An in vitro study of the activity of 10 oral agents against 153 pediatric isolates of Streptococcus pneumoniae identified moxifloxacin and levofloxacin as the most active agents regardless of penicillin or macrolide susceptibility. Moxifloxacin inhibited all strains at 0.25 μg/ml and was 8- to 16-fold more potent than levofloxacin.

An in vitro study of the activity of 9 agents against 181 US pediatric isolates of Streptococcus pneumoniae identified imipenem and faropenem as the most active agents. Overall, faropenem was the most potent oral agent inhibiting 98% of isolates at 1 microg/mL.

To The Editors: We read with interest the recent article by Principi et al. studying risk factors and prevalence of nasopharyngeal carriage of respiratory pathogens in children.1 Although we agree with many of the conclusions, we are concerned about direct comparisons between the prevalence of respiratory pathogens found in this study and in other investigations, including our own.2, 3 Reviewing the methodology of specimen collection, we note that the specimens were obtained with a bent swab passed "through the mouth" and held in the oropharynx for 5 s. Although we applaud the investigators for holding the specimen for that duration, we would like to point out to readers of the journal that most published studies2-6 utilized swabs passed "nasally" into the nasopharynx. This difference in methodology alone may account for the different prevalence of respiratory pathogens found by Principi et al. We are aware of no data directly comparing such oropharyngeal cultures to cultures obtained through the nose. One group of investigators suggested that they performed both oropharyngeal and nasopharyngeal cultures to improve their yield of respiratory pathogens.7 However, no data were presented to show that culturing the oropharynx increased the yield of pneumococci. The cultures done by Principi et al. may reflect oropharyngeal colonization, a subtle but important methodologic difference. Daniel J. Boken, M.D. Stephen A. Chartrand, M.D. Division of Pediatric Infectious Diseases; Department of Pediatrics; Creighton University School of Medicine; Omaha, NE

A panel of 279 clinical isolates of Gram-positive cocci and Gram-negative bacilli with varying levels of resistance to ciprofloxacin were analysed for susceptibility to moxifloxacin, ciprofloxacin, ofloxacin and nalidixic acid. Moxifloxacin was eight- to 32-fold more potent than ciprofloxacin and ofloxacin against staphylococci and Streptococcus pneumoniae, and equivalent to eight-fold more potent against enterococci. Although ciprofloxacin was intrinsically more potent than the other quinolones against highly susceptible Gram-negative isolates, the percentages of Gram-negative isolates susceptible to 1 mg/L of moxifloxacin or ciprofloxacin, or 2 mg/L of ofloxacin were 78%, 80% and 76%, indicating in-vitro equivalence of the agents against a collection that included isolates with diminished quinolone susceptibility. Staphylococci were analysed according to their ciprofloxacin susceptibility status. As ciprofloxacin resistance increased to high levels, all quinolone MICs increased, but moxifloxacin and ofloxacin MICs increased less than ciprofloxacin MICs. In mutational studies moxifloxacin inhibited more mutants (69%) at a concentration of 1 mg/L than did ciprofloxacin (63%) at 1 mg/L or ofloxacin at 2 mg/L (31%). The study indicated that moxifloxacin is more potent than ciprofloxacin and ofloxacin against Gram-positive pathogens, may be comparable in activity against less quinolone-susceptible Gram-negative isolates (other than Pseudomonas aeruginosa), and is less affected than ciprofloxacin by mechanisms responsible for increasing quinolone resistance in staphylococci.

MEISSNER, H. CODY MD; WELLIVER, ROBERT C. MD; CHARTRAND, STEPHAN A. MD; LAW, BARBARA J. MD; WEISMAN, LEONARD E. MD; DORKIN, HENRY L. MD; RODRIGUEZ, WILLIAM J. MD Author Information

