Effect of Cefotaxime or Ceftriaxone Treatment on Nasopharyngeal ...

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Sept. 1995, p. 2150–2152 0066-4804/95/$04.0010 Copyright q 1995, American Society for Microbiology

Vol. 39, No. 9

Effect of Cefotaxime or Ceftriaxone Treatment on Nasopharyngeal Haemophilus influenzae Type b Colonization in Children PAUL N. GOLDWATER* Microbiology Department, The Women’s and Children’s Hospital, North Adelaide, 5006, Australia Received 8 December 1994/Returned for modification 28 March 1995/Accepted 12 July 1995

The effects of cefotaxime and ceftriaxone treatment on nasopharyngeal carriage of Haemophilus influenzae type b (Hib) were prospectively studied with 53 children with invasive Hib disease. Nasopharyngeal aspirates were monitored during therapy. Hib was eliminated within 2 days in 92% of patients and was eliminated in all patients after the third day of antibiotic treatment.

normally sterile site or from epiglottis swabs (in clinically diagnosed cases of epiglottitis). The patients included 18 with meningitis, 22 with epiglottitis, 8 with periorbital cellulitis, 3 with cellulitis of another site, 1 with septic arthritis, and 1 with pneumonia. The mean age was 30.6 months (6 23.7 months; range, 2.3 to 104 months). Demographic details about the patients are set out in Table 1. Twenty-one of the 22 epiglottitis patients had epiglottic swabs done at the time of tracheal intubation. Twenty-one of the remaining 31 patients had NPAs collected within 24 h of admission, and all patients found positive had a further NPA collected within 48 h. The flow chart in Fig. 1 indicates the specimens collected and times of collection together with culture results. Samples were taken from 36 patients between 24 and 48 h from commencement of therapy. Of these, 30 were re-samples. Four patients (two with epiglottitis [CTX] and two with meningitis [one treated with CTX and one treated with CRO]) had scanty growth of Hib (one to five colonies) from NPAs at 25.8, 37.2, 36, and 40.8 h, respectively. These patients were negative on resampling within a further 24 h. Thus, cumulatively, 49 of 53 (92.4%) patients had negative NPAs between 24 and 48 h after commencement of therapy, and all patients ceased to have detectable colonization with Hib after 3 days of CTX or CRO therapy. BC results together with preadmission antibiotic exposure are set out in Table 2. It is noteworthy that only 5 of 17 (29.4%) patients exposed to antibiotics immediately prior to admission had positive NPAs at admission compared with 20 of 32 (70.3%) patients who had not received previous antibiotic (P 5 0.027; Fisher’s exact test). It is well known that ampicillin and/or chloramphenicol fails

Authoritative guidelines (1, 3, 5) have led to the routine practice of providing rifampin prophylaxis to family members and other close contacts of index patients with Haemophilus influenzae type b (Hib) disease in order to prevent secondary spread of infection. Often, as part of the prophylaxis, the index patient receives rifampin as well as the contacts. Because ampicillin and/or chloramphenicol do not eliminate nasopharyngeal carriage of Hib, a rifampin prophylaxis regimen was devised. Widespread ampicillin resistance in Hib (30% in this study) necessitates the use of the broad-spectrum cephalosporins (cefotaxime [CTX], ceftriaxone [CRO], etc.), which have become the mainstay of therapy for invasive Hib disease. Because there have been no published studies that specifically address the effects of broad-spectrum cephalosporins on nasopharyngeal carriage of Hib, a prospective study of the effects of CTX and CRO on Hib carriage was conducted. The results indicate that a change in infection control practices should be considered as should the approach to prophylaxis with rifampin if children have received CTX or CRO. Nasophyngeal aspirates (NPAs) and/or epiglottic swabs were obtained (within 24 h of admission) from 53 children admitted to the Adelaide Children’s Hospital for suspected invasive Hib disease. NPAs were collected with a suction catheter (French, gauge 7 or 8) and a specimen trap. Catheter contents were rinsed with 5 ml of sterile N saline, the suspension was centrifuged at 5,000 rpm for 15 min, and the pellet was resuspended in 100 ml of saline, streaked onto chocolate blood agar, and incubated overnight at 378C in 5% CO2. Hib was identified by routine methods, and antibiotic susceptibility was tested with National Committee for Clinical Laboratory Standards methodology (7a). If Hib was grown from the first NPA, a second NPA was, where possible, collected within 48 h. Blood cultures (BCs) were obtained from all but three patients upon admission. Other investigations, such as lumbar puncture, were carried out where clinically indicated. Epiglottic swabs (instead of NPAs) were obtained at the time of intubation from 21 of 22 patients admitted with acute epiglottitis. Treatment (CTX or CRO) was assigned by the admitting team. The study was approved by the Adelaide Children’s Hospital Research Ethics Committee. A total of 53 patients (25 males and 28 females) with invasive Hib disease were diagnosed by isolation of Hib from a

