INFECTIOUS DISEASES
Hemophilus Influenzae Septic Arthritis in Infants and Children Mark Harlow, M.D., Stanley M. K. Chung, M.D., Stanley A. Plotkin, M.D.*
N
ELSONl,2 has established the importance of H. influenzae type B as a cause of septic arthritis in infants and young children. In his series, it was responsible for 33 per cent of the cases in which the patients were under two years of age and was by far the most frequent pathogen identified by culture. Despite the fact that Nelson's first publication was over seven years ago, and other reports have since appeared.v" the frequency of H. influenzae in septic arthritis seems not to be generally recognized, perhaps because clinical descriptions of cases have not been emphasized in the pediatric literature. Therefore, we here describe seven patients in some detail in order to define the initial symptoms, evolution, treatment, and outcome of the disease. Method for Typing of Hemophilus Influenzae
Colonies of the isolated organisms grown on Levinthal agar for 24 hours or less were emulsified in saline and placed on a slide
* Division of Pediatric Orthopedics and Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pa. 19104.
1146
together with a drop of Hyland Type B antiserum. Antiserum to one of the other capsular types was always tested as a negative control. If macroscopic agglutination did not occur with the two antisera initially employed, the test was repeated with antisera to all six capsular types. Results
Records at the Children's Hospital of Philadelphia over the past 12 years have revealed seven cases with the diagnosis "septic arthritis secondary to H. influenzae" (Table 1). The children ranged in age from seven months to three and one-half years. A total of nine joints were involved, with two joints in each of two patients. The joints infected included three elbows, three knees, two ankles, and one tarsometatarsal joint. The patients' illnesses began with four to six days of fever and symptoms referable to the nasopharynx, ears, or involved joint. A history of trauma to the joint was obtained in only two of the seven cases, whereas all of the cases had upper respiratory tract symptoms, often with frank otitis. Physical examination revealed nasopharyngeal or middle ear inflammation and signs Vol. 14 No. 12
CLINICAL PEDIATRICS
HEMOPHILUS SEPTIC ARTHRITIS
TABLE
1. Summary
ofSeven
Patients with H. Influenzae Arthritis
Age
Year
Clinical
Culture
CBC
Antibiotics
9 mo. No 7.7 kg
1971
3d hx. of swelling & pain right elbow manipulated 2 times elsewhere for pulled elbow PE: swollen red elbow ~ ROM pharyngitis
blood & joint +
Hgb 7.2 WBC 23.2 62 seg. 4 bands 32L 2M
naf 800 mg. d 1-2 ampi 2.4 gms IV d 3-20 ampi 1.0 gm po d 21-22
3 yr. Bo
1973
5d hx. otitis & 3d hx, limited use right leg right arm PE: otitis media-swelling erythema tender ~ ROM right elbow & left ankle
+ nasopharynx
Hgb 9.7 WBC 21.2 63 seg. 5 bands 30L5M
ampi 400 mg/kg/d LV. d 1-21
15 mo. Wo
1973
4d hx. swelling right ft., URI PE: swollen erythematous dorsum of right ft. tender 10° of ankle motion
+ dorsum foot
Hgb 16.4 WBC 16.1 40P 3 seg. 40L 3M 10E 1B
naf + genta d-I-2 ampi IV d 3-7
2 yr. 4 mo. Bo 12 kg
1973
10d PTA treated for URI rd hx. pain left knee PE: swollen tender left knee ~ ROM
+ knee
Hgb 8.7 WBC 26.5 55P 4 bands 36L 5M
naf 200 mg/kg d 1-3 ampi 300 mg/kg d 4-26
14 mo. No 12.7 kg
1962
24 hx. increasing pain with swelling left ankle PE: otitis media swollen left ankle ~ ROM
joint blood nasopharynx +
Hgb 8.3 WBC 10.8 48P 46L 2B 3M IE
PCN. 1.2 x \06 u 1M daily chloro1 gm daily for 2 wks.