Acute Otitis Media in the 1990s: The Impact of Antibiotic Resistance Stephen A Chartrand, MD, , and , MD Alice Pong, MD, , MD Stephen A Chartrand, MD and Alice Pong, MD Pediatric Annals, 2013;27(2):86–95Published Online:February 01, 1998https://doi.org/10.3928/0090-4481-19980201-06Cited by:12View Full TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail SectionsMore1. McCraig LF. Hughes JM. Trends in antimicrobial drug prescribing among officebased physicians in the United Stales. JAMA. 1995;273:214-219. Google Scholar2 Marchant CD, Cailin SA, Johnson CE, Shurin PA. Measuring the comparative efficacy of antibacterial agents fot acute otitis media: the "Pollyantia phenomenon." J Pediatr.1992;120:72-77. Google Scholar3. Klein JO. Teele DW. Pelton Sl. New concepts in otitis media: results of investigations of the greater Boston otitis media study group. Adii Pedina. 1992:39:127-156. Google Scholar4. Chow AW, Hall CB, Klein JO, Kammer RB, Meyer RD, Remington JS. Evaluation of new anti-infective drugs for the treatment of respiratory tract infections. Clin infect is. 1992;15(Suppl i):S62-88. Google Scholar5. Klein JO, Teele DW. Isolation of viruses and mycoplasmas from middle ear effusions; a review. Ann Otol Rhinol Laryngol. 1976;85(2 Suppl 25 pt 2):140-144. Google Scholar6. Nikaido H. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 1994:264:382-388. Google Scholar7. Carlin SA, Marchant CD, Shurin PA, Johnson CE, Super DM, RehmusJM. Host factors and early therapeutic response in acute otitis media. J Pediatr. 1991;118:178-183. Google Scholar8. Sutcliffe J, Tait-Kamradt A, Wondrack L. Streptococcus pneumoniae and Streptococcus pyogenes resistant to macro! ides but sensitive ro clindamycin a common resistance pattern mediated by an efflux system. Antimicrob Agents Chemother. 1996;40:1817-1824. Google Scholar9. National Committee for Clinical Laboratory Standards. Performance Standards far Antimicrobial Susceptibility Testing; eighth informational supplement. M100-S8, vol. 18. Wayne, PA: National Committee for Clinical Laboratory Standards; 1998. Google Scholar10. Appelbaum PC. Antimicrobial resistance in Streptococcus pneumoniae an overview. Clin Infect Dis 1992:15:77-83. Google Scholar11. Friedland IR1 McCracken CH. Management of infection caused by antibiotic- resistane Streptococcus pneumoniae. N Engl J Med. 1994:331:377-382. Google Scholar12. Block SL, Harrison CJ, Hedrick JA, Tyler RD, Smith RA, Keegan E, Chartrand SA. Penicillin resistant Streptococcus pneumonias in acute otiti; media; risk factors, susceptibility patterns, and antimicrobial management. Pedian Infect Dis J. 1995:14-751-759. Google Scholar13. Boken DJ, Chartrand SA, Goering RV, Krüger R. Harrison CJ. Colonization with penicillin-resistant Streptococcus pneumoniae in a child-care center Pediatr Infect Dis J. 1995;14:879-884. Google Scholar14. Dowell SF, Jayaraman M, Keyserling H, Kokzak M, Schwanz B. Currrent antimicrobial use fot pediatrie upper respiratory infections. In: Program and Abj tracts of the Infectious Disease Society of America 35t/i Annual Meeting, San Francisco, September 13-16, 1997. (poster 377). Google Scholar15. Reichlet MR, Allphin AA, Breiman RF, Schreiber JR. Arnold JE. McDougal LK, Facklam RR, Boierbaum B. Walton RO, et al. The spread of multiply resistant Streptococcus pneumoruoi at a day care center in Ohio. J infect Dis. 1992;166:13461353. Google Scholar16. Doem GV. Resistance among problem respiratory pathogens in pediatrics. Pediatr infect Dis J. 1995:14:420-423 Google Scholar17. Brook I, Gober AE. Monthly changes in the rateof recovery of penicillin-resistant organisms from children. Pediarr Infect Dis J. 1997;16:255-257. Google Scholar18. Brook I, Gober AE. Prophylaxis with amoxicillin or sulfasoxazole for otitis media: effect on the recovery of penicillin-resistant bacteria from children. Clin Infect Dis. 1996;22:143-145. Google Scholar19. Herman S, Roark R. Factors influencing outcome in children treated with antibiotics for acute otitis media. Pediacr Infect Dis J. 1993;12:20-24. Google Scholar20. Doem GV, Brueggemann AB, Pierce G, Hogan T, Holley Jr. HP. Rauch A. Prevalence of antimicrobial resistance among 7Z3 outpatient clinical isolates of Moraxella calormaU! in the United Slates in 1994 and 1995: results of a 30-cemrr national surveillance study. Antimicrob Agents Chemower. 1996;40:2884-2886. Google Scholar21. Rosenfey RM, Vertrees JE, Cart J, Cipolle RJ, Uden DL, Giebink GS, Canafax DM. Clinical efficacy of antimicrobial drugs for acute otitis media: metaanalysis of 5400 children from thirty-three randomiied trials. J Pediatro. 1994;124:355-367. Google Scholar22. Klein JO. Microbiologie efficacy of antibacterial drugs for acute ontis media. Pediotr Infect Dis J. 1993;2:973-975. Google Scholar23. Kaleida PH, Cassclbrani ML. Rockette HE. et al. Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial. Pediatrics. 1991;87:466-474. Google Scholar24. Dowell SF, Marcy SM, Phillips WR, Gerber MA, Schwartz B. Otitis media; principles of judicious use of antimicrobial agents. Pediatrics. 1998; 101 (suppl): 165-171. Google Scholar25. Craig WA, Andes D. Pharmacokmetici and pharmacodynamics of antibiotics in otitis media. Pediatr Infect Dis J. 1996;15:Z55-Z59. Google Scholar26. Craig WA. Interrelationship between pharrnacokinetics and pharmacodynamics in determining dosage regimens fot broad -spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995;22:89-96. Google Scholar27. Harrison CJ. Using antibiotic concentrations in middle ear fluid to predict potential clinical efficacy. Pediarr Infect Dis J. 1997;16(suppl2):S12-S16. Google Scholar28. Klein JO. Antibiotic therapy for acute otitis media (AOM): is amoxicillm still the drug of choice? Rep Pediarr Infect Dis. 1991;1:1-2. Google Scholar29. Harrison CJ, Marks Ml, Welch DF. Microbiology of recently treated otitis media compared to previously untreated purulent otitis media. Pediarr Infect Dis. 1985:4:641-646. Google Scholar30. Bodor FF. Conjunctivitis-otit is syndrome. Pediatrici. 1982;69:695-698. Google Scholar31. Thomson KS. Chartrand SA, Sanders CC, Block SL. Trovafloxacin, a new fluroqmnoione with potent activity against Streptococcus pneumoniae. Antimicrob Agents Chemother 1997;41:478-480. Google Scholar32. Hanison CJ, Chartrand SA, Pichichero ME, Microbiologie and clinical aspects of a trial of once daily cefixime compared with twice daily cefaclor for treatment of acure otitis media in infants and children. Pediarr Inject Dis J. 1993; 12:62-69. Google Scholar33. Dagan R, Yagupsky P. Hiss DM, Leiberman A, Leibovitz E. Bactériologie response in acute otitis media (AOM): comparison between aiithromycin (AZ), cefaclot (CEC), and amoxacillin (AMOX). In: Abstracts of the 37th Interscience Conference on AntimrcroEial Agents and Chemotherapy, September, Toronto, 1997 (abstract K-103). Google Scholar34. Dagan R, Abramson O, Leiboviti E, Greenberg D, Lang R. Goshen S. Yagupsly R Leiberman A, Fliss DM. Bactériologie response to oral cephalosporins: are established susceptibility breakpoints appropriate in the case of acute otitis media? J Infect Dis. 1997; 176: 1253-1259. Google Scholar35. Shyu WC, Haddad J, Reilly J, Khan WN, Campbell DA, Tsai Y. Barbhaiya RH. Penetration of celprozil into middle ear fluid of patients with otitis media. Antimicrob Agents Chemother. 1994;38:2210-2212. Google Scholar36. Pichichero ME. McLinn S. Aronovin G, fiddes R, Blumer J, Nelson K, Dashefesky B. Cefprozil treatment of persistent and recurrent acute otitis media. Pediatr Infect Dis J. 1997;16:471-478. Google Scholar37. Neu HC. In vitro activity of a new broad spectrum, beta-lactamase-stable oral cephalosporin. cefljtime. Pediarr Infect Dis J. 1987;6:958-962. Google Scholar38. Harrison CJ, Chanrand SA. Rodríguez W Schwara R. Pollaci J, Thedinget B, Block SL, Hedrick JA. Middle ear effusion concentrations of cefixime during acute otitis media with effusion and otitis media with effusion. Pediatr infect Dis J. 1997; 16:816-817. Google Scholar39. Kumiesi H, Sheiton S. Brown O, Manning S, Nelson JD. Loracarbef concentrations in middle ear fluid. Anomicrob Agents Cnemotner. 1990:34:2030-2031. Google Scholar40. Barry AL, Fuchs PC, Brown SD. Macrolide resistance among Streptococcus pneumoniae and Streptococcus pyogenes isolates from out-patients in the USA. J Antimicrob Cnemother. 1997;40:139-140. Google Scholar41. McCarty JM. Bacterial susceptibility and tympanocentesis in acute otitis media. Pediatr Infect Dis J. 1995;14:S45-S50. Google Scholar42. Howie VM. Eradication of bacterial pathogens from middle ear infections. CIm Infect Dis. 1992;14(Suppl2):209-210. Google Scholar43. Boken DJ, Chartrand SA, Smilh-Moland E, Goering RV. Colonization with penicillin-nonsusceptible Streptococcus pneumoniae in urban and rural child-care centers. Pediatr Infect Dis J. 1996; 15:667-672. Google Scholar44. Appelbaum PC. Epidemiology and in vitro susceptibility of drug-resistant Streptococcus pneimumiae. Pediatr Infect Dis J. 1996; 15:932-939. Google Scholar45. Gudnason TH. Sigurdardottir LY, Kristinsson KG, Kristjansson K, Laxdal TH, One dose ceftriaxone treatment of otitis media caused by multi-resistant pneumococci. In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. New Orleans, September, 1996 (abstract LM24). Google Scholar46. Blumer J. Presented at ceftriaxone workshop on acute otitis media. New York, NY, January, 1998. Google Scholar47. Seikel K, Sheiton S, McCracken GH, Middle Ear Fluid Concentrations of Amoxicillin after Large Dosages in Children with Acute Otitis Media. Pediatric Infectious Disease Journal, July 1997; 16(7):7 10-711. Google Scholar48. Dowell SF, Marcy SM, Phillips WR, Gerber MA, Schwartz B. Otitis media- principles of judicious use of antimicrobial agents. Pediatrics. 1998;101(suppl): 165-171. Google Scholar49. Giebink GS, Meiet JD, Quartey MK, Liebelet CL, Le CT. Immunogenicity and efficacy of Strrpiococciu pneumoniae polysaccharide-prolein conjugate vaccines against homologous and heterologous serotypes in the chinchilla otitis media model. J Infect Dis. 1996;173:119-127. Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited by Komatsu K, Nam D, Lee J, Yoneda G, Yan C and Li J (2020) Vinpocetine Suppresses Streptococcus pneumoniae –Induced Inflammation via Inhibition of ERK1 by CYLD , The Journal of Immunology, 10.4049/jimmunol.1901299, 204:4, (933-942), Online publication date: 15-Feb-2020. Wang W, Komatsu K, Huang Y, Wu J, Zhang W, Lee J, Miyata M, Xu H, Li J and Sun J (2014) CYLD Negatively Regulates Nontypeable Haemophilus influenzae-Induced IL-8 Expression via Phosphatase MKP-1-Dependent Inhibition of ERK, PLoS ONE, 10.1371/journal.pone.0112516, 9:11, (e112516) Wang W, Hyang Lim J and Li J (2012) Synergistic and feedback signaling mechanisms in the regulation of inflammation in respiratory infections, Cellular & Molecular Immunology, 10.1038/cmi.2011.65, 9:2, (131-135), Online publication date: 1-Mar-2012. Oğuz F, Ünüvar E, Süoğlu Y, Erdamar B, Dündar G, Katircioğlu S and Sıdal M (2003) Etiology of acute otitis media in childhood and evaluation of two different protocols of antibiotic therapy: 10 days cefaclor vs. 3 days azitromycin, International Journal of Pediatric Otorhinolaryngology, 10.1016/S0165-5876(02)00360-9, 67:1, (43-51), Online publication date: 1-Jan-2003. Bakaletz L (2014) Otitis Media Polymicrobial Diseases, 10.1128/9781555817947.ch14, (259-298) Fendrick A, Saint S, Brook I, Jacobs M, Pelton S and Sethi S (2001) Diagnosis and treatment of upper respiratory tract infections in the primary care setting, Clinical Therapeutics, 10.1016/S0149-2918(01)80137-5, 23:10, (1683-1706), Online publication date: 1-Oct-2001. Zhanel G, Dueck M, Hoban D, Vercaigne L, Embil J, Gin A and Karlowsky J (2001) Review of Macrolides and Ketolides, Drugs, 10.2165/00003495-200161040-00003, 61:4, (443-498), . Erramouspe J and Heyneman C (2016) Treatment and Prevention of Otitis Media, Annals of Pharmacotherapy, 10.1345/aph.19391, 34:12, (1452-1468), Online publication date: 1-Dec-2000. Mudry A (1999) Controverses autour de l'otite moyenne aiguë, Archives de Pédiatrie, 10.1016/S0929-693X(00)88899-5, 6:12, (1338-1344), Online publication date: 1-Dec-1999. Bennett J and St. Geme J (1999) BACTERIAL RESISTANCE AND ANTIBIOTIC USE IN THE EMERGENCY DEPARTMENT, Pediatric Clinics of North America, 10.1016/S0031-3955(05)70178-4, 46:6, (1125-1143), Online publication date: 1-Dec-1999. Leggiadro R (1998) Antibiotic therapy for otitis media, Seminars in Pediatric Infectious Diseases, 10.1016/S1045-1870(98)80020-4, 9:4, (310-313), Online publication date: 1-Oct-1998. Bauchner H and Philipp B (1998) Reducing Inappropriate Oral Antibiotic Use: A Prescription for Change, Pediatrics, 10.1542/peds.102.1.142, 102:1, (142-144), Online publication date: 1-Jul-1998. 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Objective. To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants. Methods. A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (less than or equal to 35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and similar to 93% received all five scheduled injections. Results. Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups. Conclusions. Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BFD.

