment of pneumococcal pneumonia in the pediatric population with regard to patients with penicillin nonsusceptible isolates are limited. Friedland and colleagues6 examined selected clinical and radio-graphic characteristics in 78 South African children who were hospitalized with pneumococcal pneumo-nia. Twenty-five of these patients had isolates of S pneumoniaethat were intermediate to penicillin; none of the isolates were resistant to penicillin (MIC$2.0

mg/mL). The only significant differences found be-tween the two groups were a greater number of children who were human immunodeficiency virus-positive or who had received antibiotic therapy in the month before hospital admission in the group whose isolates of S pneumoniaewere nonsusceptible to penicillin.

Hardie et al13compared the clinical characteristics and outcome of children with complicated para-pneumonic effusions caused by S pneumoniae non-susceptible to penicillin (n56) to those cases caused by isolates susceptible to penicillin (n 5 17). The results of the study showed that complicated parap-neumonic effusions caused by penicillin nonsuscep-tibleS pneumoniaewere associated with younger age

and higher rates of bacteremia. However, no signif-icant differences in outcome measures were found between patients infected with penicillin-susceptible versus nonsusceptible organisms.

In our group of patients the most common present-ing signs and symptoms included fever, a nonpro-ductive cough, and malaise/lethargy. The most

com-mon findings on physical examination were

decreased breath sounds over the affected area and crackles/rales. When tested, hypoxia (O2saturation

#95%) occurred in almost half of the patients. Com-pared with adult patients (20%– 45%), the overall mortality rate for children with bacteremic pneumo-coccal pneumonia is low. Six patients (2.4%) died but only 1 of the deaths was attributable to the pneumo-coccal infection.

Pleural Effusion/Empyema

In adults with pneumococcal pneumonia, pleural effusions may occur in up to 57% of the cases.14,15 Most pleural effusions will resolve spontaneously without the need for further intervention. However, because of the interplay of a number of host and microbial factors, pleural effusions may progress to become empyemas (a collection of purulent material in the pleural space). Pleural empyema is the most common complication of bacterial pneumonia. Ex-amination of pleural fluid parameters helps to deter-mine the presence of an empyema and the need for a drainage procedure. The occurrence of pleural em-pyema in pneumococcal pneumonia has an inci-dence ranging from 2% to 8%.14,16Thirty-five of our patients, or 13.8%, had one or more pleural fluid parameters indicative of an empyema.

The most appropriate treatment of pleural empy-ema in children is controversial. Most children with empyemas can be adequately treated with antibiotics and repeated pleural fluid aspirations or chest tube drainage.17,18 A more definitive surgical drainage procedure may be required in patients who continue to have respiratory distress, fever, persistent

periph-TABLE 3. Selected Characteristics of Children With Pneumococcal Pneumonia Attributable to Penicillin and/or Cephalosporin

Resistant Isolates Age (Months)

Underlying Disease MIC (PCN/CTX)

mg/mL

Therapy (Days)

21 Microcephaly 2/1 Cefuroxime (5), vancomycin (16), rifampin (14)

39 SCID, s/p BMT 2/0.5 Timentin (6), gentamicin (6), cefotaxime (1), clindamycin (4)

0.5 Osteogenesis imperfecta 2/1 Cefuroxime (3), amoxicillin/clavulanic acid (14)

157 Hodgkin’s disease 2/1 Cefuroxime (10)

9 Static encephalopathy 2/0.5 Vancomycin (1), cefotaxime (6)

31 Cerebral palsy, former 27-week

premature infant

4/0.5 Cefotaxime (2), cefuroxime (5), vancomycin (10)

33* None 4/1 Amoxicillin/clavulanic acid (10)

6 None 4/1 Cefotaxime (10)

22* None 2/0.5 Ceftriaxone (1 dose), amoxicillin (1), cefpodoxime (9)

31 None 2/0.5 Cefuroxime (1 dose), cefotaxime (2), cefixime (9)

11.5* None 2/1 Amoxicillin/clavulanic acid (10)

173.5 Thoracic anomaly 1/2 Cefotaxime (11), gentamicin (2)

49 HIV 2/2 Cefuroxime (4), cefpodoxime (10)

43 None 2/2 Ceftriaxone (5), penicillin (10), rifampin (2)

4* None 4/8 Cefuroxime (1 dose), amoxicillin (14)

12 None 0.12/2 Cefuroxime (3), amoxicillin/clavulanic acid (8)

Abbreviations: MIC (PCN/CTX), minimal inhibitory concentration (penicillin/ceftriaxone); SCID, severe combined immunodeficiency; s/p BMT, status post bone marrow transplant; HIV, human immunodeficiency virus; timentin, ticarcillin/clavulanic acid.