3\12 yr.
1962
6d. hx. URI irritability swelling pain left knee left elbow
NP blood CSF + jointn.g.
Hgb 11.0 WBC 18.8 61P 29L 6B
chloro- LV. daily for 3 days, then 1.5 gm. po/daily
17 mo. No 11.4 kg
1966
fever 3 d. coryza 1 d. limp right knee swollen & tender ROM minus \00 to 90°
+ joint fluid
Hgb 11.9 WBC 17.4 66 seg. 10 bands 9 met 15L
PC N° 3.6 x \06 U 1M daily chloro2.0 gm. 1M daily 4 days then chloro 1 gm. + PCN 1 gm. P.O. daily
Wo 15.4 kg
Key: ROM-range of motion LOMFROM-full range of motion
N-normal temperature PCN - penicillin amp-ampicillin
of infection in the involved joints, which were tender, erythematous, swollen, and had a decreased range of motion. In all cases, the WBC was elevated with a left shift. The sedimentation rate was also elevated when obtained. CLINICAL PEDIATRICS
blood, right elbow left ankle
December 1975
Cultures of the joint fluid were positive for H. injiuenzae type B in five of seven patients; and the sixth had H. injiuenzae type E. Nospharyngeal cultures were positive for H. influenzae type B when done (three out of three). Bacteremia was present in four of
1147
HARLOW, CHUNG, AND PLOTKIN
TABLE 1. Summary Fever Profile
Joint
ofSeven
Patients with the H lnfluenzae Arthritis (Continued)
Other Treatment
X-ray
Follow-up
102.2°F. N2Y2 days
purulent fluid
day I-incision and drainage
soft tissue swelling elbow
7 wks LOM (50%)
103°--+N at 11th day
purulent fluid
day 1-4 tapknee day I-elbow tap no fluid day 10incision & drainage of left ankle
both knee & ankle soft tissue swelling; then 10 days later lytic lesion left distal fibula
6 wks. elbow good ROM ankle LOM (30%)
102°--+N 3 days
3 cc. purulent fluid
day I-tap day 3-incision & drainage of foot
diffuse soft tissue swelling dorsum foot
good ROM 4 wks.
102° N-8 days
20 cc. purulent fluid
day 1-5 daily tap day 6-incision & drainage of knee
soft tissue swelling knee
good ROM 6 weeks
102°--+N 8th day
3 cc. purulent fluid gram stain g+
l st day-tap 3 cc. purulent fluid 3rd day-2 cc. purulent fluid intra-articular 1 mill PCN instilled on 4th day-2 cc. 5th day-2 cc. 6th day-dry tap
Ist day soft tissue swelling
6 yr. persistent LOM and pain
105°--+ N on 4th day
5 cc. purulent fluid knee
1st day-tap 15 cc-. purulent fluid 8th day-tap knee 15 cc. serupurulent fluid. chloromycetin 15 mg intra-articular given
knee + elbow soft tissue swelling
4 wks. 0-145° ROM persistent synovial thickening
105°--+N in 5 days
purulent fluid
1st day-tap knee 6 cc. pus 2nd day - tap knee 6 cc. pus. PCN 1 million u intraarticular 3rd day -tap knee 6 cc. pus. PCN repeated
knee-soft tissue swelling
2 mos. spica at 4 yrs. FROM with no pain
gent-gentamicin chloro-chloramphenicol
n.g.-no growth naf- nafcillin
four patients tested. All seven had at least one positive culture for H. irifluenzae. Roentgenograms uniformly revealed soft tissue swelling with occasional evidence of joint effusion, but no destruction of bone. Before 1967, antibiotics used in treatment were penicillin and chloramphenicol par-
1148
enterally and intra-articularly. Since that time, intravenous ampicillin has been used for approximately three weeks. Ampicillin was not given intra-articularly. Three cases required surgical intervention because of recurrent effusions, continued pain, and fever after two days of treatment with antiVol. 14 No. 12
CLINICAL PEDIATRICS
HEMOPHILUS SEPTIC ARTHRITIS
biotics. Lysis of fever occurred within two days after surgical decompression. Long-term follow-up was accomplished on four patients, three of whom completely recovered. One patient's ankle joint was completely destroyed. The other three patients were lost to follow-up. Discussion
