Published online April 10, 2006
PEDIATRICS Vol. 117 No. 5 May 2006, pp. e1061-e1066 (doi:10.1542/peds.2005-1994)
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EXPERIENCE & REASON

Pneumonia and Empyema Caused by Penicillin-Resistant Neisseria meningitidis: A Case Report and Literature Review

Daniel Glikman, MDa, Scott M. Matushek, MSb, Madelyn D. Kahana, MDc and Robert S. Daum, MDa

a Department of Pediatrics, Sections of Infectious Diseases
c Critical Care, University of Chicago, Chicago, Illinois
b Clinical Microbiology Laboratories, University of Chicago Hospitals, Chicago, Illinois

ABSTRACT

Pneumonia is an uncommon manifestation of Neisseria meningitidis infection, and empyema is rarely reported. Uniform penicillin susceptibility has been assumed for meningococcal infections for many years, but decreased penicillin susceptibility has been recognized recently with increasing frequency. Breakpoints to define different categories of susceptibility were published recently by the Clinical and Laboratory Standards Institute. We report the case of a teenage girl with sepsis and extensive bilateral pneumonia with empyema caused by an N meningitidis isolate that was resistant to penicillin. Her protracted clinical course suggested that penicillin resistance contributed to her delayed recovery. Our experience with this patient suggests that susceptibility testing should be performed in every case of N meningitidis isolation, and treatment with a third-generation cephalosporin should be provided until the susceptibility results are known. Clinical suspicion of N meningitidis as a possible cause of respiratory symptoms accompanied by hypotension, even in the absence of a rash, may aid in diagnosis and therefore in the treatment and provision of prophylaxis to contacts of patients with meningococcal disease.

Key Words: Neisseria meningitidis • pneumonia • empyema • penicillin resistance

Abbreviations: CLSI, Clinical and Laboratory Standards Institute • CT, computed tomography • MIC, minimal inhibitory concentration • CDC, Centers for Disease Control and Prevention

Invasive meningococcal disease first was described by Vieusseux in Geneva 200 years ago1 and remains an important cause of sepsis and meningitis worldwide. Approximately 3000 cases are said to occur each year in the United States. Almost all are sporadic, although epidemics of meningococcal disease are common in sub-Saharan Africa.2

Meningococcal pneumonia can be a solitary infectious focus or can be accompanied by meningococcemia or meningitis. Blood or pleural cultures that yield Neisseria meningitidis establish the diagnosis with certainty. In a recent review by Winstead et al,3 only 58 cases of meningococcal pneumonia were reported in 1974–1998. Empyema is a rarely reported complication.

Penicillin G was for many years the drug of choice for the treatment of meningococcal infections. However, emergence of strains with decreased susceptibility to penicillin has been reported from several countries. In Spain, up to 55% of isolates had decreased susceptibility to penicillin.4 The prevalence of decreased susceptibility to penicillin in the United States has remained low, did not change in 1991–1997,5 but now may be increasing.6 Strains with decreased susceptibility to penicillin have been referred to variously as relatively penicillin-resistant, moderately penicillin-susceptible, or of diminished susceptibility to penicillin, but breakpoints to define different categories of susceptibility were not published until recently.7,8

We recently cared for a teenager from Chicago with meningococcal sepsis, extensive bilateral pneumonia, and large empyema caused by a penicillin-resistant N meningitidis isolate. It is the first report of a correlation between laboratory and clinical penicillin resistance in an N meningitidis isolate from the United States since resistance was defined by the Clinical and Laboratory Standards Institute (CLSI).

CASE REPORT

A 14-year-old black girl sought medical care for left-sided chest pain and difficulty in breathing that began 1 day before admission. She had been healthy until 4 days before admission, when sore throat, rhinorrhea, mild cough, and muscle pain developed associated with tactile warmth. Her past medical history and family history were noncontributory.

