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Overwhelming Postsplenectomy Infection in a Patient With Penicillin-Resistant Streptococcus pneumoniae
Kelly K. Machesky, MD;
Ralph D. Cushing, MD
Arch Fam Med. 1998;7:178-180.
ABSTRACT
Overwhelming postsplenectomy infection is a fulminant process that carries a poor prognosis. Streptococcus pneumoniae is the most likely organism to cause disease. Infection with penicillin-resistant S pneumoniae is increasing; its prevalence ranges from 6.6% to 50% in the United States. If meningeal involvement with resistant pneumococcus is suspected, it should be treated with a third-generation cephalosporin and vancomycin hydrochloride. The long-term management of asplenic patients should focus on preventing infection. The current guidelines and recommendations for vaccination are reviewed. Educating these patients to contact their physician at the first sign of minor illness is also beneficial. The use of antibiotic prophylaxis remains a controversy and is best left to the discretion of the physician.
INTRODUCTION
Asplenic patients are at risk for many infections. When fulminant bacterial sepsis occurs, the term commonly found in the literature is overwhelming postsplenectomy infection (OPSI).1 We discuss a patient who presented with OPSI and who had bacteremia with Streptococcus pneumoniae serotype 23F, which is resistant to penicillin. We also review the literature regarding OPSI, appropriate therapeutic management for pneumococcal resistance, and vaccination.
REPORT OF A CASE
A 43-year-old white man presented with fever, headache, and generalized myalgia for 1 week. Breathlessness, abdominal pain, and rigors began on the day of admission. He denied nausea, vomiting, diarrhea, photophobia, and stiff neck. Four weeks prior to admission, he had an upper respiratory tract infection and completed a 10-day course of amoxicillin. He had had a splenectomy for trauma in 1973 with one previous episode of OPSI approximately 18 months after his surgery. We determined from an extensive interview with him that he had not received the pneumococcal vaccine either in the postoperative course or during the 23-year period following his surgery. He had not received penicillin prophylaxis.
Vital signs on admission were blood pressure 101/57 mm Hg, pulse rate 125/min, respirations 28/min, and oral temperature of 38.03°C. An arterial blood gas measurement with the patient breathing room air was pH 7 of .44, PCO2 of 32.0 mm Hg, PO2 of 68.6 mm Hg, HCO3 of 21.0 mmol/L, and oxygen saturation of 93.0%. An initial complete blood cell count revealed a white blood cell count of 25.1x109L with 80% neutrophils and 12% bands. Results from the remaining studies, including x-ray films, were all normal. The patient began receiving ceftriaxone sodium, 1 g/12 h, for presumed pneumonia. Both of 2 blood cultures showed S pneumoniae with a penicillin minimum inhibitory concentration (MIC) of more than 3 µg/mL, confirmed by the Michigan Department of Public Health.
Streptococcus pneumoniae grew from blood cultured 27 hours after initial therapy in 1 of 2 bottles. The patient developed headache and photophobia despite full-dose ceftriaxone therapy. Analysis of a lumbar puncture revealed 214 neutrophils, 51 red blood cells, a glucose level of 2.8 mmol/L (50 mg/dL) (normal range, 2.8-4.4 mmol/L [50-80 mg/dL]), and a protein level of 244 mg/dL (normal range, 15-45 mg/dL). Gram stain, cultures, and bacterial antigens were all negative for organisms. A repeated chest x-ray film showed bilateral infiltrates. Vancomycin therapy was added because of the reported MICs. Although the cerebrospinal fluid Gram stain showed no organisms, we diagnosed meningitis based on clinical findings, cerebrospinal fluid cell count, and protein levels. The patient had a complete recovery and was discharged from the hospital after 2 weeks of intravenous antibiotic therapy. He received the pneumococcal vaccine on the day of discharge and was instructed to follow up at our Family Practice Clinic.
