The management of infectious diseases requires an understanding of the presenting clinical manifestations and knowledge of microbiology. Many infections present with constellations of focal and systemic signs and symptoms that in typical cases are highly suggestive of the diagnosis, though the disease might be caused by any of several different organisms. Making a clinical diagnosis with subsequent laboratory confirmation is part of the art of medicine. This chapter presents 24 cases and brief discussions of the differential diagnosis and management of those infections.

The reader is referred to earlier chapters of this book for characterizations of the organisms; to Chapter 47 for information about diagnostic microbiology tests; and to textbooks of medicine and infectious diseases for more complete information about the clinical entities.

Clinical Features

Temperature was 39.5°C, pulse 130/min, and respirations 24/min. Blood pressure was 110/60 mm Hg.

Physical examination showed a well-developed and well-nourished child of normal height and weight who was somnolent. When her neck was passively flexed, her legs also flexed (positive Brudzinski sign, suggesting irritation of the meninges). Ophthalmoscopic examination showed no papilledema, indicating that there had been no long-term increase in intracranial pressure. The remainder of her physical examination was normal.

Laboratory Findings

Minutes later, blood was obtained for culture and other laboratory tests, and an intravenous line was placed. Lumbar puncture was performed less than 30 minutes after the patient arrived in the emergency room. The opening pressure was 350 mm of cerebrospinal fluid (CSF) (elevated). The fluid was cloudy. Several tubes of CSF were collected for culture, cell counts, and chemistry tests. One tube was taken immediately to the laboratory for Gram staining. The stain showed many polymorphonuclear (PMN) cells with cell-associated (intracellular) gram-negative diplococci suggestive of Neisseria meningitidis (Chapter 20).

Blood chemistry tests were normal. The hematocrit was normal. The white blood cell count was 25,000/μL (markedly elevated), with 88% PMN forms and an absolute PMN count of 22,000/μL (markedly elevated), 6% lymphocytes, and 6% monocytes. The CSF had 5000 PMNs/μL (normal, 0–5 lymphocytes/μL). The CSF protein was 100 mg/dL (elevated), and the glucose was 15 mg/dL (low, termed hypoglycorrhachia)—all consistent with bacterial meningitis. Cultures of blood and CSF grew serogroup B N meningitidis.

Treatment

Intravenous cefotaxime therapy was started within 35–40 minutes of the patient’s arrival; dexamethasone was also given. The patient responded quickly and was treated with the antibiotic for 7 days. She recovered without obvious sequelae. Further neurologic examinations and hearing tests were planned for the future. Rifampin prophylaxis was given to the other children who attended the day care center.

Comment

Clinical features of bacterial meningitis vary with the age of the patient. In the older child and the adult, bacterial meningitis usually presents with fever, headache, vomiting, photophobia, altered mental status ranging from sleepiness to coma, and neurologic signs ranging from abnormalities of cranial nerve function to seizures. However, subtle signs such as fever and lethargy are consistent with meningitis, particularly in infants. Meningitis is considered to be acute with signs and symptoms of less than 24 hours’ duration and subacute when signs and symptoms have been present for 1–7 days. Lumbar puncture with examination of the CSF is indicated whenever there is any suspicion of meningitis.

Acute meningitis is most often caused by bacteria of a few species (Table 48-1): Lancefield serogroup B streptococci (Streptococcus agalactiae) (Chapter 14) and Escherichia coli (Chapter 15) in neonates; Haemophilus influenzae (Chapter 18) in unvaccinated children between the ages of 6 months and 6 years; N meningitidis in children and unvaccinated adolescents and young adults; and Streptococcus pneumoniae (Chapter 14) occasionally in children and increasing in incidence in middle-aged and elderly persons. Many other species of microorganisms less commonly cause meningitis. Listeria monocytogenes (Chapter 12) causes meningitis in immunosuppressed patients and normal persons. The yeast Cryptococcus neoformans (Chapter 45) is the most common cause of meningitis in AIDS patients and can cause meningitis also in other immunosuppressed patients as well as in normal persons. Meningitis due to Listeria or Cryptococcus can be acute or insidious in onset. Gram-negative bacilli cause meningitis in acute head trauma and neurosurgical patients and neonates (encapsulated E coli). S pneumoniae is found in recurrent meningitis in patients with basilar skull fractures. Mycobacterium tuberculosis (Chapter 23) can have a slow onset (chronic; >7 days) in immunologically normal persons but progresses more rapidly (subacute) in immunosuppressed persons such as AIDS patients. Naegleria species (Chapter 46), free-living amoebas, occasionally cause meningitis in persons with a recent history of swimming in warm fresh water. Viruses (Chapters 30, 33, 36) usually cause milder meningitis than bacteria. The viruses that most commonly cause meningitis are the enteroviruses (echoviruses and coxsackieviruses) and mumps virus.