On physical examination, she appeared ill with respiratory distress. The respiratory rate was 60 per minute, the heart rate was 120 beats per minute, the temperature was 35.3°C, and the blood oxygen saturation was 88% in room air. The blood pressure was not measurable, and multiple fluid boluses of normal saline were administered, after which the blood pressure was 100/36 mm Hg. The heart sounds were normal. On chest auscultation, coarse sounds with crackles over both bases were heard. The abdomen was soft without hepatosplenomegaly; the extremities were cool with weak peripheral pulses. Signs of meningeal irritation, pharyngitis, rash, or muscle tenderness were absent.

Laboratory evaluation revealed the C-reactive protein to be 313 mg/L (reference: <5 mg/L). The leukocyte count was 1300 cells/mm3 with 20% neutrophils, 35% bands, 24% lymphocytes, and 18% monocytes. The hemoglobin was 13.3 g/dL, and the platelets were 243 x 103/mm3. The venous pH was 7.18, the PCO2 was 48 mm/Hg, and the base excess was –11. The lactate concentration was 52 mg/dL. The international normalization ratio was 2.0, the partial thromboplastin time was 42 seconds, and the D-dimer level was 2.16 µg/mL (reference: <0.42 µg/mL). The creatine phosphokinase was 207 U/L, the serum creatinine was 1.2 mg/dL, and the serum urea nitrogen was 29 mg/dL. The total protein was 5 g/dL. The aspartate aminotransferase was 50 U/L, and the alanine aminotransferase was 42 U/L. The total bilirubin was 0.6 mg/dL, and the alkaline phosphatase was 70 U/L. The urinalysis was normal. A chest film showed extensive left lower lobe and segmental right lower and right upper lobe consolidations without pleural effusion.

She was transferred to the PICU, where the systolic arterial blood pressure was 60 mm Hg. She received additional intravenous fluids, inotropic support, oxygen supplementation, and a single dose of intravenous immunoglobulin. Vancomycin, ceftriaxone, clindamycin, and gentamicin were administered.

The clinical response was rapid with normalization of the blood pressure after 4 hours. The vasopressors were discontinued on day 2. The leukocyte count was 6200 cells/mm3 at that time.

A blood culture that was drawn at admission grew N meningitidis, and a sputum culture grew N meningitidis and ß hemolytic Streptococcus, Lancefield group C. Intravenous penicillin G (400000 U/kg per day) was started on day 4; the other antimicrobials were discontinued. Prophylaxis with ciprofloxacin was given to family members and close contacts.

On day 4 of hospitalization, she complained of sudden-onset, severe, left-sided chest pain and difficulty in breathing. She was afebrile. A chest radiograph showed a large, left-sided pleural effusion. The results of an electrocardiogram were normal. Echocardiography revealed a small pericardial effusion and an incidental finding of partial anomalous pulmonary venous return. A spiral computed tomography (CT) of the chest showed no evidence of pulmonary embolus but did reveal extensive consolidation in the lower lobes of both lungs with a large, left-sided pleural effusion (Figure 1A).


Figure 1
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  		FIGURE 1 Axial CT images of the chest obtained on days 4 (A) and 17 (B) of hospitalization after the intravenous administration of contrast material. A large left-sided pleural effusion (A, arrow) and bilateral consolidations in the lung bases were present on the initial study. A large right-sided pleural effusion with underlying consolidation can be seen in B (arrow) with nearly complete resolution of the left-sided pleural effusion.

 
Video-assisted thoracoscopic surgery with insertion of 2 chest drains into the left pleural space was performed on day 5 and yielded yellow fluid compatible with an exudate (protein: 3.4 g/dL; glucose: 81 mg/dL; lactate dehydrogenase: 1190 U/L). The leukocyte count of the fluid was 2600 cells/mm3 with 61% neutrophils. The Gram stain revealed no bacteria, although extra- and intracellular diplococci were seen on a Wright stain of the fluid; the culture was negative. The chest pain decreased with evacuation of the pleural fluid, but the patient had continued fever, tachypnea, and oxygen requirement.

