Neonatal Osteomyelitis

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Neonatal

Osteomyelitis

Lavinia Fox, M.D., and Katherine Sprunt, M.D.

From the Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York

ABSTRACT. To evaluate current conservative therapy and document the existence of a recent shift in etiologic agents,

we reviewed the records of 45 infants who developed osteomyetitis within the first ten weeks of life and who were admitted to Babies Hospital (New York) from 1951 through

1976. Emphasis was placed on characteristics and course of the disease, etiologic agents, therapy, and outcome. Illness

was diagnosed within the first two weeks of life in 34 of the 45 infants (73%). Only six had been delivered normally after normal pregnancy and led a normal life before development of osteomyelitis. Infected sites were distinctive in frequency

of involvement of multiple foci (21), of facial bones (10), and of joints contiguous to infected tong bones (22 of 29). Conservative therapy (nonsurgical) seems reasonable for the majority of patients. Of particular interest is documentation of a shift from Staphylococcus aurens as predominant etio-logic agent before 1965 to ,8-hemolytic streptococci, commonly group B, from 1965 through 1976. Data collected from the literature of the 1930s indicate that such shifts have occurred before. Pediatrics 62:535-542, 1978, neonate, osteo-mye/itis, infection.

Osteomyelitis in infancy has been recognized since pre-antibiotic years as an entity distinct from osteomyelitis in older children.’3 Early descriptions of cases are remarkably similar to those found in the most current reviews4 and to those reported here. Recently we became aware of a trend in Babies Hospital (New York) toward increasingly conservative (nonsurgical) therapy and of an apparent shift in common etiologic agent from the Staphylococcus to the

Streptococ-cus.

Accordingly, we reviewed the details of the 45 cases that occurred in the past 25 years (1951 to 1976) to reevaluate therapy as much as possible

in the light of outcome and to document a

possible shift in etiologic agent. The review includes a sufficient number of cases to minimize previously described differences in factors such as sex distribution and sites involved, and to reem-phasize the abnormal early history of infants who develop osteomyelitis and the frequency of mini-mal early signs .of disease, which necessitates

careful attention to detail in the physical exami-nation.

ANALYSIS

Patient Population

The 45 infants included in the study were those who developed bacterial osteomyelitis within the first ten weeks of life and who were admitted to Babies Hospital from 1951 to 1976. Thirty-seven were first seen at Babies Bospital; eight were admitted after initial therapy in other institutions. Twenty-four were male, 21 were female. Eleven were black, one was Japanese-white, and the remaining 33 (73%) were white.

Diagnostic Criteria

Patients were included in the study on the basis of characteristic clinical findings, development of compatible nadiologic abnormalities, and positive cultures of blood or lesions. Thirty-nine met all three criteria. Three of the six exceptions did not have positive x-ray findings. Two of these three had no follow-up roentgenograms taken; the roentgenogram of the other (dental) was equivo-cal. These three patients also had negative blood cultures taken after institution of antibiotic then-apy. Two had positive cultures from the site of infection. These three patients, all presumed to have osteomyelitis of the maxilla, are included on the basis of their typical clinical features.

The other three exceptions lacked positive cultures of blood or lesions, but the clinical and x-ray findings were typical of osteomyelitis. Two patients had been treated initially elsewhere and no record of organism was found in their charts. A “paracolon” bacillus was isolated from one of four

Received September 6, 1977; revision accepted for publica-tion January 11, 1978.

ADDRESS FOR REPRINTS: (K. S.) Box 50, Babies Hospital, 167th Street and Broadway, New York, NY 10032.

at Viet Nam:AAP Sponsored on September 7, 2020 www.aappublications.org/news

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0 0

a:

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7

6

5

1951

I

55

60

65

70

75 YEAR

FIG. 1. Distribution of cases of neonatal osteomyelitis by year of birth. Total cases per five-year period are given above braces.

blood cultures from the third infant who was admitted on the 12th day of symptoms. The organism isolated was considered at the time to be a contaminant.

Year of Onset of Disease

Figure 1 shows the distribution of cases by year. There is no clear evidence of an increased mci-dence of osteomyelitis in the late 1950s as might be expected from the high incidence of staphylo-coccal disease in nurseries in those years.