The optimal treatment for septic joints in children begins with a rapid determination of bacterial etiology by aspiration and proper culture techniques. Whenever a joint is aspirated, the fluid should be evaluated for viscosity and cloudiness and should have a cell count, gram stain for bacteria, culture for mycobacteria and for bacteria including Hemophilus influenwe. Cultivation of H. influenzae requires media containing X and V factors. Therefore, only media such as Levinthal and chocolate agar are suitable, and unless they are employed routinely in culture of septic joints, infection with this organism may be missed. Moreover, although commonly cultures are negative from joint fluid in obvious septic arthritis, if the patient is below two years of age, H. injiuenzae should be strongly suspected. The development of H. injiuenzae arthritis is presumably the result of nasopharyngeal infection leading to bacteremia, during which arthritis, meningitis, cellulitis, or other septic complications may occur. As in the other H. influenzae septic complications, type B is usually the capsular type of the organism involved. We found that commonly an infected joint in a child is assumed to be caused by Staphylococcus aureus and that treatment with an intravenous penicillin such as nafcillin is undertaken. The lack of clinical response should lead one to suspect H. injiuenzae septic arthritis especially in a child less than two years of age. The treatment of septic arthritis in the infant should combine ampicillin with a penicillin active against penicillinaseproducing staphylococci, such as nafcillin,
CLINICAL PEDIATRICS
December 1975
methicillin, or oxacillin. If H. influenzae is isolated from the joint, treatment can then be continued with ampicillin alone for three weeks at a dosage of 150/mg/kg/day in four divided doses, given intravenously or intramuscularly. Joint fluid levels on these parenteral regimens have been shown to be adequate for effective treatment." We do not feel longer therapy with intravenous or oral antibiotics is necessary. If the organism proves to be resistant to ampicillin, chloramphenicol is an excellent alternative. In addition, plaster splints or casts should be used to immobilize the joint for four to six weeks for patient comfort. If the response to one or two joint aspirations is good (in 36 to 48 hours) as determined by rapid decrease of fever, minimal reaccumulation of fluid and good return of painless motion, intravenous ampicillin can be the definitive treatment. If, however, there is slow response or rapid reaccumulation of joint fluid, an incision and drainage of the joint should be immediately done. We believe that an infected hip joint especially should be drained without any attempt at conservative therapy. The blood supply to the femoral head is sensitive to pressure which results in tamponade which in turn will lead to avascular necrosis." References 1. Nelson, J. D., and Koontz, W. C.: Septic arthritis in infants and children: a review of 117 cases. Pediatrics 38: 966, 1966. 2. - - : The bacterial etiology and antibiotic management of septic arthritis in infants and children. Pediatrics 50: 437, 1972. 3. Wall, J. J., ~nd Hunt, D. D.: Acute hematogenous pyarthrosis caused by hemophilus inftuenzae. J. Bone Joint Surg. 50: 1657, 1968. 4. Farrand, R. J.,Johnstone, J. M. S., and Maccabe, A. , F.: Haemophilus osteomyelitis and arthritis. Br. Med. J. 2: 334, 1968. 5. - . - : .Haemophilus inftuenzae type B septicaemia. Br. Med. J. 1: 150, 1969. 6. Nelson, J. D.: Antibiotic concentrations in septic joint effusions. N. Eng!. J. Med. 284: 349, 1971. 7. Soto-Hall, R.: Variation in the intra-articular pressu~e ofthe hip joint in injury and disease. J. Bone Jomt Surg. 46-A: 509, 1965.
