likely. Legionella spp. and cytomegalovirus pneumonia are generally not associated with nodules and have either lobar infiltrates or diffuse infiltrates.
IV-48. The answer is E. (Chap. 133) All bacteria, both gram negative and gram positive, have rigid cell walls that protect bacterial intracellular hyperosmolarity from the host environment. Peptidoglycan is the present in both gram-negative and gram-positive bacteria, but only gram-negative bacteria have an additional outer membrane external to peptidoglycan. Many antibiotics target cell wall synthesis and thus lead to inhibition of growth or cell death. These antibiotics include bacitracin, glycopeptides such as vancomycin, and β-lactam antibiotics. Macrolides such as azithromycin, lincosamides (clindamycin), linezolid, chloramphenicol, aminoglycosides such as tobramycin, mupirocin, and tetracycline all inhibit protein synthesis. Sulfonamides and trimethoprim interrupt cell metabolism. Rifampin and metronidazole alter nucleic acid synthesis. The quinolones, such as ciprofloxacin, and novobiocin inhibit DNA synthesis. Finally, polymixins, gramicid, and daptomycin disrupt the cellular membrane.
IV-49. The answer is B. (Chap. 133) The patient presents with evidence of methicillin-resistant Staphylococcus aureusľassociated soft tissue infection that has failed therapy with clindamycin. Linezolid is an appropriate choice for antibiotic coverage in this situation. Subsequent development of neurologic symptoms, including agitated delirium, evidence of autonomic instability coupled with tremor, muscular rigidity, hyperreflexia, and clonus, suggests serotonin syndrome. Because linezolid is a monoamine oxidase inhibitor, it interacts with selective serotonin reuptake inhibitors and can cause serotonin syndrome. Other potential triggers include tyramine-rich foods and sympathomimetics such as phenylpropanolamine. The other drugľdrug combinations in the answer choices are not described to be associated with serotonin syndrome.
IV-50. The answer is A. (Chap. 134) Pneumococcal infections, particularly pneumonia, remain a worldwide public health problem. Intermittent colonization of the nasopharynx by pneumococcus transmitted by respiratory droplet is common and is the likely reservoir for invasive disease. Infants and elderly adults are at greatest risk of developing invasive pneumococcal disease (IPD) and death. In the developed world, children are the most common source of pneumococcal transmission. By 1 year of age, 50% of children have had at least one episode of colonization. Prevalence studies show carriage rates of 20% to 50% in children up to 5 years old and up to 15% for adults. These numbers approach 90% for children and 40% for adults in the developing world. Pneumococcal vaccination has dramatically impacted the epidemiology with reduced IPD in the United States attributable to reductions in serotypes included in the vaccine. Similar reductions have been observed in other countries implementing routine childhood vaccinations; however, in certain populations (Alaska native populations and United Kingdom), the reduction in vaccine covered serotype cases has been offset by increases in nonvaccine serotypes. Case fatality rates caused by pneumococcal pneumonia vary by host factors, age, and access to care. Interestingly, there appears to be no reduction in case fatality during the first 24 hours of hospitalization since the introduction of antibiotics. This is likely because of the development of severe multiorgan failure as a result of severe infection. Appropriate care in an intensive setting can reduce case fatality rate for severe infection. Outbreaks of disease are well recognized in crowded settings with susceptible individuals, such as infant daycare facilities, military barracks, and nursing homes. Furthermore, there is a clear association between preceding viral respiratory disease (especially but not exclusively influenza) and risk of secondary pneumococcal infections. The significant role of pneumococcal pneumonia in the morbidity and mortality associated
with seasonal and pandemic influenza is increasingly recognized.