The diagnosis of meningitis requires a high degree of suspicion when appropriate signs and symptoms are observed plus lumbar puncture without delay followed by examination of CSF. Findings in the spinal fluid typically include white blood cells in hundreds to thousands per microliter (PMNs for acute bacterial meningitis and lymphocytes for tuberculous and viral meningitis); glucose of less than 40 mg/dL, or less than 50% of the serum concentration; and protein of more than 100 mg/dL (Table 48-2). In bacterial meningitis, Gram stain of cytocentrifuged sediment of CSF shows PMNs and bacterial morphology consistent with the species subsequently cultured: N meningitidis, intracellular gram-negative diplococci; H influenzae, small gram-negative coccobacilli; and serogroup B streptococci and pneumococci, gram-positive cocci in pairs and chains. Blood cultures should be done along with the CSF cultures.

Acute bacterial meningitis is fatal if untreated. Initial therapy for bacterial meningitis in infants less than 1 month of age should consist of parenteral therapy known to be effective against the pathogens listed in Table 48-1 and including L monocytogenes. Ampicillin plus cefotaxime or ceftriaxone with or without gentamicin or ampicillin in combination with an aminoglycoside is recommended. For children between the ages of 1 month and 18 years of age and for the adult older than 50 years, the recommended therapies are vancomycin plus a third-generation cephalosporin because of the prevalence of multidrug-resistant S pneumoniae, reports of rising minimum inhibitory concentrations to penicillin among meningococci, and the prevalence of β-lactamase production among H influenzae. Since adults older than 50 years are also susceptible to L monocytogenes, the addition of ampicillin to the regimen for older children and adults as listed earlier is recommended.

Available evidence supports administration of adjunctive dexamethasone 10–20 minutes prior to or concomitant with the first antimicrobial dose to children with H influenzae meningitis and in the adult with pneumococcal meningitis with continuation of steroids for the first 2–4 days of therapy.

Several vaccines are currently available and are recommended for the prevention of the more serious causes of bacterial meningitis. The H influenzae type B conjugate vaccine and the 13-valent conjugate pneumococcal vaccine are currently part of the routine vaccination series for infants and young children. The 23-valent polysaccharide pneumococcal vaccine is recommended for prevention of invasive pneumococcal disease in certain high-risk groups older than 2 years. These include patients who are elderly and patients who have chronic underlying diseases such as cardiovascular disease, diabetes mellitus, chronic pulmonary problems, CSF leaks, and asplenia, among others. Vaccination with one of two available quadrivalent conjugated meningococcal vaccines is currently recommended for all healthy adolescents 11 or 12 years of age with a booster dose at age 16 and for 2- to 55-year-old persons at risk such as travelers to endemic areas, asplenic patients and patients with complement deficiencies. For adults older than 55, the meningococcal polysaccharide vaccine is currently recommended pending evaluation of the conjugate vaccine in this age group.

REFERENCES

Clinical Features

The temperature was 37°C, the pulse 110/min, and respirations 18/min. The blood pressure was 140/80 mm Hg.

On physical examination, the patient was sleepy and had a decreased attention span. He moved all his extremities, though the right arm moved less than the left. There was slight blurring of the left optic disk, suggesting possible increased intracranial pressure. The remainder of his physical examination was normal.

Laboratory Findings and Imaging

Laboratory tests were all normal, including hemoglobin and hematocrit, white blood cell count and differential, serum electrolytes, blood urea nitrogen, serum creatinine, urinalysis, chest x-ray, and electrocardiogram (ECG). Lumbar puncture was not done and cerebrospinal fluid was not examined because of possible increased intracranial pressure due to a mass lesion. Blood cultures were negative. Computed tomography (CT) scan with contrast enhancement of the patient’s head showed a 1.5-cm localized ring-enhancing lesion in the left parietal hemisphere suggestive of a brain abscess.