1149
Hemophilus Influenzae Septic Arthritis in Infants and Children Mark Harlow, M.D., Stanley M. K. Chung, M.D., Stanley A. Plotkin, M.D.*
N
ELSONl,2 has established the importance of H. influenzae type B as a cause of septic arthritis in infants and young children. In his series, it was responsible for 33 per cent of the cases in which the patients were under two years of age and was by far the most frequent pathogen identified by culture. Despite the fact that Nelson's first publication was over seven years ago, and other reports have since appeared.v" the frequency of H. influenzae in septic arthritis seems not to be generally recognized, perhaps because clinical descriptions of cases have not been emphasized in the pediatric literature. Therefore, we here describe seven patients in some detail in order to define the initial symptoms, evolution, treatment, and outcome of the disease. Method for Typing of Hemophilus Influenzae
Colonies of the isolated organisms grown on Levinthal agar for 24 hours or less were emulsified in saline and placed on a slide
* Division of Pediatric Orthopedics and Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pa. 19104.
1146
together with a drop of Hyland Type B antiserum. Antiserum to one of the other capsular types was always tested as a negative control. If macroscopic agglutination did not occur with the two antisera initially employed, the test was repeated with antisera to all six capsular types. Results
Records at the Children's Hospital of Philadelphia over the past 12 years have revealed seven cases with the diagnosis "septic arthritis secondary to H. influenzae" (Table 1). The children ranged in age from seven months to three and one-half years. A total of nine joints were involved, with two joints in each of two patients. The joints infected included three elbows, three knees, two ankles, and one tarsometatarsal joint. The patients' illnesses began with four to six days of fever and symptoms referable to the nasopharynx, ears, or involved joint. A history of trauma to the joint was obtained in only two of the seven cases, whereas all of the cases had upper respiratory tract symptoms, often with frank otitis. Physical examination revealed nasopharyngeal or middle ear inflammation and signs Vol. 14 No. 12
CLINICAL PEDIATRICS
HEMOPHILUS SEPTIC ARTHRITIS
TABLE
1. Summary
ofSeven
Patients with H. Influenzae Arthritis
Age
Year
Clinical
Culture
CBC
Antibiotics
9 mo. No 7.7 kg
1971
3d hx. of swelling & pain right elbow manipulated 2 times elsewhere for pulled elbow PE: swollen red elbow ~ ROM pharyngitis
blood & joint +
Hgb 7.2 WBC 23.2 62 seg. 4 bands 32L 2M
naf 800 mg. d 1-2 ampi 2.4 gms IV d 3-20 ampi 1.0 gm po d 21-22
3 yr. Bo
1973
5d hx. otitis & 3d hx, limited use right leg right arm PE: otitis media-swelling erythema tender ~ ROM right elbow & left ankle
+ nasopharynx
Hgb 9.7 WBC 21.2 63 seg. 5 bands 30L5M
ampi 400 mg/kg/d LV. d 1-21
15 mo. Wo
1973
4d hx. swelling right ft., URI PE: swollen erythematous dorsum of right ft. tender 10° of ankle motion
+ dorsum foot
Hgb 16.4 WBC 16.1 40P 3 seg. 40L 3M 10E 1B
naf + genta d-I-2 ampi IV d 3-7
2 yr. 4 mo. Bo 12 kg
1973
10d PTA treated for URI rd hx. pain left knee PE: swollen tender left knee ~ ROM
+ knee
Hgb 8.7 WBC 26.5 55P 4 bands 36L 5M
naf 200 mg/kg d 1-3 ampi 300 mg/kg d 4-26
14 mo. No 12.7 kg
1962
24 hx. increasing pain with swelling left ankle PE: otitis media swollen left ankle ~ ROM
joint blood nasopharynx +
Hgb 8.3 WBC 10.8 48P 46L 2B 3M IE
PCN. 1.2 x \06 u 1M daily chloro1 gm daily for 2 wks.