Pyomyositis is defined as a local pyogenic abscess of striated muscle. Often referred to as tropical pyomyositis, it has been increasingly reported in temperate climates. The most common etiologic agent is Staphylococcus aureus. We are reporting the first well-documented pediatric case of group C streptococcal pyomyositis. Case. A 4-year-old boy was admitted to the hospital with a 6-day history of left knee pain. He reportedly struck his knee on a toy 1 week before onset of symptoms. He was seen by a physician 5 days before admission at which time a knee radiograph was interpreted as normal. The child developed progressive pain and swelling of the knee, and 1 day before admission he developed fever. On the day of admission he was unable to bear weight on the affected side. No significant travel or exposure history was elicited. On admission to the hospital his temperature was 102.4°F (tympanic). Physical examination showed soft tissue swelling on the anterior aspect of the lower thigh, superior to the left knee, with palpable effusion of the left knee joint. No overlying wound or superficial cellulitis was present. Considerable pain was present with any movement of the knee which the child held at 90 degrees of flexion. The admission peripheral white blood cell count was 25 200/mm3 with 79% segmented neutrophils, 4% band forms, 11% lymphocytes, 5% monocytes and platelet count 649 000/mm3. The erythrocyte sedimentation rate was 57 mm/h and the C-reactive protein was 16 mg/dl (normal, ≤0.8 mg/dl). A radiograph of the knee demonstrated soft tissue edema and joint effusion. A knee joint aspirate revealed straw-colored fluid containing 27 333 white blood cells/mm3 with 85% neutrophils, 10% lymphocytes and 5% monocytes. The Gram-stained smear showed 40 segmented neutrophils/high power field and no organisms. Glucose concentration was <20 mg/dl. Culture of the joint fluid grew group C Streptococcus (Streptex®; Murex, Dartford, England) susceptible to penicillin (MIC 0.007 μg/ml, MBC 0.007 μg/ml by macrobroth tube dilution). The organism was trehalose-positive and was speciated as Streptococcus equisimilis.1 Blood cultures were sterile. The child was treated initially with intravenous nafcillin, but therapy was changed to penicillin (350 000 units/kg/day) when the culture result became available. He was afebrile by the second hospital day, but tenderness and swelling of the knee and distal thigh persisted. On Hospital Day 6 magnetic resonance imaging (MRI) of the left leg revealed increased T2-weighted signal intensity along the vastus intermedius and vastus lateralis muscles with accompanying contrast enhancement (Fig. 1). There were low density areas in the vastus medialis muscle. On Hospital Day 7 he underwent surgical drainage of the fluid collections. At the time of surgery, a grape-sized mass of solid yellow-white tissue was visualized which extended proximally within the vastus medialis muscle. This was debrided and the wound was irrigated with bacitracin-containing saline. Gram-stained smear of a muscle biopsy specimen showed no white blood cells or organisms. Gram-stained smear of the synovial fluid showed >100 white blood cells/high power field with no organisms. All cultures obtained at the time of surgery were sterile. Microscopic examination of biopsy material revealed necrotic muscle tissue with areas of neutrophil infiltration, liquefaction and microabscess formation. There was gradual clinical improvement during the ensuing 3 days and the patient was discharged home to complete 21 days of intravenous penicillin therapy. The patient was doing well 6 weeks later with normal range of motion of the knee joint. His gait was somewhat stiff on the left and was presumed to be caused by quadriceps weakness. The patient was lost to further follow-up.Fig. 1: Sagittal views of the patient's left thigh showing low density areas in the vastus medialis muscle on T1-weighted images.Discussion. Pyomyositis is a bacterial infection of deep striated muscle, occurring in single or multiple abscess sites. The name "tropical pyomyositis" is used because most cases occur in warm climates. The disease was first reported in North America by Levin et al.2 in 1971 and many cases of "nontropical" pyomyositis have subsequently been reported, mainly in the southwestern states.3, 4 In a 1992 review of North American cases, only 9% of patients had a history of recent travel to tropical climates.4 Males are more commonly affected than females in both temperate (73%) and tropical (78%) climates and 35 (37%) of 95 North American patients were <16 years of age.4 The thigh is the most commonly affected site. More than 50% of patients reported suffered trauma to the affected site. This may predispose muscle tissue to infection and abscess formation during a subsequent and otherwise benign bacteremia. Lower rates of preceding trauma were reported by Gomez-Reino et al.5 (10%) and Patel et al.6 (23%). The majority of these patients were adults with underlying disease. Symptoms of pyomyositis are often insidious, starting with pain and low grade fever and progressing to abscess formation in the later suppurative phase.7 The erythrocyte sedimentation rate is often elevated but muscle isoenzymes may be normal.4 Early diagnosis can be difficult and patients are often admitted with alternative diagnoses, such as cellulitis or septic arthritis.8, 9 Computed tomography and MRI are the most useful diagnostic tests. Although antimicrobial therapy alone has been successful in a few cases, concomitant surgical drainage or computed tomography-guided needle aspiration is required for most patients.4 Pyomyositis is most commonly caused by S. aureus (70 to 90%).4 Group A Streptococcus is the second most common etiologic agent4, 10; cases caused by Gram-negative organisms are rare.4 The only previously reported case of pyomyositis caused by group C streptococci was in a 41-year-old HIV-infected patient with an abscess of the left buttock.11 An 11-year-old patient from Texas developed a thigh pyomyositis secondary to Streptococcus anginosus constellatus,3 and pyomyositis caused by Streptococcus intermedius was reported in Oregon.6 These species of streptococci can also carry the group C Lancefield antigen; however, this information on the patients was not available.12-14 Group C streptococci include any streptococcal species carrying the group C Lancefield antigen. This includes Streptococcus equisimilis, Streptococcus zooepidemicus, Streptococcus equi and Streptococcus dysgalactiae. The latter three are more commonly found in animals and are common veterinary pathogens.12 Small colonies of Streptococcus anginosus (included in Streptococcus milleri group) can also carry the group C streptococcal antigen.12 These bacteria as well as Streptococcus equisimilis are normal inhabitants of the human genital tract, nasopharynx and skin.1 Invasive disease including endocarditis and meningitis caused by group C streptococci has been reported in children.12 The majority of group C streptococci are susceptible to penicillin. In vitro penicillin tolerance with MBC > 32 times the MIC has been reported,15 and some experts recommend combination treatment with a beta-lactam agent plus an aminoglycoside.12, 15 The isolate in this case did not exhibit tolerance, and our patient responded well to high dose penicillin once surgical drainage was achieved. This case represents the first pediatric case of pyomyositis caused by a documented group C Streptococcus. We suspect our patient had a subclinical bacteremia and his prior injury predisposed the affected area to infection. Although cultures obtained from the muscle were sterile, the patient had been treated with antibiotics for 7 days. We believe the pyomyositis was caused by the same group C streptococcus cultured from the knee fluid. Although the joint effusion and muscle abscess were in close proximity on the MRI scan, a direct connection between the two was not found during surgery. Also the joint effusion did not appear to be decompressed into muscle. We presume therefore that there was independent seeding of the joint cavity and muscle. Pyomyositis should be included in the differential diagnosis for pediatric patients with fever and localized deep soft tissue pain, even in nontropical climates. Diagnostic imaging with computed tomography or MRI is often necessary for appropriate diagnosis, and surgical drainage in most cases is necessary for cure. Pyomyositis may be caused by organisms other than S. aureus and culture of the involved site may be crucial for appropriate antibiotic therapy. MIC and MBC determinations should be obtained for group C streptococcal infections since tolerance to penicillin has been reported. Initial empiric therapy for suspected pyomyositis should include a beta-lactamase-stable penicillin or cephalosporin to cover S. aureus and group A streptococci. Alice Pong, M.D. Stephen A. Chartrand, M.D. Walter Huurman, M.D. Departments of Pediatrics and Medical Microbiology; Creighton University School of Medicine (AP, SAC) Department of Orthopedic Surgery; University of Nebraska Medical Center (WH) Omaha, NE