On hospital day 16, the patient complained of right-sided chest pain. The C-reactive protein was 218 mg/L; cultures of blood and urine were negative. A chest CT on hospital day 17 showed a large right-sided pleural effusion (Figure 1B). Video-assisted thoracoscopic surgery was done; many pleural loculated collections and adhesions were noted. Two chest drains were inserted into the right pleural space. Blood-tinged fluid compatible with an exudate (protein: 5.4 g/dL; glucose: <20 mg/dL; lactate dehydrogenase: 1491 U/L) was drained. The Gram stain revealed no bacteria, and the culture was negative.

After the procedure, the patient felt better and the chest pain improved. On hospital day 23, she became afebrile. The C-reactive protein was 122 mg/L. She was discharged on hospital day 24 and instructed to complete a 4-week course of penicillin therapy. The serum hemolytic complement profile was normal, and an enzyme-linked immunosorbent assay for HIV was negative.

Laboratory results that were available after discharge showed that the meningococcal blood and sputum isolates belonged to serogroup Y and lacked ß-lactamase activity (reported by the Illinois Department of Public Health). The capsular antigen of N meningitidis serogroup Y was detected by latex agglutination (Focus Technology, Cypress, CA) in the right-sided pleural fluid.

Susceptibility testing on the blood meningococcal isolate, performed at the Mayo Clinic, demonstrated the meningococcal isolate to be resistant to penicillin with a minimal inhibitory concentration (MIC) of 0.5 µg/mL by agar dilution and susceptible to ceftriaxone with an MIC ≤0.12 µg/mL. The MIC of penicillin, performed at the University of Chicago Hospitals Clinical Microbiology Laboratories, was 0.38 µg/mL by the Etest method. Subsequent testing that was performed at the Centers for Disease Control and Prevention (CDC) demonstrated an MIC of 0.25 µg/mL by using a broth microdilution technique.

DISCUSSION

Meningococcal pneumonia is infrequent, although it has been recognized for 100 years9 and was known to complicate influenza during the pandemic of 1918.10,11 Meningococcal pneumonia is estimated to occur in ~5% to 15% of patients with invasive meningococcal disease,2 although the precise incidence is difficult to establish because of uncertainty in establishing the cause of pneumonia. Isolation of the organism from sputum does not distinguish a carrier from an individual with meningococcal pneumonia. Other barriers to diagnosis are the specific media that are needed for cultivating the bacteria, the failure to consider the meningococcus as a cause of pneumonia, the nondistinctive clinical features of meningococcal pneumonia, and the estimated low rate of concomitant bacteremia (15–26% of meningococcal pneumonia cases).12–16

Among cases of N meningitidis pneumonia, empyema has been reported rarely. Herrick11 reported 1 case of pneumonia with empyema among 315 cases of meningococcal infection that were treated in a military hospital during World War I. It is interesting that the patient was co-infected with measles. In 1948, Brick17 reported the case of a 53-year-old man who had late latent syphilis and died from meningococcal empyema and congestive heart failure, although he was co-infected with Streptococcus pneumoniae. Darnell et al16 described in 1981 a 56-year-old woman who had pneumonia and empyema and was discharged on the 14th hospital day after pleural fluid drainage. Two blood cultures and the pleural fluid grew N meningitidis serogroup W-135. Sacks18 described in 1986 an elderly woman with blood and pleural fluid cultures that yielded N meningitidis serogroup C. No cases of empyema were found among 68 Air Force recruits with meningococcal pneumonia,15 and empyema was not reported in several large reviews of meningococcal disease.14,19,20 The most recent report of meningococcal empyema was published in 1986 by Burns,21 who described the only pediatric case, a 4-year-old boy who presented after a 3-week history of upper respiratory tract infection with a right middle and lower lobe pneumonia and a small pleural effusion. The blood was sterile, but the pleural fluid grew N meningitidis serogroup B. He was discharged on the fifth hospital day.