3\12 yr.
1962
6d. hx. URI irritability swelling pain left knee left elbow
NP blood CSF + jointn.g.
Hgb 11.0 WBC 18.8 61P 29L 6B
chloro- LV. daily for 3 days, then 1.5 gm. po/daily
17 mo. No 11.4 kg
1966
fever 3 d. coryza 1 d. limp right knee swollen & tender ROM minus \00 to 90°
+ joint fluid
Hgb 11.9 WBC 17.4 66 seg. 10 bands 9 met 15L
PC N° 3.6 x \06 U 1M daily chloro2.0 gm. 1M daily 4 days then chloro 1 gm. + PCN 1 gm. P.O. daily
Wo 15.4 kg
Key: ROM-range of motion LOMFROM-full range of motion
N-normal temperature PCN - penicillin amp-ampicillin
of infection in the involved joints, which were tender, erythematous, swollen, and had a decreased range of motion. In all cases, the WBC was elevated with a left shift. The sedimentation rate was also elevated when obtained. CLINICAL PEDIATRICS
blood, right elbow left ankle
December 1975
Cultures of the joint fluid were positive for H. injiuenzae type B in five of seven patients; and the sixth had H. injiuenzae type E. Nospharyngeal cultures were positive for H. influenzae type B when done (three out of three). Bacteremia was present in four of
1147
HARLOW, CHUNG, AND PLOTKIN
TABLE 1. Summary Fever Profile
Joint
ofSeven
Patients with the H lnfluenzae Arthritis (Continued)
Other Treatment
X-ray
Follow-up
102.2°F. N2Y2 days
purulent fluid
day I-incision and drainage
soft tissue swelling elbow
7 wks LOM (50%)
103°--+N at 11th day
purulent fluid
day 1-4 tapknee day I-elbow tap no fluid day 10incision & drainage of left ankle
both knee & ankle soft tissue swelling; then 10 days later lytic lesion left distal fibula
6 wks. elbow good ROM ankle LOM (30%)
102°--+N 3 days
3 cc. purulent fluid
day I-tap day 3-incision & drainage of foot
diffuse soft tissue swelling dorsum foot
good ROM 4 wks.
102° N-8 days
20 cc. purulent fluid
day 1-5 daily tap day 6-incision & drainage of knee
soft tissue swelling knee
good ROM 6 weeks
102°--+N 8th day
3 cc. purulent fluid gram stain g+
l st day-tap 3 cc. purulent fluid 3rd day-2 cc. purulent fluid intra-articular 1 mill PCN instilled on 4th day-2 cc. 5th day-2 cc. 6th day-dry tap
Ist day soft tissue swelling
6 yr. persistent LOM and pain
105°--+ N on 4th day
5 cc. purulent fluid knee
1st day-tap 15 cc-. purulent fluid 8th day-tap knee 15 cc. serupurulent fluid. chloromycetin 15 mg intra-articular given
knee + elbow soft tissue swelling
4 wks. 0-145° ROM persistent synovial thickening
105°--+N in 5 days
purulent fluid
1st day-tap knee 6 cc. pus 2nd day - tap knee 6 cc. pus. PCN 1 million u intraarticular 3rd day -tap knee 6 cc. pus. PCN repeated
knee-soft tissue swelling
2 mos. spica at 4 yrs. FROM with no pain
gent-gentamicin chloro-chloramphenicol
n.g.-no growth naf- nafcillin
four patients tested. All seven had at least one positive culture for H. irifluenzae. Roentgenograms uniformly revealed soft tissue swelling with occasional evidence of joint effusion, but no destruction of bone. Before 1967, antibiotics used in treatment were penicillin and chloramphenicol par-
1148
enterally and intra-articularly. Since that time, intravenous ampicillin has been used for approximately three weeks. Ampicillin was not given intra-articularly. Three cases required surgical intervention because of recurrent effusions, continued pain, and fever after two days of treatment with antiVol. 14 No. 12
CLINICAL PEDIATRICS
HEMOPHILUS SEPTIC ARTHRITIS
biotics. Lysis of fever occurred within two days after surgical decompression. Long-term follow-up was accomplished on four patients, three of whom completely recovered. One patient's ankle joint was completely destroyed. The other three patients were lost to follow-up. Discussion