To evaluate whether increased doses of amoxicillin should be used to treat acute pneumococcal otitis media, an in vitro pharmacokinetic model was used to evaluate the killing of pneumococci by amoxicillin when middle ear pharmacokinetics were simulated. Logarithmic-phase cultures were exposed to peak concentrations of 3, 6, and 9 microg of amoxicillin per ml every 12 h, and an elimination half-life of 1.6 h was simulated. Changes in viable bacterial counts were measured over 36 h. All three doses rapidly decreased the viable bacterial counts of penicillin-susceptible strains below the 10-CFU/ml limit of detection by 6 to 10 h and maintained counts below this limit through 36 h. The 3-microg/ml peak dose was much less effective against two of three strains with intermediate penicillin resistance and all three penicillin-resistant strains, with bacterial counts approaching those in drug-free control cultures by 12 h. The 6-microg/ml peak dose completely eliminated two of three strains with intermediate penicillin resistance and maintained viable counts of the other nonsusceptible strains at 1.5 to 2 logs below the initial inoculum through 36 h. The 9-microg/ml peak dose was most effective, completely eliminating all three strains with intermediate penicillin resistance and maintaining the viable counts of the resistant strains at 3 to 4 logs below the original inoculum. The pharmacodynamics observed in this study suggest that peak concentrations of amoxicillin of 6 to 9 microg/ml may be sufficient for the elimination of penicillin-nonsusceptible pneumococcal strains causing otitis media, especially those with intermediate resistance to amoxicillin. In vivo pharmacokinetic studies are needed to determine if these levels can be achieved in middle ear fluid with amoxicillin at 70 to 90 mg/kg/day divided into two daily doses. If these levels are reliably achieved, then clinical studies are warranted.