REVIEW
CLINICAL REVIEW
This patient was typical of most patients with anatomic asplenia. His first episode of OPSI occurred within 18 months of his surgery. Adults who undergo splenectomy for trauma have an incidence of OPSI of 0.27% to 0.66% with the highest incidence in the early postoperative period and approximately 70% of incidents occurring in the first 7 years.1
Postsplenectomy sepsis may present with fever, chills, malaise, myalgia, diarrhea, or vomiting. Coexisting infections may include pneumonia and meningitis. A large percentage of cases may have no focus for infection but present with a high-grade bacteremia.1 The patient's clinical course can rapidly deteriorate despite appropriate therapy. Progression to hypotension, respiratory distress, disseminated intravascular coagulation, and multisystem organ failure can ultimately occur. Postmortem examination has frequently revealed bilateral adrenal hemorrhages.1
The spleen has 2 immune functions in the defense against pneumococcal infection: it is a site of production of specific antibodies and it functions as a filter system for opsonized bacteria. The spleen controls the circulating B cells capable of differentiating into antipneumococcal capsular polysaccharide antibody–secreting B cells. Thus, in patients who have undergone splenectomy there will be a long-standing B-cell defect with an impaired immune response to pneumococcal capsular polysaccharide.2 Normally the splenic microcirculation allows only 10% of arterial blood to bypass its network. Bacteria are forced to percolate through the fine meshwork and have intimate contact with the splenic macrophages, which have a superior ability to phagocytize opsonized encapsulated organisms.
PNEUMOCOCCUS
Encapsulated organisms are frequently involved in sepsis in patients who have undergone splenectomy. Approximately 50% of cases are caused by S pneumoniae, and 25% by Haemophilus influenzae, Neisseria meningitis, and Streptococcus pyogenes. Rarer pathogens making up the last 25% include Gram-negative organisms such as Pseudomonas species.3
In our patient, the infecting organism was S pneumonia e serotype 23F, which is highly resistant to penicillin. In the general population the emergence of the first penicillin-resistant S pneumoniae was reported in 1967.4 Now it is common worldwide, with the greatest prevalence reported in Hungary (59%) and South Africa (45%). In the United States, recent nationwide surveys indicate that 6.6% of strains received from sterile sites were resistant to penicillin, yet rates in excess of 20% have been reported by some institutions.4-5 In an alarming 1995 report from rural Kentucky, 50% of pneumococcal isolates were found to be penicillin-resistant.6 A study by Hoffman et al7 in Atlanta found variation in resistant species not only by geographic region but also by patient population. African Americans had a higher incidence of invasive pneumococcal infection but whites were more likely to be infected with resistant species. This relationship can possibly be attributed to the more liberal use of antibiotics among whites.
Pneumococci not only exhibit more non– -lactamase–mediated resistance to penicillin and other -lactam antibiotics than they previously did, but they also are showing more resistance to non–-lactam antimicrobials.6 Reports from the United States in 1987 showed resistance of pneumococcal isolates to tetracycline hydrochloride 2.5%, a combination of trimethoprim and sulfamethoxazole 2.1%, and erythromycin 1.1%. European rates of resistance have been much higher—for tetracycline, as high as 70.9%, for trimethoprim and sulfamethoxazole, 53.0%, and for erythromycin, up to 51.0%. Resistance among the -lactam antibiotics, eg, ceftriaxone, increases proportionately as the MIC increases.6
Therapy for suspected pneumococcal illness, regardless of patient population, should be based on whether the site of infection is meningeal or nonmeningeal. The drugs of choice for suspected bacterial meningitis are ceftriaxone or cefotaxime sodium, based on their bactericidal activity and excellent penetration into the cerebrospinal fluid. If the organism is sensitive or has intermediate resistance to penicillin (MIC >0.1-1.0 µg/mL), cephalosporin therapy alone is justified. If high-level resistance (MIC >2.0 µg/mL) is encountered, vancomycin and possibly rifampin are recommended.6 Nonmeningeal infections with intermediate resistance to penicillin may be treated with high-dose penicillin G, or, if that is ineffective, cefotaxime or ceftriaxone may be used.8 Again, if high-level penicillin resistance or resistance to cephalosporins is encountered, vancomycin may be needed.6, 8-9
VACCINATION
Prevention of infection is important for patients who are immunocompromised. The pneumococcal vaccine was first available in 1977. It was reformulated in 1983 to include 23 serotypes that are responsible for approximately 85% to 88% of pneumococcal infections. Currently it is estimated that only 10% of patients for whom it is recommended actually receive the vaccine.10-11