TABLE 1. Sex, age, diagnosis, and antibiotic data for patients in this study Value for treatment with: Characteristic

No. of males No. of females Total no. of patients Mean age (mo [6SD]) No. diagnosed with: Meningitis Epiglottitis Cellulitis Pneumonia Septic arthritis

* Mailing address: Microbiology Department, The Women’s and Children’s Hospital, North Adelaide 5006, Australia. Phone: 61 8 204 7432. Fax: 61 8 204 6051. 2150

CTX

CRO

22 22 44 29.5 6 23.6

3 6 9 33.1 6 34.6

12 19 11 1 1

6 3

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NOTES

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TABLE 2. Effect of preadmission exposure to antibiotics on NPA and BC results No. of patients witha: Preadmission antibiotic (n 5 17)

No preadmission antibiotic (n 5 32)

P

Admission NPA Hib positive Hib negative

5 12

20 12

0.027

BC Hib positive Hib negative

13 4

28 4

NSb

Result

a b

Preadmission antibiotic exposure status was unknown for 4 of 53 patients. NS, not significant.

to eliminate nasopharyngeal carriage of Hib (1). In Table 3, the Hib clearance rate is compared with rates obtained by others using ampicillin and chloramphenicol (4–6). Such therapy left 9 to 23% of patients colonized after 4 days of treatment, whereas in the CTX-CRO study, Hib was eliminated within 48 h from the commencement of therapy in 92% of patients. It is noteworthy that the three previous studies used cotton pharyngeal swabs, whereas this study used NPAs. Therefore, differences in the values could reflect the method of collection; however, the initial colonization rate in this study was the same as that in two of the studies cited (2, 4), which would indicate the collection methods were comparable. The dosage protocols for intravenous CRO were 100 mg/kg of body weight once daily for meningitis and 50 mg/kg once daily for epiglottitis, and the dosage protocols for CTX were 50 mg/kg/6 h (200 mg/kg/day) for meningitis and 100 mg/kg/day for other Hib disease. These protocols were followed closely. Antibiotic susceptibilities of the Hib isolates showed that 13 of the 43 (30.2%) isolates tested were resistant to ampicillin. Resistance to chloramphenicol was detected in two isolates. No patients received rifampin during the study. It is known that CRO successfully eliminates nasopharyngeal carriage of Neisseria meningitidis (8). This knowledge, together with the limited value of rifampin in preventing Hib disease (4), encouraged the present study of the effects of broad-spectrum cephalosporins on nasopharyngeal carriage of Hib during therapy. The advent of Hib conjugate vaccines has had an impact not only on rates of Hib disease but also on Hib carriage in vaccinees. In Australia, Hib disease was common at the time of this study, with up to 700 cases of invasive disease reported annually (7). Hib conjugate vaccines were licensed in 1993, and the incidence of disease or carriage is falling as vaccine uptake rates increase. In countries not yet using the

FIG. 1. Flowchart of sequential culture results.

vaccine, Hib disease will continue to be a common problem. Thus, the results of this study remain relevant to the management of Hib disease, when it occurs, and the prevention of secondary cases. It is noteworthy, however, that at the Adelaide Children’s Hospital, only one patient has been readmitted with a second episode of Hib infection several months after the initial infection was treated with CTX. For comparison, the total number of patients treated with CTX or CRO for invasive Hib disease in the prevaccination era (1985 to 1992) was 217 (5a), which indicates that second-episode disease is a rare event after treatment with these broad-spectrum cephalosporins. Although strain characteristics were not examined in the example mentioned above, it is possible the reinfecting strain was different from the initial strain. Obtaining postdischarge follow-up NPAs was not feasible in