Anaerobic meningitis is rare in immunocompetent children unless there is a predisposing condition such as a neurenteric fistula.1 The exception to this rule is Fusobacterium necrophorum, a Gram-negative rod that is part of the normal upper respiratory tract flora. This organism can cause meningitis in previously healthy children with significant morbidity and neurologic sequelae.2 One of the major complications of infection with this organism is thrombosis.3 We report a case of an infant with fulminant meningitis in which thrombosis of cerebral vessels both clinically and pathologically played an important role in the brain injury that lead to his demise. Case report. The patient was a 9-month-old previously healthy Caucasian boy who was one of fraternal twins. After a 2-day history of fever, cough, congestion and irritability he became less responsive and had a episode of his eyes rolling up and staring off so he was taken to the local emergency room. His temperature was 105°F rectally, his neck was stiff and he was lethargic. A lumbar puncture revealed purulent cerebrospinal fluid with the following values: glucose, <10 mg/dl; protein, >600 mg/dl; white blood cell count, 36 540/cm3 with 79% polymorphonuclear leukocytes, 20% lymphocytes and 1% monocytes; a stained smear showing many polymorphonuclear leukocytes and Gram-negative rods. The cerebrospinal fluid culture grew a Gram-negative rod in the thioglycolate broth only which was subsequently identified biochemically using the RapANA system (Innovative Diagnostic Systems, Norcross, GA) as F. necrophorum. This identification was confirmed by the Centers for Disease Control and Prevention, Atlanta, GA, by gas-liquid chromatography. A head computerized tomography scan showed mild enlargement of the lateral ventricles but was otherwise unremarkable. He was treated intravenously with ampicillin and cefotaxime after which he was given 1.5 mg of dexamethasone. Shortly after his initial doses of antibiotics he had a brief seizure and received one iv dose of lorazepam, after which he was described as more awake, cooing and kicking in the crib. Within 3 h his neurologic status deteriorated dramatically, resulting in his transfer to our hospital. On arrival he was breathing on his own but had no spontaneous movements or response to voice. The anterior fontanel was concave with no suture diastasis. The pupils were unequal and unresponsive to light. Doll's eyes reflex was absent. There was no facial grimace or gag response. With stimulation the upper extremities assumed the decorticate position and the lower extremities withdrew. He had bilateral hyperreflexia, bilateral ankle clonus and bilateral Babinski signs. An electroencephalogram showed diffuse slowing for age without focal features or epileptiform activity. A head computerized tomography scan done 6 h after his acute neurologic deterioration showed areas of decreased density consistent with infarction in the posterior half of the right thalamus, the left caudate, internal capsule, lentiform nuclei and portions of the left thalamus. The lateral ventricles were slightly larger then they were on the scan done 12 h earlier. There were no areas of enhancement and cortical perfusion appeared normal. Because of his acute deterioration and with the ventricles being somewhat larger on the follow-up scan, a ventricular tap with pressure measurement was performed. A ventriculostomy was placed and ventricular pressure was measured in the 10- to 17-mm Hg range. Analysis of the ventricular cerebrospinal fluid showed: glucose, 70 mg/dl; protein, 147 mg/dl; white blood cell count, 161 cm3 with 76% polymorphonuclear leukocytes, 2% lymphocytes and 22% monocytes. Stained smear revealed Gram-negative rods but the culture was sterile. A trial of mannitol therapy had no benefit and metronidazole was added to the antibiotic regimen. The next morning he developed diabetes insipidus still without elevated ventricular pressure. That evening (now 48 h after presentation) the patient had two brief seizures and the ventricular pressure increased to 20 to 25 mm Hg associated with cardiovascular instability. During the next 48 h intracranial pressure increased to the 30- to 40 mm Hg range and the patient's neurologic examination became consistent with brain death. An electroencephalogram showed absence of electrocerebral activity and perfusion brain scan showed no cerebral perfusion. On postmortem examination there was extensive thick grayish fibropurulent exudate extending from the dorsal convexities of the brain to the cauda equina. This firm exudate filled the subarachnoid space, encasing the cranial nerves and blood vessels and the pituitary within the sella turcica. There was no evidence of communication between the sinuses, middle ear or oropharyngeal cavity and the intracranial vault or of a defect at the spinal cord level. Thrombi were noted in multiple vessels with ischemic infarcts noted including areas of the cortex, basal ganglia, thalamus, hypothalamus, pons, cerebellum, dorsal medulla and spinal cord. The brain and spinal cord were edematous but there was no evidence of herniation. Discussion. In children with anaerobic meningitis without brain abscess, two clinical entities can be distinguished.2 The first is the immunocompromised host where the most common organism is Bacteroides spp., especially Bacteroides fragilis. In contrast anaerobic meningitis in a previously healthy child, often after an upper respiratory infection or otitis media, is most frequently caused by F. necrophorum. These children can have a rapid fulminant course with a poor outcome.2 Historically human F. necrophorum infection has been characterized by a sore throat, sepsis and metastatic abscesses of the lungs or joints.4 This was first described by Lemierre and is now known as necrobacillosis.5 One of the well-known complications of necrobacillosis is septic thrombophlebitis of the internal jugular vein.3 There are also reports documenting thrombotic complications of intracranial vessels in F. necrophorum infections. These have been in the form of cortical vein, venous sinus and arterial thromboses.6-8 The early rapid neurologic deterioration in our patient suggested a primary vascular ischemic event followed later by cerebral edema and increased intracranial pressure as a result of the ischemia. Neuroimaging studies and autopsy findings support this interpretation. There are two cases in the literature that also report infarction as a complication of meningitis caused by this organism.9, 10 The first case was a 23-month-old child whose computerized tomography scan findings showed left parietal lobe, caudate nucleus and bifrontal infarctions.9 The second case was a 5-year-old girl whose autopsy showed extensive purulent leptomeningitis with infarctions in the left internal capsule, mesencephalon, pons and medulla,10 findings very similar to our case. F. necrophorum produces endotoxin and exotoxins such as leukocidin, hemolysin, lipase and cytoplasmic toxin.10 It also produces coagulase that encourages clot formation.7 These toxins may be the cause of the clinical complication of thrombosis that is associated with the organism.11 Treatment with dexamethasone as well as antibiotics did not prevent the vascular complications that resulted in our patient's death. Paul D. Larsen, M.D. Stephen A. Chartrand, M.D. Edward D. Adickes, D.O. Departments of Neurology (PDL, EDA), Pediatrics (PDL, SAC) and Pathology (EDA); Creighton University Medical Center; Omaha, NE