The prevalence of serogroup Y meningococcal disease has increased recently in the United States. In 1996–1998, one third of meningococcal infections were attributed to serogroup Y as opposed to ~2% of cases in 1988–1991.2 Serogroup Y is more likely than other serogroups to be associated with pneumonia.19,22,23 Among 88 cases of group Y meningococcal disease in American Air Force recruits in 1971–1974, 68 had infection limited to the lung. The diagnosis was based on a compatible clinical syndrome; chest radiograph findings; and a transtracheal, transthoracic, or blood culture that yielded the bacterium. Ten of the patients had accompanying meningococcemia, and 6 had meningitis.15 Pneumonia, therefore, predominated over meningococcemia and meningitis in a 4:1 ratio. Among the patients with pneumonia, the response to antibiotic therapy was prompt; 93% of the patients were afebrile within 3 days of antibiotic therapy. Only 1 patient, who had preexisting leukopenia, died. Among 58 cases of meningococcal pneumonia in 1974–1998, serogroup Y accounted for 44% of the cases. None had meningococcemia. Five (8.6%) of the patients died.3

Some features of our patient were unique: she was younger than most reported patients with meningococcal pneumonia and presented with meningococcemia and shock. The pulmonary disease was more severe than most reported patients with disease that is caused by serogroup Y, bilateral large empyemas were present, and, furthermore, they became evident late in the clinical course.

The pathogenesis of the right-sided pleural effusion that was diagnosed on hospital day 17 is uncertain. Late complications of meningococcal disease have been described secondary to an immune complex–mediated process and include arthritis, vasculitis, pericarditis, nephritis, and episcleritis.24–28 These complications tend to occur in the subacute phase, usually within 4 to 10 days (range: 2 to 16) after the onset of disease. Their onset is associated with a secondary rise in temperature, leukocytosis, and increase in the serum C-reactive protein concentration.29 The pathogenesis probably represents a type 3 immune complex hypersensitivity reaction. Pleuritis per se is rarely described in this context, although Goedvolk et al29 described pleuritis in the subacute phase of 5 (3.8%) of 130 children who were hospitalized for severe meningococcal disease in a PICU in the Netherlands. None of these children had pneumonia. In other reports that described pleuritis, it was associated with pericarditis.30–32 Therefore, it is possible that our patient had the late-onset pleural effusion as a manifestation of meningococcal immune complex disease. Some of the features are compatible: the delayed presentation, the secondary rise of temperature, and the increased level of C-reactive protein. However, such massive exudate with extensive loculations and adhesions was not described before. Therefore, the possibility of empyema on the right side is also a reasonable option.

For many years, it was believed that N meningitidis was uniformly susceptible to penicillin. However, since 1985, decreased susceptibility to penicillin has been noted in Spain and the United Kingdom.33,34 In certain areas of Spain, the prevalence of decreased susceptibility to penicillin increased from 0.4% of the isolates in 1985 to >55% in 1997.4 Subsequently, decreased penicillin susceptibility has been reported from other European countries, Israel, South America, Canada, Australia, and South Africa.4,35–37 Most MICs of penicillin have ranged from 0.06 to 0.8 µg/mL, but MICs >1 µg/mL also were noted occasionally.33,35

The mechanism of decreased penicillin susceptibility is believed to reflect mosaicism in the penicillin-binding protein 2 gene (penA) by transformation of DNA segments from naturally penicillin-resistant commensal Neisseria species into the penA gene of N meningitidis.7,34 The altered penA gene encodes a protein that has decreased affinity for penicillin. It is believed that production of the low-affinity penicillin-binding protein 2 confers low-level penicillin resistance (MIC: ~0.1 µg/mL). Higher level resistance is achieved by additional transformation of DNA, further altering the penA gene. Other changes, such as a postulated decreased permeability of the outer membrane, also may play a role. Similar transformation events have not been documented to affect penicillin-binding protein 1.34 The production of a ß-lactamase has been reported in rare instances.7,34,35,38

