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Penicillin—Intermediate-resistant pneumococcal spondylodiscitis
ELSEVIER
CASE
REPORT
Penicillin-Intermediate-Resistant Pneumococcal Spondylodiscitis J.A. Arranz-Caso, N. Sol& A. Sanchez-Atrio, and I?. Gomez-Herruz
Pneumococcal osteomyelitis probably was more common in the pre-antibiotic era, but currently is rare. Sickle-cell disease and, possibly, bone trauma and advanced age are predisposing factors for pneumococcal osteomyelitis. Bone infection usually OCCUYS as a result of hematogenous spread from an infective focus, which often cannot be identified. In patients without evidence of other focci of infection, pneumococcal spondylodiscitis probably is caused by ‘prima y” pneumococcal bacteriemia, originating in the oropha ynx, especially if the patient has alterations that disrupt the oropha yngeal mucose.
Whereas early in the antibiotic era, all Streptococcus pneustrains were susceptible to penicillin, resistance to this antibiotic is on the rise, and in many parts of the world, it has emerged as a major problem. We report the case of a young patient with penicillin-resistant pneumococcal vertebral and intervertebral disk disease who had no evidence of pneumococcal infection elsewhere, and we discuss the possible mechanism of infection. We also review briefly the resistance to penicillin of S. pneumoniae and the treatment of choice. 0 1997 Elsevier Science Inc.
INTRODUCTION
CASE
Pneumococcal vertebral and disk disease is rare; in a review by Waldvogel and Vasey in 1980, only one patient out of a total of 348 with vertebral osteomyelitis had pneumococcal infection. Since then, only four cases of pneumococcal vertebral disk disease have been reported in the English-language literature (Gelfand and Miller 1987; Schleiter and Gantz 1986; Gelfand and Cleveland 1992; GarciaZamalloa et al. 1994) (MEDLINE). We report the case of a young patient with penicillin-resistant pneumococcal vertebral and intervertebral disk disease who had no evidence of pneumococcal infection elsewhere.
From the Internal Medicine, Rehumatology fJAA-C, NS, ASA) and Microbiology (PC-H) Departments, Prfncipe de Asturias University Hospital, School of Medicine, University of Alcala de Henares, Madrid, Spain. Address reprint requests to J.A. Arranz-Caso, Servicio de Medicina Interna, Hospital Prmcipe de Asturias, Carretera de Alcal&Meco, s/n 28800 Madrid, Spain. Received 30 May 1996; revised and accepted 31 October 1996.
DIAGN MICROBIOL INFECT DIS 1996;26:137-139 0 1997 Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
moniae
REPORT
The patient was a 15-year-old male with no pertinent medical history except for chronic gum hypertrophy of unknown origin. Approximately 6 weeks before admission, a hyperextensive movement made while playing basketball originated acute lumbar pain, which remitted after a few days of treatment with analgesics. Three weeks later, he had general malaise and fever with chills, which remitted after 5 days of treatment with analgesics. Two days after that, lumbar pain reappeared; it was aggravated by standing, and daily morning fever appeared. In spite of analgesic treatment (acetaminophen, 500 mg/6h), the patient showed no improvement, and he was referred to the hospital. His body temperature was 38.3”C; the physical examination was normal except for moderate generalized gum hypertrophy, areas of gum inflammation, and pain elicited by pressure on the L4 and L5 apophyses. No heart murmur or relevant skin condition was present. Sacroiliac maneuvers found no abnormality, and the Lassege sign was negative; the osteoarticular examination detected no other abnormalities. Hematologic studies showed: leukocytes 8900/dl (no increase in immature forms), Hb
0732~8893/97/$17.00 PI1 SO732-8893(96)00203-9
J.A. Arranz-Caso
138
118 g/l, and erythrocyte sedimentation rate 65 mm in the first hour. Findings were normal or negative for blood determinations of glucose, plasma creatinine, proteins; Ca+, P-, Naf, Kf, Cl-; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactic dehydrogenase; rheumatoid factor; antinuclear antibodies, complement; hepatitis B virus, hepatitis C virus, Brucella, Yersinia, and Shigella serology; Mantoux test; radiography of the chest, lumbar spine, sacroiliac region, and paranasal sinuses; and echocardiography. A technetium-99 and gallium-67 bone scan showed abnormal uptake by the L4, L5 vertebral bodies, and magnetic resonance imaging showed destruction of the L4, L5 disk with involvement of the adjacent regions of L4 and L5 and uptake of paramagnetic contrast at these sites (Figure 1). The spinal cord and roots were unaffected. TCguided lumbar fine-needle biopsy carried out in sterile conditions obtained material that produced a pure culture of Streptococctls pneumonine growth at 48 h. MIC to penicillin, determined by E-test, was 0.75 pLg/
FIGURE 1 Magnetic resonance imag ing showing destruction of the L4, L5 disk with involve :ment of the adjacent regions of L4 and L5 and uptake of paramagnetic contrast.