IV-51. The answer is C. (Chap. 134) This elderly man presents with a typical story of pneumococcal pneumonia. His age, chronic conditions, and nursing home residence put him a high risk of invasive disease acquisition. Outbreaks commonly occur in crowded environments or nursing homes often after preceding upper respiratory or influenza viral infections and are spread through respiratory droplets. Although the differential diagnosis includes viral pathogens, mycoplasmas, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, and Legionella spp., pneumococcal disease remains most common in this demographic. Blood cultures, even in severe disease are positive in fewer than 30% of cases. Diagnosis relies on a positive culture from blood or sputum or a positive urinary antigen test result. Urinary antigen testing has a high positive predictive value in adults because the intermittent colonization rate is low. The urinary antigen test is less specific for invasive disease in children who may be colonized. The radiograph in this case is typical for consolidation (with air bronchograms) of the right lower lobe. The clear right heart border and confinement below the major fissure suggests unilobar disease. With time and hydration, further radiologic extension may be apparent. Parapneumonic (noninfected) pleural effusions are common. The most common focal complication of pneumococcal disease is empyema, occurring in approximately 5% of cases. It should be suspected in cases of new or enlarging pleural effusion or persistent fever particularly after initiation of therapy. Meningitis may occur from hematogenous spread in conjunction with pneumonia or may be the sole presenting syndrome of pneumococcal infection. Pneumococcal resistance to penicillin has increased dramatically since the 1990s, and it is not recommended for empiric therapy of acute pneumonia. However, in culture-proven cases with minimal inhibitory concentration below 2 μg/mL, penicillin may remain an appropriate therapeutic choice for severe disease or meningitis.
IV-52 and IV-53. The answers are E and A, respectively. (Chaps. 134 and 143) In a previously healthy student, particularly one living in a dormitory, Streptococcus pneumoniae and Neisseria meningitides are the pathogens most likely to be causing community-acquired bacterial meningitis. As a result of the increasing prevalence of penicillin- and cephalosporin-resistant streptococci, initial empirical therapy should include a third- or fourth-generation cephalosporin plus vancomycin. Dexamethasone has been shown in children and adults to decrease meningeal inflammation and unfavorable outcomes in acute bacterial meningitis. In a recent study of adults, the effect on outcome was most notable in patients with S. pneumoniae infection. The first dose (10 mg IV) should be administered 15 to 20 minutes before or with the first dose of antibiotics and is unlikely to be of benefit unless it is begun 6 hours after the initiation of antibiotics. Dexamethasone may decrease the penetration of vancomycin into the cerebrospinal fluid.
IV-54. The answer is B. (Chap. 135) Although new genetic diagnostic kits for distinguishing microbes are becoming more common, basic biochemical characterization of bacterial pathogens is still widely used in microbiology laboratories. Clinicians should be familiar with the most common of these techniques when interpreting laboratory results. Whereas all staphylococci are catalase positive, streptococci are catalase negative. Whereas S. aureus are coagulase positive, Staphylococcus epidermidis (as well as S. hominis, S. saprophyticus, and others) are coagulase negative. This is the initial result that can make this important clinical distinction. Lactose fermentation is used to distinguish many gram-negative bacteria. Salmonella, Proteus, and Shigella spp. and Pseudomonas aeruginosa are unable to ferment lactose. The oxidase test is commonly used to identify P. aeruginosa. The urease
test is used to identify Proteus spp., Helicobacter spp., and other gram-negative organisms.
IV-55. The answer is D. (Chap. 135) The major clinical concern in this patient is epidural abscess or vertebral osteomyelitis, as well as line infection caused by Staphylococcus aureus. These concerns plus her significant likelihood of clinical deterioration necessitate close inpatient monitoring. Empiric therapy for methicillin-resistant S. aureus and gram-negative bacteria is warranted after obtaining blood cultures pending further evaluation. Metastatic seeding during S. aureus bacteremia has been estimated to occur as often as 30% of the time. The bones, joints, kidneys, and lungs are the most common sites. Metastatic infection to the spine should be evaluated in an emergent fashion with magnetic resonance imaging. The dialysis catheter should be removed because it is infected based on clinical examination. Infective endocarditis is a major concern. This diagnosis is based on positive blood culture results and either a vegetation on echocardiogram, new pathologic murmur, or evidence of septic embolization on physical examination. A transthoracic echocardiogram is warranted in the evaluation for endocarditis (a disease that this patient is at risk for). However, it need not be ordered emergently because it will not impact management during the initial phase of hospitalization. Moreover, because the diagnosis can only be established in the presence of positive blood cultures (or in rare cases serology of a difficult-to-culture organism), a rational approach is to await positive blood cultures before ordering an echocardiogram.