Age at Diagnosis

Most of the infants (34, on 73%) had clinical signs of osteomyelitis by 2 weeks of age. In 13 of these, osteomyelitis developed by 10 days of age; 5 days was minimum. Among the other babies,

TABLE I

ABNORMALITIES DURING PREGNANCY AND DELIVERY

Abnormality No. of Cases

Pregnancy

Prior fetal toss, bleeding episodes 3 & multiple drug therapy

Bleeding episodes atone 2

Preeclampsia & hypertension 2 Premature separation of placenta 1 Repeated intrauterine transfusions 1

Breast removal at 2 mo 1

Marked obesity 1

History of being “very sick” with 1 no prenatat care

Detivery

Cesarean section 7

Prolonged rupture of membranes 3 (19#{189}hi, 2 days, 1 wk)

Uterine inertia 1

Breech extraction 1

High forceps delivery 1

four showed their first detected clinical signs at 3 weeks of age, two at 4 weeks, and four at 41, 50, 60, and 74 days of age, respectively. Age at onset of illness was not known in one infant who was initially seen elsewhere.

Probable Contributing Etiologic Factors

The clustering of cases in the immediate pen-natal period reflects the importance of associated maternal or infant abnormalities. Only 6 of the 45 infants were delivered normally following normal pregnancies and lived clinically uneventful lives before onset of osteomyelitis. It may be signifi-cant that the age at onset of illness for these six was relatively late, 14 to 36 days.

Contributing Causes

Maternal Problems. A brief history of the pneg-nancy was available for 44 of the 45 mothers. Since many of these histories contained vague references, such as “uneventful” on “uncompli-cated,” it is reasonable to conclude that the evidence was weighted toward normality. How-ever, 12 (27%) of the 44 mothers had some abnormality in the course of their pregnancy (the two twin births were considered normal). Mater-nal abnormalities are shown in Table

I.

One of the mothers with preeclampsia and hypertension also

had

“flu” at six weeks.

Thirteen of the mothers of infants who subse-quently developed osteomyelitis were followed up and delivered of their infants at Sloane Hospi-tal, Columbia Presbyterian Medical Center, and therefore more complete records were available. Four of these pregnancies were abnormal (prema-tune separation of placenta, marked obesity, intrauterine transfusions, or multiple fetal losses with extensive medication during pregnancy).

Delivery Problems. Information on delivery was available for the samt #{149}4-mothers (Table I). at Viet Nam:AAP Sponsored on September 7, 2020

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Signs

Swelling

Fever

Decr. mobility

Erythema

Skin cmd mm. abnorm. Tenderness

G.l. disturbance

54% *k\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\ 30%

23%

\ 65%

14%

2%

ill II I I I I I I

12345 0 5 20 25 30 35

NUMBER OF PATIENTS

FIG. 2. Incidence of presenting signs of osteomyelitis in 43 neonates. Incomplete information was available for two infants who were first seen elsewhere.

Thirteen deliveries were abnormal (30%). Mid-forceps were used in the delivery of the infant born two days after rupture of the membranes. The infant whose membranes ruptured a week before delivery also required breech extraction.

Six of the 13 infants born at Sloane Hospital had abnormal deliveries (membranes ruptured

two

days

and mid-forceps used, membranes ruptured for 19#{189}hours, three cesarean sections, and one breech extraction).

In summary, of 44 pregnancies and deliveries, some abnormality was reported in 21 cases (48%).

Infant Problems. Twenty-four of the infants (56%) who subsequently developed osteomyelitis had a preceding infection which could have led to bactenemia (pustules, furuncles, abscesses, puru-lent umbilicus, otitis media, pneumonia, infected cut-down or puncture sites). One infant with osteomyelitis of the skull had a cephalohematoma which had been aspirated at another hospital and presented to Babies Hospital with pus oozing from the needle track.

Eight additional infants were in potential infec-tious situations, for example, hospitalization with repeated femonal punctures, multiple exchange transfusions, or surgery for pylonic stenosis followed by intravenous therapy. Two of the eight had chickenpox, and one with respiratory distress syndrome (RDS) had cultures from an umbilical artery catheter that were positive for the organism later found in blood and joint aspirates.