Treatment

The patient had a neurosurgical procedure with complete drainage of the lesion. Culture of necrotic material from the lesion yielded Prevotella melaninogenica (Chapter 21) and Streptococcus anginosus (Chapter 14). Pathologic examination of the tissue suggested that the lesion was several weeks old. The patient received antibiotic therapy for 6 weeks. He had no more seizures and no subsequent neurologic deficits. One year later, anticonvulsant medications were discontinued and a follow-up CT scan was negative.

Comment

A brain abscess is a localized pyogenic bacterial infection within the brain parenchyma. The major clinical manifestations are related to the presence of a space-occupying mass in the brain rather than the classic signs and symptoms of infection. Thus, patients commonly present with headache and a change in mental status from normal to lethargy or coma. Focal neurologic findings related to location of the abscess occur in less than half of patients; one-third have seizures, and less than half have fever. Occasionally, patients present with signs and symptoms suggesting acute meningitis. Initially, the clinician must differentiate brain abscess from other central nervous system processes, including primary or metastatic cancers, subdural or epidural abscesses, meningitis, stroke, and a variety of other diseases.

Significant predisposing factors for brain abscess include distant site infections with bacteremia, such as endocarditis, lung infections, or other occult infections. Brain abscess can also occur via spread from contiguous sites of infection such as in the middle ear, mastoid, sinuses, from dental infections or recent dental work. Disruption of protective barriers as in the case of neurosurgery or following penetrating trauma is another factor. Finally, immunosuppressive agents or immunocompromising conditions such as HIV are also important. However, 20% of patients with brain abscesses have no discernible predisposing factors.

Brain abscess can be caused by a single species of bacteria, but more often infections are polymicrobial. Of the facultative and aerobic bacteria, the viridans streptococci (including nonhemolytic and α- and β-hemolytic strains, the S anginosus group, Streptococcus mitis, etc; see Chapter 14) are most common, occurring in one-third to one-half of patients. Staphylococcus aureus (Chapter 13) is isolated in 10–15% and, when present, is often the only isolate found. Enteric gram-negative rods occur in about 25%, often in mixed cultures. Many other facultative or aerobic bacteria (eg, S pneumoniae, Nocardia sp., M tuberculosis and nontuberculous Mycobacteria) also occur in brain abscesses. Anaerobic bacteria are found in 50% or more of cases (Chapter 21). Peptostreptococcus is most common, followed by Bacteroides and Prevotella species. Fusobacterium, Actinomyces, and Eubacterium are less common, followed by other anaerobes. Fungi (Chapter 45) are seen almost exclusively in immunocompromised patients. Candida species are the most prevalent fungi, but opportunistic molds such as Aspergillus sp. and Scedosporium apiospermum are increasing in frequency. Dimorphic fungi such as Coccidioides immitis may also cause brain abscesses. C neoformans is an important pathogen in AIDS patients. Parasites (Chapter 46) responsible for brain abscesses include Toxoplasma gondii, the most common protozoan cause, particularly among AIDS patients, neurocysticercosis (larval form of Taenia solium), Entamoeba histolytica, Schistosoma sp., and Paragonimus.

Lumbar puncture to obtain CSF is generally not indicated in patients with brain abscess (or other mass lesions in the brain). The increased intracranial pressure makes the procedure life threatening, because herniation of the brain through the tentorium cerebelli can result in midbrain compression. The findings in CSF are not specific for brain abscess: White blood cells, predominantly mononuclear cells, are often present; the glucose level may be moderately low and the protein concentration elevated. Thus, when fever and signs suggesting acute meningitis are absent and brain abscess is suspected, the clinician should obtain a CT scan with contrast enhancement. Brain abscesses typically show ring-enhanced uptake of contrast material on CT scan, though similar findings can be found in patients with brain tumors and other diseases. Magnetic resonance imaging (MRI) may be helpful in differentiating brain abscesses from tumors. Definitive differentiation between brain abscess and tumor is done by pathologic examination and culture of tissue from the lesion obtained by a neurosurgical procedure.