(6)

eral leukocytosis, and worsening CXR despite the use of appropriate antibiotics and drainage. Al-though open thoracotomy with lung decortication remains controversial in the treatment of empyemas in children, studies have shown the procedure to be low risk and effective in providing rapid clinical improvement in cases of refractory pleural empy-ema.19 –22 Unfortunately, there have been no con-trolled prospective trials in children comparing the outcome of different treatment strategies for the treatment of empyema. Thoracoscopy with adhesi-olysis and pleural debridement23and mini-thoracot-omy24are two alternatives to open thoracotomy that also have been used successfully in the treatment of children with refractory empyema. In our series of patients, those who underwent mini-thoracotomy or thoracoscopy (n5 9) for drainage of pleural empy-emas did as well as those patients who underwent a more invasive procedure (n5 18).

Antimicrobial Therapy

The optimal antimicrobial regimen for the treat-ment of infections caused by isolates ofS pneumoniae

that are nonsusceptible to penicillin, especially those with a high level of resistance (MIC $2.0 mg/mL), has not been established. Penicillin therapy is inad-equate for the treatment of meningitis attributable to

S pneumoniae that is resistant to penicillin.25 How-ever, for penicillin-resistant pneumococcal infections outside of the central nervous system, the data are not clear. Although most experts recognize that pen-icillin therapy may be effective for infections caused by strains with intermediate susceptibility to penicil-lin,26 –28 there are little or no data pertaining to iso-lates resistant to penicillin. The achievable peak se-rum concentrations for standard doses of oral

b-lactam agents (eg, amoxicillin with or without cla-vulanic acid or cephalosporins, etc) may be 3 to 7 times greater than the MIC of a resistant strain.29,30 Although some studies suggest that infections attrib-utable to isolates ofS pneumoniaethat are intermedi-ate as well as some that are resistant to penicillin may respond adequately to penicillin and otherb-lactam agents,6,10,28,31 therapy with the extended-spectrum cephalosporins and non-b-lactam agents (vancomy-cin) is usually recommended for patients with iso-lates of pneumococci that have a high level of resis-tance to penicillin or those who are critically ill. Therapeutic changes have usually been based on the susceptibility of the isolate and not on the clinical response of the patient.

Among our patients with resistant isolates, 1 pa-tient whose isolate had an MIC to penicillin of 4

mg/mL was treated as an outpatient with a 10-day course of amoxicillin/clavulanic acid. Another pa-tient whose isolate had an MIC to penicillin of 4

mg/mL and an MIC to ceftriaxone of 8 mg/mL was treated as an outpatient with a single intramuscular dose of cefuroxime of 40 mg/kg followed by a 14-day course of amoxicillin. Both patients recovered from their pneumonias uneventfully despite having isolates with susceptibilities that were in the resistant range. All of the other patients with highly-resistant isolates received at least one dose of an

(7)

extended spectrum b-lactam agent. Two patients also received vancomycin in combination with an advanced generation cephalosporin and 1 patient each was treated with rifampin and vancomycin and rifampin in combination with an advanced genera-tion b-lactam agent. At recommended doses, the peak serum concentrations of these agents can range from 100 to 200 mg/mL, therefore providing blood and tissue concentrations that may exceed the MIC of a resistant isolate by 100-fold.32–34Scaglione and col-leagues35 examined the distribution pharmacokinet-ics of cefotaxime and ceftriaxone into serum and pleural exudates of adults who were given a single intravenous 1-gram dose. Very high levels of the free drug are achieved both in serum and in pleural exudate.

The best treatment regimen for pneumococcal pneumonia is still unknown. Clinical outcome after treatment of pneumococcal pneumonia in children needs further investigation. Our data suggests that in otherwise normal patients with pneumonia attribut-able to penicillin-resistant pneumococcal isolates, therapy with standard b-lactam agents is effective; however, the issue of optimal therapy will have to be continually reassessed as the frequency and intensity of S pneumoniae resistance to various antimicrobial agents continues to increase.

ACKNOWLEDGMENTS

This study was supported in part by a grant from Roche Lab-oratories.

We thank Constance Rothermel, PhD, for her support. We also acknowledge the help of the following individuals: Timothy Pos-tula; Tracye Paris, RN; Susana Aragon, RN; Michelene Ortenzo; Nancy C. Tucker, RN; and Kathyann Marsh, MSN.