Twelve of the 32 infants noted above had, in addition, basic problems that could increase their vulnerability to infection: exchange transfusions for various reasons (3), RDS (4), hypoadnenalism

(1), renal agenesis and hypoplasia (1), and necro-tizing enterocolitis (1). One infant had multiple

.problems that were probably due to congenital

rubella (mother with “flu” at 6 weeks), and one, treated elsewhere before admission to Babies Hospital, had “failed to thrive.”

Ten of the 39 infants whose birth weights were noted in our records weighed less than 2,500 gm at delivery, nine weighed less than 2,000 gm, and three weighed less than 1,500 gm. Eight of the ten with low birth weights were included above as high-risk babies. There remain ten of the 44 infants with early records (23%) who were appar-ently normal at birth and had normal early histories. Only six of these ten were delivered normally following a normal pregnancy.

Presenting Signs

Only four of the infants presented with a “septic” or “toxic” type of illness. Most had a relatively benign onset of infection. Figure 2 shows the incidence of presenting signs in the 43 neonates with osteomyelitis whose records con-tamed this information. Commonly the initial finding was decreased mobility of an extremity, which focused attention on the swelling that was sometimes not conspicuous. Characteristically, as a group, the infants gave little evidence of systemic illness beyond fretfulness, particularly when they were moved. One case was detected by a resident in the course of a well-baby examina-tion when he noted that the infant was not using one leg freely. Another baby was brought to the hospital because of a sudden appearance of lumps. The mother, a pediatric nurse, stated that he had not had a sick day, although the lumps over his ribs and extremities proved to be multi-pie sites of osteomyelitis.

Sites

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+ +

+ + +

- +

- - +

I I

I

I I I I I I I I +

01234

Estimated date of

clinical onset

56

78

9 10-12

DAY

OF

DISEASE

FIG. 3. Time from estimated date of onset of osteomyelitis in retation to x-ray signs of infection. Plus sign indicates positive x-ray reading for osteomyelitis and minus sign indicates negative

reading for osteomyetitis. (I)

>-4

x

U-0

a:

w

z

+

-

-I.

I I

15

20

25

these 21 infants, including most frequently the femur (19 times), the humerus (13 times), and the tibia (10 times). Multiple involvement including facial bones occurred in three infants. Other sites and number of infections were clavicles (4), ribs (2), calcaneus (1), ilium (1), and dorsal spine (1).

In the 24 infants with a single site of infection, long bones were involved in 11. The next most common sites were facial bones in seven, the skull in two, and in one each infection of a rib, scapula, calcaneus, and thumb.

Of the ten infants with facial bone involvement the maxilla was infected in six. The complete syndrome of facial swelling and pus draining from a tooth bud site was described as such in only two.

At least one contiguous joint was infected in 22 of the 29 (76%) with osteomyelitis of the long bones. Septic arthritis was not always commented on in the records. The diagnosis of joint infection was made on the basis of aspiration of pus from the joint, positive cultures from joint fluid, or concurrent on subsequent abnormal x-ray find-ings.

Laboratory Data

Leukocyte and differential blood cell counts on admission were frequently not helpful in diagno-sis in view of the wide range of normal values in the neonate.5 When plotted by age and compared with “normal” findings, two thirds of the admis-sion WBC counts were within the span of normal. The median count for all infants in the series was 17,000/cu mm, with a range from 5,100 (in a 7-day-old infant) to 39,000/cu mm (in a 12-day-old infant).

The ESR was determined at the time of admis-sion on 21 infants; this proved to be more helpful in diagnosis and follow-up. In only five cases were the rates below 40 mm/hr. In two of these five patients (ESR of 1 and 6 mm), the WBC count was 5,100 and 8,300/cu mm, respectively, with

46% and 47% polymorphonuclear cells and a

slight shift to the left in the differential blood cell count of the first baby only. The WBC counts of the other three with low ESRs varied from 13,300

to 26,650/cu mm.

Roentgenograms

All but three of the 45 infants had x-ray findings indicative of osteomyelitis (i.e., bone changes in addition to soft tissue swelling). Twenty-three of the remaining 42 had positive x-ray findings at the time of admission to the hospital.