Untreated brain abscesses are fatal. Surgical excision provides the initial therapy as well as the diagnosis of brain abscess. Needle aspiration using stereotactic technique is an alternative to surgical excision. Antibiotic therapy should be parenteral and should include high-dose penicillin G for streptococci and many anaerobes, metronidazole for anaerobes resistant to penicillin G, plus a third-generation cephalosporin for enteric gram-negative rods. Vancomycin or another drug specific for S aureus should be included in the initial therapy if the patient has endocarditis or is known to have staphylococcal bacteremia, or the abscess yields staphylococci. Initial therapy with antibiotics rather than surgery can be instituted in some patients whose brain abscesses are small (<2 cm), multiple, or difficult to reach surgically, but deteriorating neurologic functions indicate the need for surgery. Once culture results from the abscess material are known, initial antibiotic therapy should be modified to be specific for the bacteria, fungus, or parasite isolated from the lesion. Antibiotic therapy should be continued for at least 3–4 weeks when surgical excision has been done or for 8 weeks or longer when there has been no surgery. Nonbacterial causes of brain abscesses generally require definitive diagnoses and specific therapy of possibly longer duration. Steroids to decrease swelling should be used only when there is mass effect.

REFERENCES

Clinical Features

Temperature was 39°C, pulse 130/min, and respirations 28/min. Blood pressure was 120/80 mm Hg.

Physical examination showed a slightly overweight man who was coughing frequently and holding his left chest when he coughed. He produced very little thick rust-colored sputum. His chest examination showed normal movement of the diaphragm. There was dullness to percussion of the left lateral posterior chest, suggesting consolidation of the lung. Tubular (bronchial) breath sounds were heard in the same area along with dry crepitant sounds (rales), consistent with lung consolidation and viscous mucus in the airway. The remainder of his physical examination was normal.

Laboratory Findings and Imaging

Chest films showed a dense left lower lobe consolidation consistent with bacterial pneumonia. The hematocrit was 45% (normal). The white blood cell count was 16,000/μL (markedly elevated) with 80% PMN forms with an absolute PMN count of 12,800/μL (markedly elevated), 12% lymphocytes, and 8% monocytes. Blood chemistry tests, including electrolytes, were normal. Sputum was thick, yellow to rust colored, and purulent in appearance. Gram stain of the sputum showed many PMN cells and lancet-shaped gram-positive diplococci. Twenty-four hours later, the blood cultures were positive for S pneumoniae (Chapter 14). Cultures of sputum grew numerous S pneumoniae and a few colonies of H influenzae (Chapter 18).

Treatment

The initial diagnosis was bacterial pneumonia, probably pneumococcal. Parenteral aqueous penicillin G therapy was begun on the basis of local data which showed little penicillin resistance among pneumococci, and the patient was given parenteral fluids. Within 48 hours, his temperature was normal and he was coughing up large amounts of purulent sputum. Penicillin G was continued for 7 days. At follow-up 4 weeks after admission to the hospital, the lung consolidation had cleared.

Clinical Features

The temperature was 39°C, pulse 110/min, and respirations 30/min. Blood pressure was 115/70 mm Hg. The patient appeared to be acutely uncomfortable. He had a skin rash consisting of multiple crops or stages of lesions ranging from red maculopapules to vesicles that were broken and crusted over. His fingers and lips appeared to be slightly blue. Rales were heard bilaterally throughout both lung fields. The remainder of the physical examination was normal.

Laboratory Findings and Imaging

Chest films showed diffuse bilateral interstitial pulmonary infiltrates. Arterial blood gases showed a PO₂ of 60 mm Hg with 91% hemoglobin saturation. The hematocrit, white blood cell count, and serum electrolytes and liver tests were normal.

Treatment and Hospital Course

The patient was hospitalized and placed on oxygen therapy, which improved his hypoxia. He was given high-dose intravenous acyclovir. Over the next several days, his respiratory status improved, and on day 6, oxygen therapy was discontinued. The acyclovir was changed to oral therapy on day 3 and continued for a total of 10 days. The patient was discharged to home care on day 7.

Comment

Acute bacterial pneumonia commonly presents with an abrupt onset of chills and fever, cough, and often pleuritic chest pain. The cough frequently is productive of purulent sputum, but many patients with pneumonia are not adequately hydrated and do not produce sputum until they receive fluids, as in this case. Pleuritic chest pain occurs when the inflammatory process of the pneumonia involves the pleural lining of the lung and chest cavity; movement of the pleura, as occurs with coughing or deep breathing, yields localized pain. Patients with acute pneumonia appear ill and usually have tachypnea (rapid breathing) and tachycardia (rapid heart rate). Many patients with pneumonia have predisposing factors (congestive heart failure, chronic obstructive pulmonary disease, etc), which become exacerbated before or in association with the pneumonia.