Cefixime is an oral cephalosporin with in vitro activity against Gram-positive and Gram-negative bacteria, including those pathogens commonly associated with acute otitis media with effusion (AOME), and otitis media with effusion (OME) in children. The MIC90 values for cefixime vs. penicillin (PCN)-susceptible Streptococcus pneumoniae, Haemophilus influenzae (whether beta-lactamase-producing or not), and beta-lactamase-producing Moraxella catarrhalis are 0.25, 0.06 and 0.50 mg/l, respectively.1 Concentrations needed to inhibit PCN-resistant pneumococci are >8 mg/l. Mean peak serum concentrations of cefixime occur 4 to 5 h post dosing and following a single oral dose of 8 mg/kg (the recommended dose for treating AOME) are reported to be 3.4 to 3.9 mg/l with an elimination phase half-life (t1/2 beta) of 3 to 4 h. Cefixime is considered to be an effective agent for treatment of AOM in pediatric patients, particularly when beta-lactamase-producing H. influenzae and M. catarrhalis are present.2, 3 However, there are no published data on middle ear fluid (MEE) concentrations of cefixime in children with either AOME or OME. The objective of this study was to compare serum concentrations to MEE concentrations of cefixime during AOME or OME. Methods. Subjects were enrolled by informed consent under a protocol approved by the Institutional Review Board at Creighton University and consisted of otherwise healthy patients 3 months to 5 years of age with either AOME (Bardstown, KY site or Washington DC site) or OME requiring tympanostomy tube placement (Omaha Children's Hospital site). MEE was obtained by tympanocentesis of AOME as previously described1, 4 or before placement of tympanostomy tubes while receiving general anesthesia. Participants were randomly assigned to have MEE fluid samples obtained at 3, 4 or 5 h after a single 8-mg/kg cefixime oral dose. Enrollees had not received other antimicrobials in the previous 48 h. Diagnostic criteria for AOME and OME were previously described.2 Briefly, subjects with AOME had: (1) at least one clinical symptom (fever >101.0°F, pulling at the ears, otalgia or fussiness/irritability); (2) abnormal otoscopic examination (tympanic membrane (TM) inflammation plus bulging or loss of landmarks); (3) decreased mobility on positive and negative insufflation during pneumatic otoscopy; plus (4) an abnormal tympanogram. Criteria for diagnosis of OME required: (1) evidence of middle ear fluid (visible meniscus or limited TM mobility on positive insufflation during pneumatic otoscopy); (2) absence of signs of acute inflammation, TM retraction or absence of TM bulging; and (3) type B or C tympanograms. Subjects were excluded for known hypersensitivity to any beta-lactam antimicrobial, for vomiting or for diarrhea defined as three or more loose/watery stools in the previous 12 h. For AOME subjects a study nurse administered a single 8-mg/kg dose of oral cefixime suspension (20 mg/ml) in the clinic/office. In OME subjects a form was used by parents to document the time of the parent-administered 8-mg/kg dose of cefixime at home before surgery. Tympanocentesis was performed under direct visualization as previously described1, 4 after clearing the external auditory canal of cerumen. When both middle ear spaces in the same child were determined to contain fluid, MEE were obtained from both ears of that child. MEE sample handling. Samples with any visible signs of blood in the trap were not considered valid specimens and were not used. To provide a consistently workable volume of material for centrifugation and to prevent congealing of the specimen, 0.25 ml of saline/dithiothreitol was added to the aspirated specimen. MEE sample volumes were weighed. Specimens, agitated to create a uniform suspension, were placed on ice followed by centrifugation (3900 × g) to remove inflammatory debris. The supernatant was removed and frozen at −20°C. The specimens were kept frozen until shipped overnight on dry ice to the Omaha Creighton site for bioassay. Specimens obtained in Omaha were hand-carried to the Creighton research laboratory on ice for processing. The exact time of middle ear sampling and centrifuging were documented. Blood sample handling. A 5.0 ml sample of blood was obtained within 10 min of MEE sampling. The blood was allowed to clot and was placed on ice followed by centrifugation. Serum was frozen at −20°C until shipped from non-Omaha sites or kept frozen at −70°C at the Omaha Creighton site until assayed. Cefixime bioassay was performed as a modification of a previously reported assay.5 In preliminary experiments with spiked MEE samples, relative error was <10% and addition of dithiothreitol did not affect the cefixime concentration in our bioassay. Bioassay plates were prepared from 100 ml of trypticase soy broth plus purified agar (1.4%), using Providencia ruttgerii ATCC 35565, grown for 18 h at 35°C in trypticase soy broth shaking cultures. Sera diluted in phosphate-buffered saline (1:2) were compared with cefixime standards diluted in 50% normal serum-50% phosphate-buffered saline. MEE diluted with 0.25 ml of wash (9 parts normal saline and 1 part 6.5 mM dithiothreitol (Stat-Pack Sputolysin®; Behring Diagnostics Inc., Somerville, NJ) diluted in phosphate-buffered saline) were compared with cefixime standards in this same buffer. After 18 h of incubation at 35°C, zone sizes of standards around triplicates of 2-fold dilutions in 6-mm discs were plotted to create the standard curve for serum and for MEE spiked with known concentrations of cefixime (16 to 0.03 mg/l). Experimental sample zone sizes were read against the regression line from 0.03 to 4 mg/l standards. Serum and MEE from control (no cefixime administered before tympanocentesis) patients were handled in a fashion identical with that for cefixime patients as bioassay controls. Results.Subjects. Twenty AOME and 27 OME subjects were enrolled. One OME subject was not included when his mother inadvertently administered 4 times the prescribed dose. No adverse effects were noted from the dose. His 3-h serum concentration was 10.7 mg/l and concomitant MEE concentration was 5.69 mg/l. Thirteen MEEs from 12 OME subjects and 6 MEEs from 4 AOME subjects were not analyzed because of blood contamination or inadvertent inadequate freezing of specimen. There were 3 AOME and 4 OME subjects with insufficient sample for assay. There remained 16 assayable MEEs from 13 subjects in the AOME group and 13 assayable MEEs from 10 subjects in the OME group. Subjects were 1.7 ± 1.5 years of age in the AOME group and 3.9 ± 2.2 years of age for the OME group. Mean subject weights were 12.1 ± 4.6 kg in the AOME group and 17.2 ± 6.3 kg in the OME group. Cefixime penetration into MEE during AOME. Overall serum concentrations averaged 2.51 ± 0.79 mg/l and MEE concentrations averaged 1.32 ± 0.85 mg/l in 16 specimens for an overall MEE/serum penetration of 52.8%. (Fig. 1, top). Variability was greater among MEE than among serum concentrations for individual AOME specimens. In 3 subjects in whom both ears were sampled, MEE concentrations varied up to 50% (data not shown).Fig. 1: Individual cefixime concentrations in the right (R) or left (L) middle ear fluid (ME) and serum by time of sampling after oral dosing with 8 mg/kg of cefixime suspension. Top, data from patients with AOME; bottom, patients with OME. Mean concentrations for serum and MEE in AOME were 2.51 ± 0.79 and 1.32 ± 0.85 mg/l, respectively, and for OME concentrations were 3.21 ± 1.09 and 1.40 ± 1.0 mg/l, respectively.Cefixime penetration to MEE during OME. Overall serum concentrations averaged 3.21 ± 1.09 mg/l and MEE concentrations averaged 1.40 ± 1.0 mg/ml in 13 evaluable precentrifuged specimens for an overall MEE/serum penetration of 44%. (Fig. 1. bottom). There was considerable variability among MEE and serum concentrations for individual OME specimens. Discussion. A reasonable goal in treating AOME is for cephalosporin concentrations in the MEE to exceed the MIC90 for each likely pathogen for >50% of the dosing interval; however, studies to confirm achieving this goal would be exceedingly difficult. All MEE in our evaluation contained sufficient cefixime to exceed the MIC90 for nontypable H. influenzae, both beta-lactamase producers and non-producers at the time of assay. Twelve of 16 AOME MEE specimens and 12 of 13 OME MEE specimens contained ≥0.5 mg/l bioactive cefixime (the MIC90 for M. catarrhalis and PCN-susceptible pneumococci). Thus our data indicate that the mean cefixime concentration in MEE during AOME exceeded the MIC90 for common middle ear pathogens except for PCN-resistant pneumococci, although individual subject variation was observed. Variation in penetration also occurred between the right and left ear in the same subject. Overall the percentage penetration of cefixime into MEE was less for OME than for AOME. This may reflect skewing of the data because of the relatively small number of samples. Or it may be a reflection of the fact that serum cefixime concentrations were lower in AOME patients than in OME patients at comparable times after dosing, in view of the absolute MEE cefixime concentrations being fairly similar in AOME and OME. The lower serum concentrations in AOME subjects may be a result of less absorption because of the younger mean age of the subjects or perhaps of the effect of more acute systemic illness on absorption. The higher drug concentrations observed in the one subject not included in analysis because of an excessive dose of cefixime suggest that the 8-mg/kg recommended dose could be increased with at least some concomitant increase in serum and MEE cefixime concentrations. Acknowledgments. This work was funded in part by Wyeth-Lederle Vaccines and Pediatrics Inc. Presented in part at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, FL, October 4 to 7, 1994. Christopher J. Harrison, M.D. Stephen A. Chartrand, M.D. William Rodriguez, M.D. Richard Schwartz, M.D. Jay Pollack, Ph.D. Britt Thedinger, M.D. Stan L. Block, M.D. James A. Hedrick, M.D. Creighton University; Omaha, NE (CJH, SAC, JP, BT) Children's National Medical Center; Washington, DC (WR, RS) Kentucky Pediatric Research; Bardstown, KY (SLB, JAH)