TABLE 3. Comparison of Hib nasopharyngeal colonizations by type and duration of therapy No. positive/no. cultured (%)a Day

1 2 3 4 a b

Li and Wald (6); ampicillin 1 gentamicin (most treated)

Gilbert et al. (4); chloramphenicol (80% treated)

Alpert et al. (2); ampicillin 1 chloramphenicol

40/44 (91) 0/7 3/4 (75) 8/35 (23)

33/48 (69) 5/31 (16) 4/38 (11) 4/47 (9)

21/35 (60)

Additional data are derived from the studies cited. Cumulative total.

6/35 (17)

This study CTX

CRO

Total

26/38 (68) 9/32 (28) 0/9 0/44b

4/8 (50) 1/4 (25) 0/4 0/9b

30/46 (65) 10/36 (28) 0/13 0/53b

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NOTES

this study but would be needed in a future study to assess the frequency of recolonization with Hib; however, second-episode disease or secondary cases are rare in our experience. Recolonization rates reflect the prevalence of the organism in the community and the various exposure-risk settings for the individual child. On the basis of this study, we can conclude that barrier nursing measures can be removed after 3 days of intravenous CTX or CRO therapy and that treatment of the index patient with rifampin can almost certainly be avoided if these antibiotics have been given at the recommended dosage for at least 72 h. The expert technical assistance of the following members of the Adelaide Children’s Hospital Microbiology Department is gratefully acknowledged: Linda Wurfel, Andrew Moore, Peter Van Leeuwen, Stav Dimitriou, and Grant Emmerson. Special thanks are given to Andrew Lawrence for kindly providing the historical data on Hib disease. REFERENCES 1. Advisory Committee on Immunization Practices. 1986. Recommendations of the Immunization Practices Advisory Committee (ACIP). Update: prevention of Haemophilus influenzae type b disease. Morbid. Mortal. Weekly Rep. 35: 170–174, 179–180.

ANTIMICROB. AGENTS CHEMOTHER. 2. Alpert, G., J. M. Campos, D. R. Smith, S. J. Barenkamp, and G. R. Fleisher. 1985. Incidence and persistence of Haemophilus influenzae type b upper airway colonization in patients with meningitis. J. Pediatr. 107:555– 557. 3. Cartwright, K. A. V., N. T. Begg, and D. Hull. 1991. Chemoprophylaxis for secondary Haemophilus influenzae type b disease. Commun. Dis. Rep. Rev. 1:2–6. 4. Gilbert, G. L., S. J. MacInnes, and I. A. Guise. 1991. Rifampicin prophylaxis for throat carriage of Haemophilus influenzae type b in patients with invasive disease and their contacts. Br. Med. J. 302:1432–1435. 5. Isaacs, D., M. Ferson, G. L. Gilbert, K. Grimwood, and P. McIntyre. 1994. Royal Australasian College of Physicians Position Paper. Chemoprophylaxis for Haemophilus and meningococcal infections. J. Paediatr. Child Health 30:9–11. 5a.Lawrence, A. Personal communication. 6. Li, K. I., and E. R. Wald. 1986. Use of rifampicin in Haemophilus influenzae type b infections. Am. J. Dis. Child. 140:381–385. 7. McIntyre, P. 1992. Invasive Haemophilus influenzae type b disease in Australia: the beginning of the end? Med. J. Aust. 156:516–518. 7a.National Committee for Clinical Laboratory Standards. 1990. Performance standards for antimicrobial disk susceptibility tests. Approved standard M2A4. National Committee for Clinical Laboratory Standards, Villanova, Pa. 8. Schwartz, B., A. Al-Tobaiqi, A. Al-Ruwais, R. E. Fontaine, J. A’Ashi, A. W. Lighthower, C. V. Broome, and S. I. Music. 1988. Comparative efficacy of ceftriaxone and rifampicin in eradicating pharyngeal carriage of group A Neisseria meningitidis. Lancet i:1239–1242.