The CLSI, formerly known as the National Committee for Clinical Laboratory Standards, recommends a method for antimicrobial MIC testing for meningococci, but, until recently, breakpoints to define susceptibility were not established.39,40 In 2005, the CLSI promulgated definitions of penicillin susceptible (≤0.06 µg/mL), intermediate (0.12–0.25 µg/mL), and resistant (≥0.5 µg/mL) meningococcal isolates.8 The CLSI recommends the use of either the broth microdilution technique in cation-adjusted Mueller-Hinton broth supplemented with lysed horse blood or the agar dilution method with Mueller-Hinton agar supplemented with defibrinated sheep blood. Susceptibility testing by Etest was not addressed in the CLSI guidelines, but an interlaboratory comparison found 100% agreement between agar dilution and Etest methods for determining the MICs of penicillin for N meningitidis strains.39 A similar correlation was reported from the SENTRY surveillance program in North America.6 This is important because many laboratories use the Etest as the routine method to determine the MIC for meningococcal strains.39

Despite the emergence of penicillin resistance, none of the >900 US meningococcal isolates that were tested at the CDC in 1980–1990 had an MIC of penicillin >0.06 µg/mL.41 The first isolate with decreased susceptibility to penicillin in the United States was reported from North Carolina in October 1992.42 The patient was a 13-month-old girl with serogroup B meningococcemia and meningitis. The MIC of penicillin was 0.25 µg/mL. She was treated with ceftriaxone and recovered. In Kentucky in 1993, an 11-year-old had serogroup C meningococcal sepsis.43 The MIC of penicillin was 0.25 µg/mL, but an MIC of 0.5 µg/mL was found on retesting. The patient was treated successfully with cefotaxime.

In 1991–1992, CDC investigators found that 3 of 100 submitted isolates had decreased susceptibility to penicillin with an MIC of 0.125 µg/mL.41 All 3 isolates were from normally sterile sites, belonged to serogroup B, and were ß-lactamase negative. None of the 3 patients was treated solely with penicillin, and all recovered. Similar findings of low prevalence of decreased susceptibility in the United States (3% of isolates with MIC value of 0.12 µg/mL) were reported by Rosenstein et al5 after active surveillance.

The SENTRY program surveyed N meningitidis isolates in North America in 1998–19996 using the Etest method and found a higher prevalence of decreased susceptibility than previously reported. Sixteen (30.2%) of 53 isolates had decreased susceptibility with MICs ranging from 0.094 to 0.25 µg/mL. No isolate produced ß-lactamase. Serogroup Y comprised 24% of the resistant strains.

The clinical significance of decreased susceptibility to penicillin has been uncertain.2,7 There have been few reports of penicillin failure. An 18-year-old man who had meningococcal meningitis and was treated with low-dose penicillin (2 x 106 U/day) relapsed clinically on day 5 of treatment.44 The MIC of penicillin was 0.64 µg/mL. A 7-year-old girl with meningococcemia developed meningococcal meningitis while being treated with 300000 U/kg per day of penicillin.45 The MIC of penicillin was 0.25 µg/mL. In a case of a 16-year-old man who had meningococcal meningitis and was treated with 300000 U/kg per day of penicillin G, N meningitidis still could be isolated from the cerebrospinal fluid after 72 hours of antibiotic treatment. The MIC of penicillin was 0.5 µg/mL.46 A higher rate of complications, such as deafness, skin necrosis, and peripheral vein thrombosis, was found in pediatric patients who were infected with N meningitidis with MICs of penicillin of 0.25 to 0.5 µg/mL compared with patients who were infected with more susceptible isolates with an MIC <0.08 µg/mL.47 These reports suggest that the MIC interpretive standards defined by the CLSI have clinically important correlations. Reports of penicillin failure have not originated from the United States perhaps because penicillin rarely is the initial antimicrobial agent used to treat meningitis or sepsis.2