IV-56. The answer is C. (Chap. 135) In the past 10 years, numerous outbreaks of community-based infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in individuals with no prior medical exposure have been reported. These outbreaks have taken place in both rural and urban settings in widely separated regions throughout the world. The reports document a dramatic change in the epidemiology of MRSA infections. The outbreaks have occurred among such diverse groups as children, prisoners, athletes, Native Americans, and drug users. Risk factors common to these outbreaks include poor hygienic conditions, close contact, contaminated material, and damaged skin. The community-associated infections have been caused by a limited number of MRSA strains. In the United States, strain USA300 (defined by pulsed-field gel electrophoresis) has been the predominant clone. Although the majority of infections caused by this community-based clone of MRSA have involved the skin and soft tissue, 5% to 10% have been invasive, including severe necrotizing lung infections, necrotizing fasciitis, infectious pyomyositis, endocarditis, and osteomyelitis. The most feared complication is a necrotizing pneumonia that often follows influenza upper respiratory infection and can affect previously healthy people. This pathogen produces the Panton-Valentine leukocidin protein that forms holes in the membranes of neutrophils as they arrive at the site of infection and serves as marker for this pathogen. An easy way to identify this strain of MRSA is its sensitivity profile. Unlike MRSA isolates of the past, which were sensitive only to vancomycin, daptomycin, quinupristinľdalfopristin, and linezolid, CA-MRSA are almost uniformly susceptible to trimethoprimľsulfamethoxazole and doxycycline as well. The organism is also usually sensitive to clindamycin. The term community acquired has probably outlived its usefulness because this isolate has become the most common S. aureus isolate causing infection in many hospitals around the world.
IV-57. The answer is A. (Chap. 135) Vancomycin remains the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA). New patterns of staphylococcal resistance are developing including a strain (VISA, first reported in Japan) that shows vancomycin intermediate resistance. Of the drugs listed all have activity against MRSA. Telavancin is a derivative of vancomycin that is approved by the
U.S. Food and Drug Administration for complicated skin and soft tissue infections. VISA strains appear to be susceptible. Linezolid is bacteriostatic against staphylococci and has oral and parenteral formulations. Quinupristinľdalfopristin is bactericidal against all staphylococcal strains, including VISA. It has been used in severe MRSA infections. Daptomycin is not effective for respiratory infections. It can be used for bacteremia and right-sided endocarditis.
IV-58. The answer is E. (Chap. 135) Probably because of its ubiquity and ability to stick to foreign surfaces, Staphylococcus epidermidis is the most common cause of infections of central nervous system shunts as well as an important cause of infections on artificial heart valves and orthopedic prostheses. Corynebacterium spp. (diphtheroids), similar to S. epidermidis, colonize the skin. When these organisms are isolated from cultures of shunts, it is often difficult to be sure if they are the cause of disease or simply contaminants. Leukocytosis in cerebrospinal fluid, consistent isolation of the same organism, and the character of a patientĺs symptoms are all helpful in deciding whether treatment for infection is indicated.
IV-59. The answer is D. (Chap. 135) This patient has infectious pyomyositis, a disease of the tropics and of immunocompromised hosts such as patients with poorly controlled diabetes mellitus or AIDS. The pathogen is usually Staphylococcus aureus. Management includes aggressive debridement, antibiotics, and attempts to reverse the patientĺs immunocompromised status. Clostridium perfringens may cause gas gangrene, particularly in devitalized tissues. Streptococcal infections may cause cellulitis or an aggressive fasciitis, but the presence of abscesses in a patient with poorly controlled diabetes makes staphylococcal infection more likely. Polymicrobial infections are common in diabetic ulcers, but in this case, the imaging and physical examination show intramuscular abscesses.
IV-60. The answer is D. (Chap. 136) Recurrent episodes of rheumatic fever are most common in the first 5 years after the initial diagnosis. Penicillin prophylaxis is recommended for at least this period. After the first 5 years, secondary prophylaxis is determined on an individual basis. Ongoing prophylaxis is currently recommended for patients who have had recurrent disease, have rheumatic heart disease, or work in occupations that have a high risk for reexposure to group A streptococcal infection. Prophylactic regimens are penicillin V, PO 250 mg bid; benzathine penicillin, 1.2 million units IM every 4 weeks; and sulfadiazine, 1 g PO daily. Polyvalent pneumococcal vaccine has no cross-reactivity with group A streptococcus.