An in vitro study of the activity of 15 antibacterial agents against 202 recent pediatric isolates of Streptococcus pneumoniae from urban and rural Nebraska and rural Kentucky identified trovafloxacin, ofloxacin, clindamycin, and vancomycin as the most active agents and equally active against both penicillin-susceptible and--resistant strains. In contrast, six beta-lactams, three macrolides, and trimethoprim-sulfamethoxazole were less active overall, especially against penicillin-intermediate and--resistant strains. Trovafloxacin inhibited all strains at a concentration of < or = 0.25 micrograms/ml and was 8- to 16-fold more potent than ofloxacin or ciprofloxacin.

Objective. To determine the safety and efficacy of monthly prophylaxis with respiratory syncytial virus immune globulin, intravenous (RSV-IGIV) for reduction of the incidence of RSV-associated hospitalization.Methods. A randomized, double-blind, placebo-controlled clinical trial was conducted at 54 centers in the United States during the 1994 to 1995 RSV season. A total of 510 children with bronchopulmonary dyspIasia and/or a history of prematurity were randomized to receive either 750 mg/kg RSV-IGIV (n = 250) or placebo (1% albumin; n = 260) intravenously every 30 days. Randomized groups were well balanced at entry for demographics, RSV risk factors, and birth characteristics. Children were monitored for adverse events and for RSV-associated hospitalization from randomization through 30 days after the last infusion visit; serious adverse events were monitored for an additional 30 days. For children hospitalized with RSV, data were collected regarding the total days of RSV stay, total days of increased oxygen requirement, total days with a moderate or severe lower respiratory tract illness, and frequency and duration of intensive care unit stay and mechanical ventilation. Ninety-five percent of participants completed the protocol and 85% received a complete course of infusions.Results. The incidence of RSV hospitalization was reduced by 41% in children receiving RSV-IGIV prophylaxis; 35 (13.5%) of the children in the placebo group were hospitalized for RSV, compared with 20 (8.0%) RSV-IGIV recipients. RSV-IGIV recipients had a 53% reduction in the total number of RSV hospital days per 100 children, a 60% reduction in the number of RSV days with increased oxygen requirement, and a 54% reduction in the number of RSV hospital days with a moderate or severe lower respiratory tract illness. In addition, children receiving RSV-IGIV had a 38% reduction in hospitalization for respiratory illness of any cause and a 46% reduction in total hospital days for respiratory illness per 100 children. RSV-IGIV was safe and well tolerated, with a safety profile similar to other IGIV preparations. Between 1% to 3% of children had medically significant adverse events related to RSV-IGIV administration.Conclusions. Monthly administration of 750 mg/kg of RSV-IGIV was safe and well tolerated and was effective in reducing the incidence and total days of both RSV hospitalization and overall respiratory hospitalization in infants with a history of prematurity or bronchopulmonary dysplasia or both.