Our patient's isolate was tested for penicillin susceptibility in 2 laboratories and later at the CDC. The MIC of penicillin was in the resistant range at 1 laboratory (0.5 µg/mL), in an indeterminate zone beyond the intermediate-resistant range (0.38 µg/mL) in another laboratory, and at the upper limit of the intermediate-resistant range (0.25 µg/mL) at the CDC. All 3 MIC values were within a single doubling dilution. Our patient received 4 days of ceftriaxone therapy before high-dose penicillin was administered. The prolonged clinical course and development of empyema are compatible with a suboptimal clinical response to penicillin.

Our experience with this patient suggests that susceptibility testing should be performed in every case of N meningitidis isolation and treatment with a third-generation cephalosporin should be provided until the susceptibility results are known. Clinical suspicion of N meningitidis as a possible cause of respiratory symptoms accompanied by hypotension, even in the absence of a rash, may aid in the diagnosis and therefore in the treatment and provision of prophylaxis to contacts of patients with meningococcal disease.

ACKNOWLEDGMENTS

Dr Daum is the recipient of National Institute of Allergy and Infectious Disease grant RO1 AI40481-O1A1, Centers for Disease Control and Prevention grant RO1 CCR523379, and support from the Grant Health Care Foundation.

We are indebted to Drs Marc Fischer, Jean Patel, and David Lonsway at the Centers for Disease Control and Prevention for helpful discussions and for performing the MIC of penicillin. We also thank Drs John Marcinak and Mario Zaritzky at the University of Chicago for critical review of the manuscript and assistance with the radiologic images.

FOOTNOTES

Accepted Nov 4, 2005.

Address correspondence to Daniel Glikman, MD, Section of Pediatric Infectious Diseases, Wyler Pavilion, 5841 S Maryland Ave, MC 6054, Chicago, IL 60637. E-mail: dglikman{at}peds.bsd.uchicago.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.