REFERENCES

1. Williams WW, Hickson MA, Kane MA, et al. Immunization policies and vaccine coverage among adults.Ann Intern Med. 1988;108:616 – 625 2. McCracken GH Jr. Emergence of resistantStreptococcus pneumoniae: a

problem in pediatrics.Pediatr Infect Dis J.1995;14:424 – 428

3. Appelbaum PC. Antimicrobial resistance inStreptococcus pneumoniae: an overview.Clin Infect Dis.1992;15:77– 83

4. Coonrod JD. Pneumococcal pneumonia.Semin Respir Infect.1989;4:4 –11 5. Musher DM. Pneumococcal pneumonia including diagnosis and ther-apy of infections caused by penicillin-resistant strains.Infect Dis Clin North Am.1991;5:509 –521

6. Friedland IR. Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease. Pe-diatr Infect Dis J.1995;14:885– 890

7. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing. Sixth informational sup-plement M1150 –56. Wayne, PA: National Committee for Clinical Lab-oratory Standards; 1995

8. Minimum Inhibitory Concentration (MIC) Interpretive Standards (mg/ mL) forStreptococcus spp. Table 2C. M100-S7. NCCLS Vol 17. No 2. 1997 9. Marfin AA, Sporrer J, Moore PS, et al. Risk factors for adverse outcome

in persons with pneumococcal pneumonia.Chest. 1995;107:457– 462 10. Pallares R, Gudiol F, Linares J, et al. Risk factors and response to

antibiotic therapy in adults with bacteremic pneumonia caused by

penicillin-resistant pneumococci.N Engl J Med.1987;317:18 –22 11. Esposito AL. Community-acquired bacteremic pneumococcal

pneumo-nia.Arch Intern Med.1984;144:945–948

12. Pallares R, Linares J, Vadillo M, et al. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain.N Engl J Med.1995;333:474 – 480

13. Hardie WD, Roberts NE, Reising SF, et al. Complicated parapneumonic effusions in children caused by penicillin-nonsusceptibleStreptococcus pneumoniae.Pediatrics.1998;101:388 –392

14. Light RW, Girard WM, Jenkinson SG, George RB. Parapneumonic ef-fusions.Am J Med.1980;69:507–512

15. Taryle DA, Potts DE, Sahn SA. The incidence and clinical correlates of parapneumonic effusions in pneumococcal pneumonia.Chest.1978;74: 170 –173

16. Bryant RE, Salmon CJ. Pleural empyema.Clin Infect Dis.1996;22:747–764 17. McLaughlin FJ, Goldmann DA, Rosenbaum DM, et al. Empyema in children: clinical course and long-term follow up.Pediatrics.1984;73: 587–593

18. Murphy D, Lockhart CH, Todd JK. Pneumococcal empyema.Am J Dis Child.1980;134:659 – 662

19. Hoff SJ, Neblett WW, Edwards KM, et al. Parapneumonic empyema in children: decortication hastens recovery in patients with severe pleural infections.Pediatr Infect Dis J.1991;10:194 –199

20. Gustafson RA, Murray GF, Warden HE, et al. Role of lung decortication in symptomatic empyemas in children.Ann Thorac Surg. 1990;49: 940 –947

21. Kosloske AM, Cartwright KC. The controversial role of decortication in the management of pediatric empyema.J Thorac Cardiovasc Surg.1988; 96:166 –170

22. Foglia RP, Randolph J. Current indications for decortication in the treatment of empyema in children.J Pediatr Surg.1987;22:28 –33 23. Kern JA, Rodgers BM. Thoracoscopy in the management of empyema in

children.J Pediatr Surg.1993;28:1128 –1132

24. Raffensperger JG, Luck SR, Shkolnik A, et al. Mini-thoracotomy and chest tube insertion for children with empyema.J Thorac Cardiovasc Surg.1982;84:497–504

25. Ward J. Antibiotic-resistantStreptococcus pneumoniae: clinical and epi-demiologic aspects.Rev Infect Dis.1981;3:254 –265

26. Friedland IR, McCracken GH Jr. Management of infections caused by antibiotic-resistantStreptococcus pneumoniae. N Engl J Med. 1994;331: 377–382

27. Feldman C, Kallenbach JM, Miller SD, et al. Community-acquired pneu-monia due to penicillin-resistant pneumococci.N Engl J Med.1985;313: 615– 617

28. American Academy of Pediatrics, Committee on Infectious Diseases. Therapy for children with invasive pneumococcal infections.Pediatrics.

1997;99:289 –299

29. Ginsburg CM, McCracken GH Jr, Nelson JD. Pharmacology of oral antibiotics used for treatment of otitis media and tonsillopharyngitis in infants and children.Ann Otol Rhinol Laryngol. 1981;84:37– 43 30. Krause PJ, Owens NJ, Nightingale CH. Penetration of amoxicillin,

ce-faclor, erythromycin-sulfisoxazole, and trimethoprim-sulfamathoxazole into the middle ear fluid of patients with chronic serous otitis media.