To determine the length of time required for x-ray findings of early bone changes to develop in the neonate, an attempt was made to estimate from the history the probable time of onset of osteomyelitis. Estimates of onset were made for

34

infants

and the results are tabulated in Figure

3. It is evident that the majority of roentgeno-grams showed positive findings by the 10th to 12th day after the estimated date of clinical onset of disease.

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7 6

5

4

3

2

1951

S. aureus 24/5 S. aureus before 1965 (96%)

ProbableE.coliStreptococcus,group group superimposedB strep. p< 0.014(0/ * * S. aureus 1965 -1976 (29%)

,, No etiologic agent recovered “ 14(5)

D Death

FIG. 4. Shift in causative agents of neonatal osteomyelitis, 1951 through 1976. Asterisk indicates

cases of multiple organisms.

TABLE II

CAUSATIVE AGENTS

bHdIBL

55

60 YEARS

tive” evidence of osteomyelitis of the neck of the femur on the 12th day. The third infant who had cellulitis of the lower leg on the fourth day of age was considered clinically to have tibial osteomye-litis on the fifth day. His roentgenographic find-ings were negative on the fourth, sixth, and eighth days of illness and positive on the 16th day.

Causative Agents

Among the 45 infants studied, no causative agent was found in three and the organisms detected in two others were questionable in identification or causal relationship to the osteo-myelitis. A Gram-negative motile bacillus then

(1963) called “paracolon” was found in one of three blood cultures taken on admission from one of the latter two infants. The organism was recorded in the hospital chart as a probable contaminant. Streptococcus viridans was isolated from one of three blood cultures taken from the other infant (1965). The mother carried a /3-hemolytic Streptococcus in her vaginal flora. This infant may have been infected by an a-hemolytic mutant of a group B /3-hemolytic Streptococcus.

If the first four infants are considered to be without etiologic diagnosis, and the last infant as probably infected with a group B Streptococcus, the distnibution of causative agents is as shown in

Table II.

Three infants were infected simultaneously with two organisms, one of which in each instance was a group A Streptococcus. Staphylococcus

aureus

and group A streptococci were isolated

from two blood cultures from one infant and from an abscess of his left kidney. Group A streptococci and Escherichia coli were found in two blood

65 70 75

cultures and the urine of another; only the strep-tococci grew from the lesion. The third infant had a group A Streptococcus isolated from the shoul-den joint and a group B Streptococcus from the blood. As judged by bacitnacin disk resistance, fluorescent antibody uptake, Lancefield precipi-tin tests, and biochemical reactions, these orga-nisms were different.

There was a clear shift in causative agents over the time span of this study. As shown in Figure 4, 24 of 25 agents isolated before 1965 were Staph.

aureus. The exception was an E. coli. From 1965

on, however, Staph. aureus was found in only 5 of 16 patients from whom organisms were isolated, and in one of these it was present in conjunction

Org anism No. of Cases

Single organism

Staph. aureus 28

E. co/i 4

fl-Hemolytic Streptococcus

Group A 1

Group B 4

Enterococcus 1

Multiple organisms

Group A hemolytic Streptococ- 1

ens + Staph. aureus

Group A hemotytic Streptococ- 1

Cu’s + E. co/i

Group A hemolytic Streptococ- 1

cus + group B hemolytic Strep-tococcus

No organism 4

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with a group A Streptococcus. Streptococci were isolated from nine of the patients, three times as mixed organisms (ten streptococcal isolates). Five of the streptococci were group B, the first of which was found in 1965.

Therapy

Therapy varied considerably in the period from 1951 to 1976. In the earlier years most patients received a penicillin preparation combined with chloramphenicoi and sulfisoxazole. In recent years the tendency has been toward the use of a single antibiotic, although some streptococcal infections were treated with an aminoglycoside for the first few days in addition to long-term therapy with penicillin in high dosage.

Throughout the period of study antibiotics were given parenterally for at least a week, except in five patients. Three of these infants with osteomyeiitis of the thumb, orbit, and clavicle, respectively, were treated parenterally for four days. One with an infected maxilla was treated for six days. The fifth infant had had two intermittent one-week courses of penicillin parenterally for swelling of the face before admission, when he already had extensive damage. After surgical drainage of his extensive mandibular disease, he received chloramphenicol intravenously for only a few hours after surgery; after this, the drug was given orally for eight days. The brief parenteral courses of therapy were apparently successful in all of these patients.