IV-61. The answer is E. (Chap. 136) Necrotizing fasciitis involves the superficial or deep fascia (or both) investing the muscles of an extremity or the trunk. The source of the infection is either the skin, with organisms introduced into tissue through trauma (sometimes trivial), or the bowel flora, with organisms released during abdominal surgery or from an occult enteric source, such as a diverticular or appendiceal abscess. The inoculation site may be unapparent and is often some distance from the site of clinical involvement; for example, the introduction of organisms via minor trauma to the hand may be associated with clinical infection of the tissues overlying the shoulder or chest. Cases originating from the skin are most commonly caused by infection with Streptococcus pyogenes (group A streptococcus), sometimes with Staphylococcus aureus coinfection. In this case, the presence of fasciitis without myositis (which is more commonly caused by staphylococci) makes S. pyogenes the most likely organism. The onset of disease is often acute and the course fulminant. Although pain and tenderness may be severe, physical findings may be subtle initially. Local anesthesia (caused by cutaneous nerve infarction) and skin mottling are late findings. Cases associated with the bowel flora are usually
polymicrobial, involving a mixture of anaerobic bacteria (e.g., Bacteroides fragilis or anaerobic streptococci) and facultative organisms (usually gram-negative bacilli). Necrotizing fasciitis is a surgical emergency with extensive debridement potentially life saving. At surgery, the extent of disease is typically more extensive than clinically or radiologically indicated. Antibiotic therapy is adjunctive. Patients with necrotizing fasciitis may develop streptococcal toxic shock syndrome. Streptococcus pneumoniae and Staphylococcus epidermidis are not causes of necrotizing fasciitis. Clostridium difficile causes antibiotic-associated colitis.
IV-62. The answer is D. (Chap. 136) Streptococcus agalactiae is the only species of group B streptococci (GBS) and is a major cause of sepsis and meningitis in neonates. The infection in neonates is acquired by passage through a maternally colonized birth canal. Although 40% to 50% of neonates born of colonized mothers will themselves become colonized, only 1% to 2% develop infection. GBS is also a cause of peripartum fever and can cause significant endometritis or chorioamnionitis. Vaginal swab culture results are typically positive. Risk factors for infection of the mother and child include premature labor and prolonged rupture of membranes. Treatment is with penicillin. The Centers for Disease Control and Prevention recommends screening pregnant women for anogenital colonization at 35 to 37 weeks of pregnancy by a swab culture of the lower vagina and anorectum. Intrapartum chemoprophylaxis is recommended for culture-positive women.
IV-63. The answer is B. (Chap. 137) Enterococci are the second most common organisms (after staphylococci) isolated from hospital-associated infections in the United States. Although Enterococcus faecalis remains the predominant species recovered from nosocomial infections, the isolation of E. faecium has increased substantially in the past 10 to 15 years. More than 80% of E. faecium isolates recovered in U.S. hospitals are resistant to vancomycin and more than 90% are resistant to ampicillin. The most important factors associated with vancomycin-resistant enterococci (VRE) colonization and persistence in the gut include prolonged hospitalization; long courses of antibiotic therapy; hospitalization in long-term-care facilities, surgical units, or intensive care units; organ transplantation; renal failure (particularly in patients undergoing hemodialysis) or diabetes; high APACHE scores; and physical proximity to patients infected or colonized with VRE or to these patientsĺ rooms. VRE infection increases the risk of death, independent of the patientĺs clinical status, over that among individuals infected with a glycopeptide-susceptible enterococcal strain.
IV-64. The answer is B. (Chap. 137) This patient has enterococcal endocarditis, which often occurs in patients with underlying gastrointestinal or genitourinary pathology. Enterococcus faecalis is a more common causative organism than E. faecium in community-acquired endocarditis. Patients tend to more commonly be men with underlying chronic disease. The typical presentation is one of subacute bacterial endocarditis and with involvement of the mitral or aortic valves. Prolonged therapy beyond 4 to 6 weeks is often necessary for organisms with drug resistance. Complications requiring valve replacement are common. Enterococci are intrinsically resistant or tolerant to several antimicrobial agents (with tolerance defined as lack of killing by drug concentrations 16 times higher than the minimal inhibitory concentration). Monotherapy for endocarditis with a β-lactam antibiotic (to which many enterococci are tolerant) has produced disappointing results with low cure rates at the end of therapy. However, the addition of an aminoglycoside to a cell wallľactive agent (a β-lactam or a glycopeptide) increases cure rates and eradicates the organisms; moreover, this combination is synergistic and bactericidal in vitro. Therefore, combination therapy with a cell wallľactive agent and
an aminoglycoside is the standard of care for endovascular infections caused by enterococci. This synergistic effect can be explained, at least in part, by the increased penetration of the aminoglycoside into the bacterial cell, presumably as a result of cell wall alterations attributable to the β-lactam or glycopeptide.