et al.
ml, and to cefotaxime co.016 kg/ml. Three blood cultures were negative, even after prolonged incubation. Treatment with ceftriaxone was initiated (2 g/day iv for 15 days while hospitalized and 1 g/day im for 15 days after release from the hospital). The patient’s fever and symptoms remitted in the first 3 to 4 days, and by 12 days, the erythrocyte sedimentation rate had decreased to 18 mm/l h. Six months later the patient was well and had a normal hemogram (Hb 13.0 g/dl), an erythrocyte sedimentation rate of 5 mm/l h, and a technetium-gallium bone scan with no abnormal uptake. DISCUSSION Pneumococcal osteomyelitis probably was more common in the pre-antibiotic era (Schleiter and Gantz 1986; Gelfand and Cleveland 1992). Pneumococcal osteomyelitis in any site now is rare. Schleiter and Gantz found only 5 cases of pneumococcal osteomyelitis (only two vertebral) from a total of 401 cases of osteomyelitis compiled in 1962 and 1979. In children, Chusid (1981) renorted a series of 5 cases, none of them vertebral. as
high resistance (Doern et al. 1996). The highest rates of penicillin resistance were noted with pneumococci from pediatric patients, in particular those with sinus and otic infections. In Spain, between 1988 and 1993,
Pneumococcal
139
Spondylodiscitis
20% and 11% of S. pneumoniae isolates of patients with pneumonia, manifested intermediate and high resistance to penicillin respectively (Pallares et al. 1995). Probably, extensive exposure to P-lactams antimicrobial agents results in selective pressure. The mechanism of penicillin resistance is alteration of high molecular weight penicillin-binding proteins. These proteins are necessary, too, for the activity of other p-lactams such as some cephalosporins and carbapenems and also for the activity of p-lactamase inhibitor combinations (Doern et al. 1996). Consequently, some of these agents have lower activity against penicillin-resistant pneumococci. Cephalosporins with high intrinsic activity against such S. pneumoniae penicillin-susceptible strains as cefuroxime, cefpodoxime, cefotaxime, and ceftriaxone can be considered valuable in treating infections caused by intermediate-resistant pneumococci, and only ceftriaxone and cefotaxime are useful in infections with high-resistant pneumococci (Doern et al.). Although high-dose intravenous penicillin is useful for treating pneumonia caused by S. pneumoniae having intermediate penicillin resistance (Musher 1992), penicillin definitely should not be used in cases of meningitis caused by these strains of pneumococci (Friedland and McKraken 1994; Pallares et al. 1995). Of great concern are recent reports of clinical isolates of penicillin-resistant S. pneumoniae with high-level resistance against cefotaxime and ceftriaxone (Doern et al.; Pallares et al.) as well as other strains that are also resistant to such antimicrobial agents as macrolides, tetracycline, chloranphenicol, and trimethoprimsulfamethoxazole (Doern et al.). Among the agents examined in different works, vancomycin is the only compound for which S. pneumoniae is almost uniformly susceptible (Friedland and McKraken; Pallares et al.; Doern et al.). As a
result, third-generation cephalosporins and vancomycin are the antibiotics most frequently used for treating penicillin-resistant pneumococcal infections (Friedland and McKraken). This patient had vertebral disk disease caused by S. pneumoniae and no evidence of pneumococcal infection elsewhere. However, he probably had oropharyngeal S. pneumoniae colonization, and the presence of gingivitis may have favored the occurrence of bacteriemia. The febrile episode preceding the appearance of lumbar pain may have been caused by pneumococcal bacteriemia. Likewise, the patient’s lumbar trauma may have disturbed the richly vascularized flat bone and adjacent cartilage (Waldvogel and Vasey 1980; Gelfand and Miller 1987; Schleiter and Gantz 1986), thus reducing its capacity for eliminating of blood-borne microorganisms and favoring local infection. S. pneumoniae must be blamed in cases of spondylodiscitis, principally in patients with other focci of pneumococcal infection. In patients without evidence of other focci of infection, pneumococcal spondylodicitis probably is caused by “primary” pneumococcal bacteriemia, originating in the oropharynx, especially if the patient has alterations that disrupt the oropharyngeal mucose. Although high-dose intravenous penicillin may be useful in cases of spondylodiscitis by penicillinintermediate resistant S. pneumoniae, treatment with a third-generation cephalosporin is probably preferable. In addition, ceftriaxone has the advantage of reducing the hospital stay because parenteral and outpatient administration of this agent is relatively easy. In cases of high resistance, a complete test of susceptibility must be obtained, and if resistance to third-generations cephalosporins also exists, vancomycin is the treatment of choice.