Because of the varied forms of therapy, the effect of its application becomes the most infor-mative aspect for analysis. Of the total group, including therapy received before admission, three infants received antibiotics (orally and parenterally) for less than two weeks. All three made an uneventful recovery. Surgical drainage accompanied medical therapy in two of these infants: one with osteomyelitis of the orbit was treated for three days, the other with

osteomyeli-tis

of the distal phalanx of the thumb for 12 days. The infant who was not subjected to drainage was treated for ten days for osteomyelitis of the maxilla.

Four infants were treated for approximately three weeks. Two with osteomyelitis of the long bones (single site in one and two sites in the other) responded well to therapy, had no other compli-cations of sepsis or therapy, and did not have relapse.

A third

infant admitted in 1953 died of over-wheiming superinfection with “B. proteus” in his

20th

day

of antibiotic treatment. His initial orga-nism, Staph. aureus, was resistant to penicillin,

chloramphenicol, and bacitracin. Therapy was therefore changed from parenteral aqueous peni-cillin, 12 million units/day, and streptomycin, 60 mg twice a day, to oral oxytetracycline (Terramy-cin), 200 mg/kg/day for five days, followed by “Magnamycin,” 50 mg/kg/day for five days, and finally by streptomycin again and sulfisoxazole.

At

autopsy the baby had septicemia, meningitis, and abscesses, but the osteomyelitis of the left proximal tibia was described as healed.

The fourth infant represents the only probable postadmission relapse in the series as a result of inadequate medical therapy. This 19-day-old infant presented in 1958 with a sudden onset of fever to 38.#{176}C(102#{176}F),flaccid paralysis of the left ann, and whimpering and lethargy for about 12 hours before admission. The blood culture taken on admission yielded Staph. aureus sensitive to most antibiotics tested, including penicillin. His admission roentgenogram was suggestive of osteo-myelitis of the proximal left humerus. The infant received 5 million units of penicillin, 100 mg/kg of chloramphenicol intravenously, and 150 mg/kg of sulfisoxazole intramuscularly for 20 days. The clinical response was judged to be good. Antibiot-ic therapy was stopped on the 20th day when his

ESR had

dropped from 41 to 13 mm/hr and his WBC count had dropped from 31,000 to 15,000/

cu mm. Eight days later he developed tempera-hire elevations to 39.4#{176}C(103#{176}F),his ESR rose to

114

mm/hr and his WBC count rose to 23,000/cu mm. He was considered without proof (three negative blood cultures) to be in relapse and was given a second course of the same parenteral antibiotics for two weeks. This led to rapid clinical improvement with no subsequent re-lapse.

All other infants were treated for longer than three weeks; all but one recovered uneventfully. The exception returned with a superficial abscess in the area of prior surgery performed at another hospital. After removal of a small piece of rubber, he too responded well without further complica-lions.

Surgical Drainage

Evaluation of the need for a surgical approach is difficult because of varying severity of disease and change in causative agent. Since most residua occurred in those with long bone and joint involvement (see below), this group was reviewed to determine, if possible, what role surgical mci-sion and drainage (I&D), aspiration alone, and no surgery play in determining outcome. Nine of the 13 patients with residual damage and clear early records had I&D, three had aspiration, and one

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had no form of drainage. Three of the seven with long bone and joint involvement without residua had an I&D, three had aspiration alone, and one

had drainage.

If all patients are considered, those seen before 1965 (Staph. aureus interval) had a 50% residual daniage rate. Five of the 17 (29%) born in 1965 on later (streptococcal interval) suffered residua. Although no conclusion can be drawn from these totals alone, there is no evidence that the current trend toward minimal surgical intervention is harmful. For instance, both of the most recent patients with osteomyelitis of the femur and involvement of the hip joint (group B streptococ-ci) were treated with antibiotics and diagnostic aspiration alone. Both are free of residua. Of the last ten patients, two had residua. Each had surgical drainage of the shoulder and hip, respec-lively. The former with group B streptococcal infection was seen very late and masses of extra-periosteal pus required drainage. Clinical damage in the latter (E. coli) is becoming minimally detectable with passage of time (three years).