REFERENCES

  1. Vieusseux M. Memories of the disease breaking out in Geneva during the spring of 1805 [in French]. J Med Chir Pharmacol. 1805;11 :163
  2. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hughes JM. Meningococcal disease. N Engl J Med. 2001;344 :1378 –1388[Free Full Text]
  3. Winstead JM, McKinsey DS, Tasker S, De Groote M, Baddour LM. Meningococcal pneumonia: characterization and review of cases seen over the past 25 years. Clin Infect Dis. 2000;30 :87 –94[CrossRef][ISI][Medline]
  4. Arreaza L, De la Fuente L, Vázquez JA. Antibiotic susceptibility patterns of Neisseria meningitidis isolates from patients and asymptomatic carriers. Antimicrob Agents Chemother. 2000;44 :1705 –1707[Abstract/Free Full Text]
  5. Rosenstein NE, Stocker SA, Popovic T, Tenover FC, Perkins BA. Antimicrobial resistance of Neisseria meningitidis in the United States, 1997. Clin Infect Dis. 2000;30 :212 –213[CrossRef][ISI][Medline]
  6. Richter SS, Gordon KA, Rhomberg PR, Pfaller MA, Jones RN. Neisseria meningitidis with decreased susceptibility to penicillin: report from the SENTRY antimicrobial surveillance program, North America, 1998–99. Diagn Microbiol Infect Dis. 2001;41 :83 –88[CrossRef][ISI][Medline]
  7. Oppenheim BA. Antibiotic resistance in Neisseria meningitidis. Clin Infect Dis. 1997;24 (suppl 1):S98–S101
  8. Clinical and Laboratory Standards Institute/NCCLS. Performance Standards for Antimicrobial Susceptibility Testing; Fifteenth Informational Supplement. Wayne, PA: Clinical and Laboratory Standards Institute; 2005. CLSI/NCCLS document M100-S15
  9. Jacobitz H. The Diplococcus meningtidis cerebrospinalis as the cause of lung and bronchi diseases [in German]. Z Hyg Infektionskr. 1907;56 :175 –192[CrossRef]
  10. Fletcher W. Meningococcus broncho-pneumonia in influenza. Lancet. 1919;1 :104 –105
  11. Herrick WW. Extra-meningeal meningococcus infections. Arch Intern Med. 1919;23 :409 –419[CrossRef][ISI]
  12. Putsch RW, Hamilton JD, Wolinsky E. Neisseria meningitidis, a respiratory pathogen? J Infect Dis. 1970;121 :48 –54[ISI][Medline]
  13. Witt D, Olans RN. Bacteremic W-135 meningococcal pneumonia. Am Rev Respir Dis. 1982;125 :255 –257[ISI][Medline]
  14. Stephens DS, Hajjeh RA, Baughman WS, Harvey RC, Wenger JD, Monica M. Sporadic meningococcal disease in adults: results of a 5-year population-based study. Ann Intern Med. 1995;123 :937 –940[Abstract/Free Full Text]
  15. Koppes GM, Ellenbogen C, Gebhart RJ. Group Y meningococcal disease in United States Air Force recruits. Am J Med. 1977;62 :661 –666[CrossRef][ISI][Medline]
  16. Darnell JC, Brandt MJ. Primary meningococcal pneumonia: a report of three cases. J Indiana State Med Assoc. 1981;74 :794 –798[Medline]
  17. Brick IB. Meningococcal pneumonia. Report of two cases with meningococcal effusion in one. N Engl J Med. 1948;238 :289 –291
  18. Sacks HS. Meningococcal pneumonia and empyema. Am J Med. 1986;80 :290 –291[CrossRef][ISI][Medline]
  19. Rosenstein NE, Perkins BA, Stephens DS, et al. The changing epidemiology of meningococcal disease in the United States, 1992–1996. J Infect Dis. 1999;180 :1894 –1901[CrossRef][ISI][Medline]
  20. Racoosin JA, Whitney CG, Conover CS, Diaz PS. Serogroup Y meningococcal disease in Chicago, 1991–1997. JAMA. 1998;280 :2094 –2098[Abstract/Free Full Text]
  21. Burns JL. Primary meningococcal pneumonia diagnosed by pleural fluid culture. Am J Dis Child. 1986;140 :188[Medline]
  22. Serogroup Y Meningococcal disease—Illinois, Connecticut, and selected areas, United States, 1989–1996. MMWR Morb Mortal Wkly Rep. 1996;45 :1010 –1014[Medline]
  23. Pastor P, Medley FB, Murphy TV. Meningococcal disease in Dallas County, Texas: results of a six-year population-based study. Pediatr Infect Dis J. 2000;19 :324 –328[CrossRef][ISI][Medline]
  24. Saslaw S, Diserens RV. Purulent pericardial effusion complicating meningococcal meningitis. N Engl J Med. 1960;263 :1074 –1075[ISI][Medline]