IV-65. The answer is D. (Chap. 137) Resistance to ampicillin and vancomycin is far more common in strains of Enterococcus faecium than E. faecalis. Linezolid and quinupristinľdalfopristin are approved by the U.S. Food and Drug Administration for the treatment of some vancomycin-resistant enterococci (VRE) infections. Linezolid is not bactericidal, and its use in severe endovascular infections has produced mixed results; therefore, it is recommended only as an alternative to other agents. Quinupristinľdalfopristin is not active against most E. faecalis isolates. Resistance to VRE strains of E. faecium is also emerging with increasing usage. Cephalosporins are generally inactive against enterococcal infections.
IV-66. The answer is B. (Chap. 138) Rhodococcus spp., including R. equi, are phylogenetically related to the corynebacteria. They predominantly cause necrotizing lung infections in immunocompromised hosts. The differential diagnosis of the cavitating lung lesions includes tuberculosis, Nocardia infection, and septic emboli. The organisms can initially be mistaken for corynebacteria, but they should not be misconstrued as skin contaminants. The organism is routinely susceptible to vancomycin, which is considered the drug of choice. Infection caused by R. equi has also been treated successfully with antibiotics that penetrate intracellularly, including macrolides, clindamycin, trimethoprimľ sulfamethoxazole, rifampin, tigecycline, and linezolid. β-Lactam antibiotics are not effective.
IV-67. The answer is D. (Chap. 139) Listeria meningitis typically affects elderly and the chronically ill individuals. It is frequently a more subacute (developing over days) illness than other etiologies of bacterial meningitis. It may be mistaken for aseptic meningitis. Meningeal signs, including nuchal rigidity, are less common, as is photophobia, than in other more acute causes of bacterial meningitis. Typically, white blood cell (WBC) counts in the cerebrospinal fluid range from 100 to 5000/μL with a less pronounced neutrophilia. About 75% of patients will have a WBC count below 1000/μL. Gram stain is only positive in 30% to 40% of cases. Case fatality rates are approximately 20%.
IV-68. The answer is A. (Chap. 139) Listeria monocytogenes causes gastrointestinal (GI) illness via ingestion of food that has been contaminated with high concentrations of bacteria. The bacteria may survive and multiply at refrigeration temperatures; therefore, deli meats, soft cheeses, hot dogs, and milk are common sources. The attack rate is very high, with close to 100% of exposed patients experiencing symptoms. Symptoms develop within 48 hours of exposure, and there is no prolonged asymptomatic carrier state. Person-to-person spread (other than vertically from mother to fetus) does not appear to occur during outbreaks. Although the bacteria have several virulence factors that lead to clinical symptoms, the organism, and not a specific toxin, mediates infection. A large inoculum is necessary to produce symptoms. Surveillance studies show that fewer than 5% of asymptomatic adults have positive stool cultures, and fecalľoral spread is not common. Typical symptoms, including fever, are as described in the case above. Patients with isolated GI illness do not require antibiotics.
IV-69. The answer is B. (Chap. 139) Listeria bacteremia in pregnancy is a relatively rare but serious infection both for the mother and fetus. Vertical transmission may occur, with 70% to 90% of fetuses developing infection from their mothers. Preterm labor is common. Prepartum treatment of the mother
increases the chances of a healthy delivery. Mortality among fetuses approaches 50% and is much lower in neonates receiving appropriate antibiotics. First-line therapy is with ampicillin, with gentamicin often added for synergy. This recommendation is the same for the mother and child. In patients with true penicillin allergy, the therapy of choice is trimethoprimľsulfamethoxazole. There are case reports of successful therapy with vancomycin, imipenem, linezolid, and macrolides, but there is not enough clinical evidence, and there have been some reports of failure that maintain ampicillin as recommended therapy.