RESULTS

All but four surviving infants have been avail-able for follow-up. The shortest follow-up interval is a few months, the longest, 23 years. For most patients the interval has been 3 to 1 1 years.

There were two deaths in the series. One, noted above, was caused by overwhelming supeninfec-tion when the osteomyelitis was healing. The other was probably secondary to the same sepsis which produced the osteomyelitis. This patient was admitted in 1952 with sepsis and multiple sites of osteomyelitis from which Staph. aureus

resistant to penicillin was isolated. Although she had responded reasonably well to therapy, exten-sive generalized infection was obvious on admis-sion. After discharge from the hospital she suffered from complications secondary to extrahe-patic portal obstruction and hypertension, glomenilonephritis, and residua of her extensive osteomyelitis. She died at 7 years of age of acute

Aspergillus meningoencephalitis.

All survivors were able to function reasonably well in spite of residual deficits in some (total of 19). Significant residual damage correlated best with long bone and contiguous joint involvement. Of the 22 patients with associated joint involve-ment, 15 (68%) had persistent, clinically evident damage of some degree. The seven patients with long bone disease and no evidence of joint infec-tion were uniformly normal on follow-up.

Residual damage in those with long bone and joint infection usually consisted of shortening of

an extremity (ten patients) and decreased

mobili-ty

of a joint (five patients). Two, not included in the foregoing, had hip damage which resolved clinically within the first year of follow-up. Three patients required osteomyotomy to equalize extremity length, and an additional patient underwent epiphysectomy.

The patients with the next most frequent persistent defects were those with facial bone involvement. Of the nine patients followed up, three had significant residua. All three had dental problems secondary to destruction of tooth buds. In addition, two of the three patients with seques-tra were in this group. Both had had mandibular infection, one as a single site of involvement and one with severe multiple site disease who also required osteomyotomy (as mentioned above).

The only other persistent clinically evident deficit occurred in a severely ill child who had multiple foci of infection. Two vertebrae were virtually destroyed by osteomyelitis with result-ing severe kyphosis.

DISCUSSION

Of interest in the group of 45 infants with neonatal osteomyelitis are the early age of onset (73% at less than 2 weeks of age), the frequency of pregnancy or delivery problems, and the frequen-cy of peninatal infections or unusual experience in the early life of the infant. Only six of the infants in this series were delivered normally after a normal pregnancy and had a clinically normal life prior to recognition of their osteomyelitis. Outstanding features that differ from the disease in older children are benign onset and course in most neonates, frequency of involvement of multiple foci (47% in neonates versus 8% in patients of all ages6), frequency of involvement of contiguous joints in those with long bone infec-lion (76% versus 14% with “effusion”), and frequency of involvement of facial bones (10 of 45 versus 0 of 626). These findings have been noted over the years with varying figures and empha-sis.4-6’9 The data noted here include a sufficient number of cases to provide reasonably reliable statistics.

Early diagnosis in the neonate is primarily clinical with strong support from x-ray findings, which were positive on admission in 23 of 42 (55%) in this series and up to 100% in prior series.3 The admission ESR was helpful in 16 of 21 (76%) patients, but the wide range of normal of other laboratory findings such as WBC and differential counts render these tests relatively useless.

Reevaluation of therapy on the basis of the data is difficult because of the variations in methods of

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care secondary to the wide time span covered and

the change in causative agents. We were

surprised to note the frequency of relatively short-term antibiotic therapy in the early cases which was apparently successful with and with-out concomitant surgery. We do not favor mini-mal therapy, however, and do not consider that we have seen enough patients treated for less than three weeks to recommend shorter courses of antibiotics. Nevertheless, we see nothing in the data to counter the current trend in our institu-tion toward a conservative nonsurgical approach to therapy, especially when the diagnosis has been made early in the disease process and masses of extnapeniosteal pus are not present.