REFERENCES Chusid MJ, Sty JR (1981) Pneumococcal osteomyelitis 107.
in children.
arthritis and Clin Pediutr (Phila) 20:105-
Doer GV, Brueggemann A, Holley HP, Rauch AM (1996) Antimicrobial resistance of streptococcus pneumoniue recovered from outpatients in the United States during the winter months of 1994 to 1995: Results of a 30-center national surveillance study. Antimicrob Agents Chemother 40:1028-1213. Friedland IR, McKraken JR (1994) Management of infections caused by antibiotic-resistant Streptococcus pneurnoniae. N Engl J Med 331~377-382.
Gelfand MS, Cleveland KO (1992) Penicillin-resistant pneumococcal vertebral osteomyelitis. CID 15:746-747. Musher DM (1992) Infections caused by Streptococcus pneumoniae: Clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis 14:801-809. Pallares R, Liiiares J, Vadillo M, Cabellos C, Manresa F, Viladrich PF, et al. (1995) Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 333:474480. Schleiter G, Gantz NM (1986) Vertebral osteomyelitis secondary to streptococcus pneumoniae: A pathophysiologic understanding. Diagn Microbial Infect Dis 5:77-80.
Garcia-Zamalloa AM, Uribeecheverria E, Urcelay-Zald6a G, and Yerobi-Errondosoro J (1994) Endocarditis subaguda y espondilodiscitis por streptococcus pneumoniae. Med Clin (Bare) 102:797.
Spitalny KC, Bronberg K, Ginsberg MB (1982) Streptococcus pneumoniae bacteriemia without an identificable focus in adults. Johns Hopkins Med J 150:35-37.
Gelfand MS, Miller JH (1987) Pneumococcal vertebral osteomyelitis in an adult. South Med J 80:534-535.
Waldvogel FA, Vasey H (1980) Osteomyelitis: cade. N Engl J Med 303:360-70.
The past de-
CASE
REPORT
Penicillin-Intermediate-Resistant Pneumococcal Spondylodiscitis J.A. Arranz-Caso, N. Sol& A. Sanchez-Atrio, and I?. Gomez-Herruz
Pneumococcal osteomyelitis probably was more common in the pre-antibiotic era, but currently is rare. Sickle-cell disease and, possibly, bone trauma and advanced age are predisposing factors for pneumococcal osteomyelitis. Bone infection usually OCCUYS as a result of hematogenous spread from an infective focus, which often cannot be identified. In patients without evidence of other focci of infection, pneumococcal spondylodiscitis probably is caused by ‘prima y” pneumococcal bacteriemia, originating in the oropha ynx, especially if the patient has alterations that disrupt the oropha yngeal mucose.
Whereas early in the antibiotic era, all Streptococcus pneustrains were susceptible to penicillin, resistance to this antibiotic is on the rise, and in many parts of the world, it has emerged as a major problem. We report the case of a young patient with penicillin-resistant pneumococcal vertebral and intervertebral disk disease who had no evidence of pneumococcal infection elsewhere, and we discuss the possible mechanism of infection. We also review briefly the resistance to penicillin of S. pneumoniae and the treatment of choice. 0 1997 Elsevier Science Inc.
INTRODUCTION
CASE
Pneumococcal vertebral and disk disease is rare; in a review by Waldvogel and Vasey in 1980, only one patient out of a total of 348 with vertebral osteomyelitis had pneumococcal infection. Since then, only four cases of pneumococcal vertebral disk disease have been reported in the English-language literature (Gelfand and Miller 1987; Schleiter and Gantz 1986; Gelfand and Cleveland 1992; GarciaZamalloa et al. 1994) (MEDLINE). We report the case of a young patient with penicillin-resistant pneumococcal vertebral and intervertebral disk disease who had no evidence of pneumococcal infection elsewhere.
From the Internal Medicine, Rehumatology fJAA-C, NS, ASA) and Microbiology (PC-H) Departments, Prfncipe de Asturias University Hospital, School of Medicine, University of Alcala de Henares, Madrid, Spain. Address reprint requests to J.A. Arranz-Caso, Servicio de Medicina Interna, Hospital Prmcipe de Asturias, Carretera de Alcal&Meco, s/n 28800 Madrid, Spain. Received 30 May 1996; revised and accepted 31 October 1996.