J Infect Dis.1982;145:815– 821

31. Tan TQ, Mason EO, Kaplan SL. Systemic infections due toStreptococcus pneumoniae relatively resistant to penicillin in a children’s hospital: clinical management and outcome.Pediatrics.1992;90:928 –933 32. Kaplan SL. Serious pediatric infections.Am J Med.1990;88:18S–24S 33. Steele RW, Bradsher RW. Ceftriaxone for the treatment of serious

in-fections.Am J Dis Child.1983;137:1044 –1047

34. Trang JM, Jacobs RF, Kearns GL, et al. Cefotaxime and desacetylcefo-taxime pharmacokinetics in infants and children with meningitis. An-timicrob Agents Chemother.1985;28:791–795

(8)

DOI: 10.1542/peds.102.6.1369

1998;102;1369

Pediatrics

Kim and Sheldon L. Kaplan

Schutze, John S. Bradley, Moshe Arditi, Laurence B. Givner, Ram Yogev, Kwang Sik

Tina Q. Tan, Edward O. Mason, Jr, William J. Barson, Ellen R. Wald, Gordon E.

Streptococcus pneumoniae

to Penicillin-susceptible and Penicillin-nonsusceptible

Clinical Characteristics and Outcome of Children With Pneumonia Attributable

Services

Updated Information &

http://pediatrics.aappublications.org/content/102/6/1369

including high resolution figures, can be found at:

References

http://pediatrics.aappublications.org/content/102/6/1369#BIBL

This article cites 33 articles, 5 of which you can access for free at:

Subspecialty Collections

http://www.aappublications.org/cgi/collection/pulmonology_sub

Pulmonology

http://www.aappublications.org/cgi/collection/therapeutics_sub

Therapeutics

http://www.aappublications.org/cgi/collection/pharmacology_sub

Pharmacology

b

http://www.aappublications.org/cgi/collection/infectious_diseases_su

Infectious Disease

http://www.aappublications.org/cgi/collection/hospital_medicine_sub

Hospital Medicine following collection(s):

This article, along with others on similar topics, appears in the

Permissions & Licensing

http://www.aappublications.org/site/misc/Permissions.xhtml

in its entirety can be found online at:

Information about reproducing this article in parts (figures, tables) or

Reprints

http://www.aappublications.org/site/misc/reprints.xhtml

(9)

DOI: 10.1542/peds.102.6.1369

1998;102;1369

Pediatrics

Kim and Sheldon L. Kaplan

Schutze, John S. Bradley, Moshe Arditi, Laurence B. Givner, Ram Yogev, Kwang Sik

Tina Q. Tan, Edward O. Mason, Jr, William J. Barson, Ellen R. Wald, Gordon E.

Streptococcus pneumoniae

to Penicillin-susceptible and Penicillin-nonsusceptible

Clinical Characteristics and Outcome of Children With Pneumonia Attributable

http://pediatrics.aappublications.org/content/102/6/1369

located on the World Wide Web at:

The online version of this article, along with updated information and services, is

by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Figure

TABLE 1.Clinical and Radiographic Characteristics of Chil-dren With Pneumococcal Pneumonia Managed as Inpatients Ver-sus Outpatients
TABLE 2.Clinical and Radiographic Characteristics of Children With Pneumococcal Pneumonia Attributable to Susceptible VersusNonsusceptible Isolates
TABLE 3.Selected Characteristics of Children With Pneumococcal Pneumonia Attributable to Penicillin and/or CephalosporinResistant Isolates

References

Related documents

Due to high reliability, high data rate, performance, stability over changing temperature conditions, good compatibility with optical fibers, low driving voltage, low drift in

– so-called “intuitive” processes of risk perception and evaluation performed by individuals and groups for their everyday decisions about the acceptability of risks; –

This instability in politics has caused some serious social disruptions in the country. Ethnic, religious and political conflicts have given a very tough time to the

The aim of this study was to evaluate influence of climatic conditions represented by daily air temperature and relative air humidity on indicators of Holstein cows’ milk quality

Steatitisation of the Vempalle dolomites is more common in the present area close to the contact of the dolerite, preferably the upper contact. The steatite occurs in the form

In 12-20 a few higher order equations are considered for integral solutions.. Applying the process parallel to that of patterns I to III, other choices of essential

Table: 2: Frequency and percentage distribution of post test scores of Joint and muscular discomforts among menopausal women in experimental group and control group after