The shift in causative agents noted in this series is particularly interesting. The data presented

here document the marked predominance of

Staph. aureus as an agent from 1951 through 1964 and a shift to predominance of the Streptococcus,

usually of group B, after 1964. A review of the literature shows that in the 1930s the predomi-nant organisms were hemolytic streptococci. Donovan’s article on osteomyelitis in the 1940 edition of Holt’s Textbook of Pediatrics7 refers to streptococci as the most frequent etiologic agent in infancy. Green in 1935’ found that streptococci caused 63% of the disease under 2 years of age

(“/o Streptococcus hemolyticus”). Hutter,8 in 1948, discussed two groups of cases, those

occuning from 1934 to 1943 and those between

1943

and

1947. He excluded the streptococcal cases in the first group because none was found for comparative purposes after 1943. Stone9 reported four cases of neonatal osteomyelitis; the first in 1935 was due to a Streptococcus and the other three in the 1940s were due to staphylococ-ci.9 Without recognized bias, we have collected from the literature cases occurring in the 1930s and early 1940s in which causative agents were listed.2-88 Twenty-nine cases from this collec-tion were caused by staphylococci, 55 by strepto-cocci (61%), and 6 by other organisms. After the mid-1940 interval, staphylococci predominated strongly in all series reviewed.

The two recent reviews of cases (1959 to 1973’s and 1965 to 1972) do not note a shift to strepto-cocci. The latter series lists nine cases of Staph. aureus to one of group A hemolytic streptococci; a shift was not present. The former, discussing children under 2 years of age, listed 12 cases due to Staph. aureus and 3 due to streptococci. There

were two additional infants with Staph. aureus

combined with streptococci. There could have been a shift in causative agent, but timing was not noted. Since there has been a recent marked increase in incidence of group B streptococci in nurseries in diverse localities, and since these organisms have been reported recently as causing neonatal osteomyelitis,2 it seems likely that the shift is not peculiar to our area and has not occurred in all localities with the same rapidity.

REFERENCES

1. Green Wi’: Osteomyelitis in infancy. JAMA 105:1835, 1935.

2. Dittehunt RB: Osteomyetitis in infants. Surg Gynecol Obstet 6:96, 1935.

3. Clarke AM: Neonatal osteomyetitis: A disease different from osteomyelitis of older children. Med I Aust

1:237, 1958.

4. Weissberg ED, Smith AL, Smith DH: Clinicat features of neonatal osteomyelitis. Pediatrics 53:505, 1974. 5. Behrman RE (ed): Neonatology. St Louis, CV Mosby Co.

1973, p 654.

6. Waidvoget FA, Medoff G, Swartz MN: Osteomyetitis: A review of clinical features, therapeutic considera-tions and unusual aspects. N Engl I Med 282:198, 1970.

7. Donovan EJ: Osteomyelitis, in Holt LE, Jr, McIntosh RD, (eds): Holt’s Disease of infancy and Childhood. New York, Appleton-Century Co, Inc, 1939, pp

777-790.

8. Hutter CG: New concepts of osteomyelitis in the newborn infant. I Pediatr 32:522, 1948.

9. Stone 5: Osteomyetitis of the long bones in the newborn. Am I Dis child 64:680, 1942.

10. Campbell LA: Septicaemia in children. Can Med Assoc I

24:674, 1931.

11. Dunham EC: Septicemia in the newborn. Am I Dis Child 45:229, 1933.

12. Mount WB: Septicemia in the newborn. Am I Obstet Gynecol 29:126, 1935.

13. Green \VT, Shannon JG: Osteomyelitis of infants. Arch

Surg 32:462, 1936.

14. Cass JM: Staphylococcus aureus infection of the long bones in the newly born. Arch Dis Child 15:55,

1940.

15. Greenyard J: Acute hematogenous osteomyelitis in infancy. Med C/in North Am 30: 135, 1946.

16. Thompson J, Lewis IC: Osteomyelitis in the newborn. Arch Dis Child 25:273, 1950.

17. Blanche DW: Osteomyelitis in infants. I Bone loint Surg

34:71, 1952.

18. James T: Acute osteomyelitis in infancy and early childhood. Br I Surg 41:87, 1953.

19. Dich VA, Nelson JD, Hattalin KC: Osteomyetitis in infants and children: A review of 163 cases. Am I Iis Child 129:1273, 1975.

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1978;62;535

Pediatrics

Lavinia Fox and Katherine Sprunt