The optimal treatment for septic joints in children begins with a rapid determination of bacterial etiology by aspiration and proper culture techniques. Whenever a joint is aspirated, the fluid should be evaluated for viscosity and cloudiness and should have a cell count, gram stain for bacteria, culture for mycobacteria and for bacteria including Hemophilus influenwe. Cultivation of H. influenzae requires media containing X and V factors. Therefore, only media such as Levinthal and chocolate agar are suitable, and unless they are employed routinely in culture of septic joints, infection with this organism may be missed. Moreover, although commonly cultures are negative from joint fluid in obvious septic arthritis, if the patient is below two years of age, H. injiuenzae should be strongly suspected. The development of H. injiuenzae arthritis is presumably the result of nasopharyngeal infection leading to bacteremia, during which arthritis, meningitis, cellulitis, or other septic complications may occur. As in the other H. influenzae septic complications, type B is usually the capsular type of the organism involved. We found that commonly an infected joint in a child is assumed to be caused by Staphylococcus aureus and that treatment with an intravenous penicillin such as nafcillin is undertaken. The lack of clinical response should lead one to suspect H. injiuenzae septic arthritis especially in a child less than two years of age. The treatment of septic arthritis in the infant should combine ampicillin with a penicillin active against penicillinaseproducing staphylococci, such as nafcillin,
CLINICAL PEDIATRICS
December 1975
methicillin, or oxacillin. If H. influenzae is isolated from the joint, treatment can then be continued with ampicillin alone for three weeks at a dosage of 150/mg/kg/day in four divided doses, given intravenously or intramuscularly. Joint fluid levels on these parenteral regimens have been shown to be adequate for effective treatment." We do not feel longer therapy with intravenous or oral antibiotics is necessary. If the organism proves to be resistant to ampicillin, chloramphenicol is an excellent alternative. In addition, plaster splints or casts should be used to immobilize the joint for four to six weeks for patient comfort. If the response to one or two joint aspirations is good (in 36 to 48 hours) as determined by rapid decrease of fever, minimal reaccumulation of fluid and good return of painless motion, intravenous ampicillin can be the definitive treatment. If, however, there is slow response or rapid reaccumulation of joint fluid, an incision and drainage of the joint should be immediately done. We believe that an infected hip joint especially should be drained without any attempt at conservative therapy. The blood supply to the femoral head is sensitive to pressure which results in tamponade which in turn will lead to avascular necrosis." References 1. Nelson, J. D., and Koontz, W. C.: Septic arthritis in infants and children: a review of 117 cases. Pediatrics 38: 966, 1966. 2. - - : The bacterial etiology and antibiotic management of septic arthritis in infants and children. Pediatrics 50: 437, 1972. 3. Wall, J. J., ~nd Hunt, D. D.: Acute hematogenous pyarthrosis caused by hemophilus inftuenzae. J. Bone Joint Surg. 50: 1657, 1968. 4. Farrand, R. J.,Johnstone, J. M. S., and Maccabe, A. , F.: Haemophilus osteomyelitis and arthritis. Br. Med. J. 2: 334, 1968. 5. - . - : .Haemophilus inftuenzae type B septicaemia. Br. Med. J. 1: 150, 1969. 6. Nelson, J. D.: Antibiotic concentrations in septic joint effusions. N. Eng!. J. Med. 284: 349, 1971. 7. Soto-Hall, R.: Variation in the intra-articular pressu~e ofthe hip joint in injury and disease. J. Bone Jomt Surg. 46-A: 509, 1965.
1149