  25. Penny JL, Grace WJ, Kennedy RJ. Meningococcal pericarditis. A case report and review of the Literature. Am J Cardiol. 1966;18 :281 –285[CrossRef][ISI][Medline]
  26. Williams DN, Geddes AM. Meningococcal meningitis complicated by pericarditis, panophthalmitis, and arthritis. Br Med J. 1970;2 :93[ISI][Medline]
  27. Jarrett MP, Moses S, Barland P, Miller MH. Articular complications of meningococcal meningitis. Arch Intern Med. 1980;140 :1665 –1666[Abstract]
  28. Edwards MS, Baker CJ. Complications and sequelae of meningococcal infections in children. J Pediatr. 1981;99 :540 –545[CrossRef][ISI][Medline]
  29. Goedvolk CA, Rosenstiel IA, Bos AP. Immune complex associated complications in the subacute phase of meningococcal disease: incidence and literature review. Arch Dis Child. 2003;88 :927 –930[Abstract/Free Full Text]
  30. Moss W, Prince A. Pericarditis complicating meningococcal meningitis in a 7-month-old boy. Clin Pediatr (Phila). 1994;33 :169 –171[Free Full Text]
  31. Morse JR, Oretsky MI, Hudson JA. Pericarditis as a complication of meningococcal meningitis. Ann Intern Med. 1971;74 :212 –217[ISI][Medline]
  32. Miller GC, Calhoun Witham A. Delayed febrile pleuropericarditis after sepsis. A possible analogue of the postcardiotomy syndrome. Ann Intern Med. 1973;79 :194 –197[ISI][Medline]
  33. Sutcliffe EM, Jones DM, el-Sheikh S, Percival A. Penicillin-insensitive meningococci in the UK. Lancet. 1988;1 (8586):657 –658[ISI][Medline]
  34. Sáez-Nieto JA, Lujan R, Berrón S, et al. Epidemiology and molecular basis of penicillin-resistant Neisseria meningitidis in Spain: a 5-Year history (1985–1989). Clin Infect Dis. 1992;14 :394 –402[ISI][Medline]
  35. Botha P. Penicillin-resistant Neisseria meningitidis in Southern-Africa. Lancet. 1988;1 (8575–6):54
  36. Block C, Davidson Y, Melamed E, Keller N. Susceptibility of Neisseria meningitidis in Israel to penicillin and other drugs of interest. J Antimicrob Chemother. 1993;32 :166 –168[Free Full Text]
  37. Riley G, Brown S, Krishnan C. Penicillin resistance in Neisseria meningitidis. N Engl J Med. 1991;324 :997[ISI][Medline]
  38. Ikeda F, Tsuji A, Kaneko Y, Nishida M, Goto S. Conjugal transfer of beta-lactamase-producing plasmids of Neisseria gonorrhoeae to Neisseria meningitidis. Microbiol Immunol. 1986;30 :737 –742
  39. Vazquez JA, Arreaza L, Block C, et al. Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections. Antimicrob Agents Chemother. 2003;47 :3430 –3434[Abstract/Free Full Text]
  40. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing; Eleventh Informational Supplement. Wayne, PA: National Committee for Clinical Laboratory Standards; 2003. NCCLS document M100-S13
  41. Jackson LA, Tenover FC, Baker CJ, et al. Prevalence of Neisseria meningitidis relatively resistant to penicillin in the United States, 1991. J Infect Dis. 1994;169 :438 –441[ISI][Medline]
  42. Woods CR, Smith AL, Wasilauskas BL, Campos J, Givner LB. Invasive disease caused by Neisseria meningitidis relatively resistant to penicillin in North Carolina. J Infect Dis. 1994;170 :453 –456[ISI][Medline]
  43. Buck GE, Adams M. Meningococcus with reduced susceptibility to penicillin isolated in the United States. Pediatr Infect Dis J. 1994;13 :156 –157[ISI][Medline]
  44. Turner PC, Southern KW, Spencer NJB, Pullen H. Treatment failure in meningococcal meningitis. Lancet. 1990;335 :732 –733[ISI][Medline]
  45. Casado-Flores J, Osona B, Domingo P, Barquet N. Meningococcal meningitis during penicillin therapy for meningococcemia. Clin Infect Dis. 1997;25 :1479[ISI][Medline]
  46. Bardi L, Badolati A, Corso A, Rossi MA. Failure of the treatment with penicillin in a case of Neisseria meningitidis meningitis. Medicina (B Aires). 1994;54 :427 –430[Medline]
  47. Pérez-Trallero E, Aldamiz-Echeverria L, Pérez-Yarza EG. Meningococci with increased resistance to penicillin. Lancet. 1990;335 :1096[CrossRef][ISI][Medline]
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