DIAGN MICROBIOL INFECT DIS 1996;26:137-139 0 1997 Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
moniae
REPORT
The patient was a 15-year-old male with no pertinent medical history except for chronic gum hypertrophy of unknown origin. Approximately 6 weeks before admission, a hyperextensive movement made while playing basketball originated acute lumbar pain, which remitted after a few days of treatment with analgesics. Three weeks later, he had general malaise and fever with chills, which remitted after 5 days of treatment with analgesics. Two days after that, lumbar pain reappeared; it was aggravated by standing, and daily morning fever appeared. In spite of analgesic treatment (acetaminophen, 500 mg/6h), the patient showed no improvement, and he was referred to the hospital. His body temperature was 38.3”C; the physical examination was normal except for moderate generalized gum hypertrophy, areas of gum inflammation, and pain elicited by pressure on the L4 and L5 apophyses. No heart murmur or relevant skin condition was present. Sacroiliac maneuvers found no abnormality, and the Lassege sign was negative; the osteoarticular examination detected no other abnormalities. Hematologic studies showed: leukocytes 8900/dl (no increase in immature forms), Hb
0732~8893/97/$17.00 PI1 SO732-8893(96)00203-9
J.A. Arranz-Caso
138
118 g/l, and erythrocyte sedimentation rate 65 mm in the first hour. Findings were normal or negative for blood determinations of glucose, plasma creatinine, proteins; Ca+, P-, Naf, Kf, Cl-; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactic dehydrogenase; rheumatoid factor; antinuclear antibodies, complement; hepatitis B virus, hepatitis C virus, Brucella, Yersinia, and Shigella serology; Mantoux test; radiography of the chest, lumbar spine, sacroiliac region, and paranasal sinuses; and echocardiography. A technetium-99 and gallium-67 bone scan showed abnormal uptake by the L4, L5 vertebral bodies, and magnetic resonance imaging showed destruction of the L4, L5 disk with involvement of the adjacent regions of L4 and L5 and uptake of paramagnetic contrast at these sites (Figure 1). The spinal cord and roots were unaffected. TCguided lumbar fine-needle biopsy carried out in sterile conditions obtained material that produced a pure culture of Streptococctls pneumonine growth at 48 h. MIC to penicillin, determined by E-test, was 0.75 pLg/
FIGURE 1 Magnetic resonance imag ing showing destruction of the L4, L5 disk with involve :ment of the adjacent regions of L4 and L5 and uptake of paramagnetic contrast.
et al.
ml, and to cefotaxime co.016 kg/ml. Three blood cultures were negative, even after prolonged incubation. Treatment with ceftriaxone was initiated (2 g/day iv for 15 days while hospitalized and 1 g/day im for 15 days after release from the hospital). The patient’s fever and symptoms remitted in the first 3 to 4 days, and by 12 days, the erythrocyte sedimentation rate had decreased to 18 mm/l h. Six months later the patient was well and had a normal hemogram (Hb 13.0 g/dl), an erythrocyte sedimentation rate of 5 mm/l h, and a technetium-gallium bone scan with no abnormal uptake. DISCUSSION Pneumococcal osteomyelitis probably was more common in the pre-antibiotic era (Schleiter and Gantz 1986; Gelfand and Cleveland 1992). Pneumococcal osteomyelitis in any site now is rare. Schleiter and Gantz found only 5 cases of pneumococcal osteomyelitis (only two vertebral) from a total of 401 cases of osteomyelitis compiled in 1962 and 1979. In children, Chusid (1981) renorted a series of 5 cases, none of them vertebral. as
high resistance (Doern et al. 1996). The highest rates of penicillin resistance were noted with pneumococci from pediatric patients, in particular those with sinus and otic infections. In Spain, between 1988 and 1993,
Pneumococcal
139
Spondylodiscitis
20% and 11% of S. pneumoniae isolates of patients with pneumonia, manifested intermediate and high resistance to penicillin respectively (Pallares et al. 1995). Probably, extensive exposure to P-lactams antimicrobial agents results in selective pressure. The mechanism of penicillin resistance is alteration of high molecular weight penicillin-binding proteins. These proteins are necessary, too, for the activity of other p-lactams such as some cephalosporins and carbapenems and also for the activity of p-lactamase inhibitor combinations (Doern et al. 1996). Consequently, some of these agents have lower activity against penicillin-resistant pneumococci. Cephalosporins with high intrinsic activity against such S. pneumoniae