IV-70. The answer is D. (Chap. 140) Tetanus is an acute disease manifested by skeletal muscle spasm and autonomic nervous system disturbance. It is caused by a powerful neurotoxin produced by the bacterium Clostridium tetani and is now a rare disease because of widespread vaccination. There were fewer than 50 cases reported recently in the United States, but there is a rising frequency in drug users. Older patients may be at higher risk because of waning immunity. The differential diagnosis of a patient presenting with tetanus includes strychnine poisoning and drug-related dystonic reactions. The diagnosis is clinical. Cardiovascular instability is common because of autonomic dysfunction and is manifest by rapid fluctuation in heart rate and blood pressure. Wound culture results are positive in approximately 20% of cases. Metronidazole or penicillin should be administered to clear infection. Tetanus immune globulin is recommended over equine antiserum because of a lower risk of anaphylactic reactions. Recent evidence suggests that intrathecal administration is efficacious in inhibiting disease progression and improving outcomes. Muscle spasms may be treated with sedative drugs. With effective supportive care and often respiratory support, muscle function recovers after clearing the toxin with no residual damage.
IV-71. The answer is B. (Chap. 141) This patient most likely has wound botulism. The use of ôblack-tarö heroin has been identified as a risk factor for this form of botulism. Typically, the wound appears benign, and unlike in other forms of botulism, gastrointestinal symptoms are absent. Symmetric descending paralysis suggests botulism, as does cranial nerve involvement. This patientĺs ptosis, diplopia, dysarthria, dysphagia, lack of fevers, normal reflexes, and lack of sensory deficits are all suggestive. Botulism can be easily confused with Guillain-Barré syndrome (GBS), which is often characterized by an antecedent infection and rapid, symmetric ascending paralysis and treated with plasmapheresis. The Miller Fischer variant of GBS is known for cranial nerve involvement with ophthalmoplegia, ataxia, and areflexia being the most prominent features. Elevated protein in the cerebrospinal fluid also favors GBS over botulism. Both botulism and GBS can progress to respiratory failure, so making a diagnosis by physical examination is critical. Other diagnostic modalities that may be helpful are wound culture, serum assay for toxin, and examination for decreased compound muscle action potentials on routine nerve stimulation studies. Patients with botulism are at risk of respiratory failure caused by respiratory muscle weakness or aspiration. They should be followed closely with oxygen saturation monitoring and serial measurement of forced vital capacity.
IV-72. The answer is E. (Chap. 142) Clostridia are gram-positive, spore-forming obligate anaerobes that reside normally in the gastrointestinal (GI) tract. Several clostridial species can cause severe disease. Clostridium perfringens, which is the second most common clostridial species to normally colonize the GI tract, is associated with food poisoning, gas gangrene, and myonecrosis. C. septicum is seen often in conjunction with GI tumors. C. sordellii is associated with septic abortions. All can cause a fulminant overwhelming bacteremia, but this condition is rare. The fact that this patient is well
several days after his acute complaints rules out this fulminant course. A more common scenario is transient, self-limited bacteremia caused by transient gut translocation during an episode of gastroenteritis. There is no need to treat when this occurs, and no further workup is necessary. Clostridium spp. sepsis rarely causes endocarditis because overwhelming disseminated intravascular coagulation and death occur so rapidly. Screening for GI tumor is warranted when C. septicum is cultured from the blood or a deep wound infection.
IV-73. The answer is A. (Chap. 143) Neisseria meningitidis is an effective colonizer of the human nasopharynx, with asymptomatic infection rates of greater than 25% described in some series of adolescents and young adults and among residents of crowded communities. Despite the high rates of carriage among adolescents and young adults, only 10% of adults carry meningococci, and colonization is very rare in early childhood. Colonization should be considered the normal state of meningococcal infection. Meningeal pharyngitis rarely occurs. Meningococcal disease occurs when a virulent form of the organism invades a susceptible host. The most important bacterial virulence factor relates to the presence of the capsule. Unencapsulated forms of N. meningitides rarely cause disease. A nonblanching petechial or purpuric rash occurs in more than 80% of cases of meningococcal disease. Of patients with meningococcal disease, 30% to 50% present with meningitis, approximately 40% with meningitis plus septicemia, and 20% with septicemia alone. Patients with complement deficiency, who are at highest risk of developing meningococcal disease, may develop chronic meningitis.