MEISSNER, H. CODY MD; WELLIVER, ROBERT C. MD; CHARTRAND, STEPHEN A. MD; FULTON, DAVID R. MD; RODRIGUEZ, WILLIAM J. A. MD, PHD; GROOTHUIS, JESSIE R. MD Author Information

OBJECTIVE:To compare the safety and immunogenicity of a one- vs. two-dose regimen of Oka/Merck varicella vaccine in approximately 2000 healthy children 12 months to 12 years of age. METHODOLOGY:Subjects with a negative history of varicella were randomized to receive either one or two injections of the vaccine given 3 months apart and were followed for clinical reactions and serologic response (glycoprotein-based enzyme-linked immunosorbent assay). RESULTS:Both one- and two-dose vaccine regimens were generally well-tolerated. The incidences of varicelliform rash and fever were less frequent after the second injection. However, a slight increase in the incidence of injection site reactions was noted after the second injection; these were generally mild. Seroconversion rates by glycoprotein-based enzyme-linked immunosorbent assay were 98.2% (1700 of 1731) after one injection and 99.9% (717 of 718) after two injections. A significant (P < 0.001) boost in geometric mean titers was observed in children who received a second injection of vaccine 3 months after the first injection. Of the children who seroconverted at 6 weeks postregimen (one or two doses as assigned), 99.8% (528 of 529) of the one-dose group and 99.8% (473 of 474) of the two-dose group maintained antibody to varicella at 1 year with geometric mean titers of 19.5 and 31.2, respectively. CONCLUSIONS:Administration of a one- or two-dose regimen of the live Oka/Merck varicella vaccine (VARIVAX) is immunogenic and is generally well-tolerated in healthy children 1 to 12 years old. Antibody to varicella persists in > 99% of vaccinees 1 year after vaccination regardless of a one- or two-dose regimen. Long-term follow-up studies of this cohort of children may determine whether a two-dose regimen offers superior protection against chickenpox.

OBJECTIVES:To determine the prevalence of penicillin-nonsusceptible Streptococcus pneumoniae (NS-SP) at 12 child-care centers (CCC) in urban and rural Nebraska and to evaluate the genetic diversity of pneumococcal strains present in the CCC environment.METHODS:Nasopharyngeal cultures for S. pneumoniae were obtained from children 2 to 24 months old. Capsular serotyping, pulsed field gel electrophoresis (PFGE) and microbroth dilution MICs were performed for all S. pneumoniae. Antibiotic exposure was also evaluated as a potential risk factor for colonization with NS-SP.RESULTS:Nasopharyngeal colonization with S. pneumoniae was present in 121 (56%) of 215 children. The MICs of penicillin were 0.12 to 1.0 microgram/ml for 57 (47%) and > 1.0 microgram/ml for 10 (8%) isolates. Clindamycin MICs of > 0.5 microgram/ml were found in 6 isolates (5%). MICs of ceftriaxone were 0.5 microgram/ml in 28% of S. pneumoniae and 1.0 microgram/ml in 7%. PFGE and capsular serotyping demonstrated multiple strains that were penicillin-nonsusceptible in both the urban and rural CCC. PFGE and capsular serotype defined shared strains within each CCC, but some PFGE "types" could be found in multiple serotypes. Antibiotic exposure during the 2 months before nasopharyngeal culture was not a statistically significant risk factor for nasopharyngeal colonization with NS-SP.CONCLUSIONS:NS-SP are highly prevalent in urban and rural Nebraska. PFGE similarities between serotypes may reflect "serotype switching" but may also reflect genetic similarity between S. pneumoniae strains.

From January, 1992, to January, 1994, penicillin-resistant (minimal inhibition concentration (MIC) > 0.06 microgram/ml) Streptococcus pneumoniae (PRSP) isolates accounted for 48 (17%) of 283 isolates from acute otitis media (AOM) or recurrent AOM in 246 ambulatory patients in rural Kentucky. By broth microdilution, relatively penicillin-resistant (MIC > 0.06 to 1.0 microgram/ml) and highly penicillin-resistant (MIC > or = 2.0 micrograms/ml) strains were detected in 25 (16%) and 23 (15%), respectively, of 157 pneumococcal middle ear isolates. Using 1994 National Committee for Clinical Laboratory Standards breakpoints for pneumococci (unavailable for oral cephalosporins except cefuroxime), highly PRSP strains were almost uniformly susceptible to clindamycin and vancomycin. In contrast highly PRSP strains were resistant to most oral antimicrobials customarily used for AOM with one-third of strains highly resistant (MIC > or = 2.0 micrograms/ml) to ceftriaxone. Serotypes 6B, 19F and 23F accounted for 95% of highly PRSP strains and serotype 9V for 48% of relatively PRSP strains. By multivariate analysis, otitis-prone condition (P = 0.0008) and number of antibiotic courses before day of culture (P < 0.0001) were independently predictive of PRSP. Highly PRSP isolates were more commonly isolated from patients recently treated within 3 days (30%) vs. those who completed therapy more than 3 days earlier (2%) (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

We obtained nasopharyngeal cultures for Streptococcus pneumoniae from 54 children ages 2 to 24 months attending an Omaha child-care center (CCC) in April 1994. Thirty-two (59%) of the 54 children were colonized with S. pneumoniae belonging to serotypes 23, 19, 6 and 11. Seventeen (53%) of the pneumococcal isolates were highly resistant to penicillin (minimal inhibitory concentration > or = 2.0 micrograms/ml; HR-SP) and 7 (22%) were intermediately resistant to penicillin (0.12 < or = minimal inhibitory concentration < or = 1.0 microgram/ml; IR-SP). Within each pneumococcal capsular serotype, there were 1 to 3 DNA subtypes based on pulsed field gel electrophoresis analysis. A single pulsed field gel electrophoresis strain predominated in most CCC rooms, suggesting horizontal transmission among cohorted children. Nasopharyngeal cultures obtained 4 months later revealed similar S. pneumoniae colonization rates (28 of 52, 54%); however, only 2 (7%) of 28 isolates were HR-SP and 11 (39%) were IR-SP. Colonization with resistant pneumococci persisted after 4 months in 4 (12%) of 34 children cultured on both occasions. Antibiotic use by attendees had decreased notably between the two sampling periods, suggesting that selective pressure within the CCC might contribute to seasonal variation in colonization rates with HR-SP and IR-SP. We conclude that multiple genetic clones of penicillin-resistant pneumococci can occur simultaneously in a single CCC, especially during periods of heavy antibiotic selection pressure. However, individual clones of penicillin-resistant S. pneumoniae may be spread from child to child, suggesting that colonization with penicillin-resistant S. pneumoniae should now be considered a CCC-associated phenomenon.