penicillin-susceptible strains as cefuroxime, cefpodoxime, cefotaxime, and ceftriaxone can be considered valuable in treating infections caused by intermediate-resistant pneumococci, and only ceftriaxone and cefotaxime are useful in infections with high-resistant pneumococci (Doern et al.). Although high-dose intravenous penicillin is useful for treating pneumonia caused by S. pneumoniae having intermediate penicillin resistance (Musher 1992), penicillin definitely should not be used in cases of meningitis caused by these strains of pneumococci (Friedland and McKraken 1994; Pallares et al. 1995). Of great concern are recent reports of clinical isolates of penicillin-resistant S. pneumoniae with high-level resistance against cefotaxime and ceftriaxone (Doern et al.; Pallares et al.) as well as other strains that are also resistant to such antimicrobial agents as macrolides, tetracycline, chloranphenicol, and trimethoprimsulfamethoxazole (Doern et al.). Among the agents examined in different works, vancomycin is the only compound for which S. pneumoniae is almost uniformly susceptible (Friedland and McKraken; Pallares et al.; Doern et al.). As a
result, third-generation cephalosporins and vancomycin are the antibiotics most frequently used for treating penicillin-resistant pneumococcal infections (Friedland and McKraken). This patient had vertebral disk disease caused by S. pneumoniae and no evidence of pneumococcal infection elsewhere. However, he probably had oropharyngeal S. pneumoniae colonization, and the presence of gingivitis may have favored the occurrence of bacteriemia. The febrile episode preceding the appearance of lumbar pain may have been caused by pneumococcal bacteriemia. Likewise, the patient’s lumbar trauma may have disturbed the richly vascularized flat bone and adjacent cartilage (Waldvogel and Vasey 1980; Gelfand and Miller 1987; Schleiter and Gantz 1986), thus reducing its capacity for eliminating of blood-borne microorganisms and favoring local infection. S. pneumoniae must be blamed in cases of spondylodiscitis, principally in patients with other focci of pneumococcal infection. In patients without evidence of other focci of infection, pneumococcal spondylodicitis probably is caused by “primary” pneumococcal bacteriemia, originating in the oropharynx, especially if the patient has alterations that disrupt the oropharyngeal mucose. Although high-dose intravenous penicillin may be useful in cases of spondylodiscitis by penicillinintermediate resistant S. pneumoniae, treatment with a third-generation cephalosporin is probably preferable. In addition, ceftriaxone has the advantage of reducing the hospital stay because parenteral and outpatient administration of this agent is relatively easy. In cases of high resistance, a complete test of susceptibility must be obtained, and if resistance to third-generations cephalosporins also exists, vancomycin is the treatment of choice.
REFERENCES Chusid MJ, Sty JR (1981) Pneumococcal osteomyelitis 107.
in children.
arthritis and Clin Pediutr (Phila) 20:105-
Doer GV, Brueggemann A, Holley HP, Rauch AM (1996) Antimicrobial resistance of streptococcus pneumoniue recovered from outpatients in the United States during the winter months of 1994 to 1995: Results of a 30-center national surveillance study. Antimicrob Agents Chemother 40:1028-1213. Friedland IR, McKraken JR (1994) Management of infections caused by antibiotic-resistant Streptococcus pneurnoniae. N Engl J Med 331~377-382.
Gelfand MS, Cleveland KO (1992) Penicillin-resistant pneumococcal vertebral osteomyelitis. CID 15:746-747. Musher DM (1992) Infections caused by Streptococcus pneumoniae: Clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis 14:801-809. Pallares R, Liiiares J, Vadillo M, Cabellos C, Manresa F, Viladrich PF, et al. (1995) Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 333:474480. Schleiter G, Gantz NM (1986) Vertebral osteomyelitis secondary to streptococcus pneumoniae: A pathophysiologic understanding. Diagn Microbial Infect Dis 5:77-80.
Garcia-Zamalloa AM, Uribeecheverria E, Urcelay-Zald6a G, and Yerobi-Errondosoro J (1994) Endocarditis subaguda y espondilodiscitis por streptococcus pneumoniae. Med Clin (Bare) 102:797.
Spitalny KC, Bronberg K, Ginsberg MB (1982) Streptococcus pneumoniae bacteriemia without an identificable focus in adults. Johns Hopkins Med J 150:35-37.
Gelfand MS, Miller JH (1987) Pneumococcal vertebral osteomyelitis in an adult. South Med J 80:534-535.
Waldvogel FA, Vasey H (1980) Osteomyelitis: cade. N Engl J Med 303:360-70.
The past de-