The most recent guidelines by the Advisory Committee on Immunization Practices11 state that those patients at increased risk for invasive pneumococcal infection should receive the vaccine. This includes patients with diabetes mellitus, alcoholism, cirrhosis, cerebrospinal fluid leaks, chronic cardiovascular disease, congestive heart failure, or chronic obstructive pulmonary disease; persons aged 2 years or older with symptomatic or asymptomatic human immunodeficiency virus; healthy persons who have reached age 65 years; and those aged 2 years or older with immunosuppression or chronic illness, or with functional or anatomic asplenia.10-11 For patients who undergo elective splenectomy, the vaccine should be given 2 weeks prior to surgery.11-12 In those patients who require splenectomy secondary to trauma, a study showed patients with multiple organ trauma can be successfully immunized immediately after splenectomy.13 Revaccination 5 years later is recommended for asplenic patients and patients at risk for declining antibody levels, eg, those with nephrotic syndrome or translant recipients. We strongly advocate that practitioners review these guidelines. Some authors also recommend that the asplenic patient receive the conjugated H influenzae and meningococcal vaccines.16-17
A surveillance study conducted in US hospitals by the Centers for Disease Control and Prevention from 1978 to 1992 found some limitations to the vaccine. It is difficult to prove its efficacy for nonbacteremic pneumococcal pneumonia because of the low specificity of sputum analysis. Six serotypes (6B, 10A, 18C, 19F, 22F, and 23F) included in the 23-valent vaccine are less immunogenic than the others.10 Serotype 23F, the infecting organism in our patient, has high-level penicillin resistance increasingly reported worldwide and is of low immunogenicity.7, 10, 14-15
EDUCATION
After OPSI is diagnosed, mortality rates as high as 50% to 70% are reported despite appropriate antibiotics and medical management.18 Educating patients regarding the signs and symptoms of infection is effective for preventing progression of the disease. A prospective analysis by Green et al19 of 144 patients with splenectomy secondary to trauma, blunt or penetrating, revealed a mortality of only 7% due to major infectious complications that included OPSI, pneumonia, meningitis, abscess, and others. Their decreased overall mortality was attributed to the close asplenic registry follow-up of patients who were educated to seek medical attention at the earliest sign of minor infection.
ANTIBIOTIC PROPHYLAXIS
There is controversy in the literature regarding antibiotic prophylaxis. Chattopadhyay12 recommends long-term (10 years or more) therapy. Of the patients followed in the asplenic registry of Green et al,19 none had received prophylactic antibiotic therapy and their OPSI mortality rate was lower than the national average. Other authors would advocate prophylaxis during the first 2 postoperative years for patients who have undergone splenectomy, for children younger than 5 years, and for all those patients who are severely immunocompromised.20 Most authors would recommend prophylaxis in pediatric patients until age 18 and for at least 5 years in adults. The antibiotic chosen was penicillin V, 250 mg twice a day; but because penicillin has variable gastrointestinal absorption and lacks the ability to protect from H influenzae, amoxicillin, 250 mg/d, is now recommended.17
| Editor's Note: I was the physician for several members of a family with hereditary spherocytosis. It was really tragic when an adult family member, who was not a patient of mine, died, unvaccinated, of pneumococcal sepsis. The family thanked me profusely for giving them the vaccine. Remember to vaccinate and give booster shots!—Marjorie A. Bowman, MD, MPA
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CONCLUSIONS
Asplenic patients are at risk for developing serious infections after even minor illness. In the management of these patients, early intervention with antibiotics and possible hospitalization may be necessary. The antibiotics of choice are currently ceftriaxone and vancomycin for patients with suspected pneumococcal meningeal infection.
Physicians should vaccinate their asplenic patients with the pneumococcal vaccine and possibly also the H influenzae and meningococcal vaccines. However, one of the most penicillin-resistant serotypes (23F) included in the vaccine is of low immunogenicity and the clinician must keep OPSI in mind even when treating patients who have been vaccinated. Educating patients about their disease has been reported to decrease overall mortality,19 but the use of antibiotic prophylaxis is still controversial.
AUTHOR INFORMATION
Accepted for publication January 16, 1997.
Corresponding author: Ralph D. Cushing, MD, Bon Secours Hospital, 468 Cadieux Rd, Grosse Pointe, MI 48230.
From Bon Secours Hospital, Grosse Pointe, Mich.
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