The findings on physical examination are those associated with consolidation of the lung tissue, purulent mucus (sputum) in the airway, and, in some patients, fluid in the chest cavity. On percussion, there is dullness over the area of consolidation (or fluid). When consolidation occurs, the small airways are closed, leaving only the large airways open; on auscultation, there are tubular breath sounds over the area. If all the airways are blocked, no breath sounds are audible. Dry crepitant sounds (rales) or crackling sounds on auscultation indicate fluid or mucus in the airways; these sounds may change when the patient coughs.

Viral pneumonia is characterized by interstitial inflammation of the lung tissue and hyaline membrane formation in the alveolar spaces, often accompanied by bronchiolitis and sloughing of the ciliated cells of the small airways with peribronchial inflammation. The viruses that most commonly cause pneumonia are respiratory syncytial virus, parainfluenza viruses (typically type 3), influenza viruses, adenoviruses, measles virus, and varicella-zoster virus (Chapters 32, 39, 40). Cytomegalovirus (Chapter 33) causes pneumonia in allogeneic bone marrow and solid organ transplant patients; varicella-zoster virus may cause pneumonia in these patients as well. Emerging viral pathogens such as Metapneumovirus and newly discovered Coronaviruses such as MERS-Coronavirus (case 23) may cause disease that mimics that of the more common viral respiratory pathogens (Chapters 40, 41). SARS Coronavirus was responsible for epidemic fatal respiratory disease in several countries (case 20). Many other infectious agents (and noninfectious agents also) can cause interstitial pneumonitis with or without focal consolidation in the lung. Examples include Legionella pneumophila (Chapter 22), Mycoplasma pneumoniae (Chapter 25), and Pneumocystis jirovecii (Chapter 45). The physical findings on chest examination in viral pneumonia frequently are limited; often only rales are heard on auscultation. Some of the viruses cause characteristic rashes that may serve as clues to diagnosis. Chest films show diffuse bilateral interstitial infiltrates. Focal areas of consolidation may be present. Supportive care such as oxygen therapy and specific antiviral chemotherapy, when possible, are important.

Community acquired pneumonia (CAP) is defined as an acute infection of the lungs in persons not recently hospitalized or otherwise exposed to a heath care facility. The most common causes of CAP are S pneumoniae (Chapter 14), H influenzae (Chapter 18), Moraxella catarrhalis (Chapter 16), S aureus (Chapter 13), and less commonly, certain gram-negative bacilli, the latter occurring more frequently in patients with chronic lung disease. Data on the frequency of “atypical” pathogens, namely M pneumoniae (Chapter 25), L pneumophila (Chapter 22), and Chlamydia pneumoniae (Chapter 27) varies (Table 48-3) but these should be considered when choosing empiric therapy regimens; Pleural pulmonary infections with mixed anaerobic bacteria are associated with predisposing factors such as periodontal disease, seizure disorders, stupor or coma, and aspiration of oropharyngeal bacteria into the lung. Pneumonia, lung abscesses, and infection of the pleural space (empyema, or pus in the chest cavity) occur with mixed anaerobic infections.

Health care–associated pneumonia (HCAP) is a category of infection created in 2005 to distinguish persons in the community with recent hospitalization, who reside in long-term care facilities, or who frequently have exposure to health care environments (such as hemodialysis clinics and who are at risk for acquisition of the same types of multidrug resistant pathogens that are seen among hospitalized patients [HAP] and patients who are on ventilator support [VAP]). The organisms responsible for these infections are quite different from the etiologies of CAP. HCAP, HAP, and VAP are frequently caused by multidrug-resistant enteric gram-negative bacilli such as E coli, Klebsiella pneumoniae, Enterobacter sp. (Chapter 15), and Pseudomonas aeruginosa (Chapter 16); S aureus (Chapter 13), and Legionella may also cause hospital-acquired pneumonia. Fungi, including Histoplasma capsulatum, C immitis, and C neoformans (Chapter 45), cause CAP; Candida and Aspergillus species (Chapter 45) are more likely to cause nosocomial infections.

Blood counts in patients with pneumonia usually show leukocytosis with increased PMN cells. Chest radiography shows segmental or lobar infiltrates. Cavities may be seen especially with mixed anaerobic infections or pneumonia due to S aureus or group A streptococci. Pleural effusions may also be found and, if present, may call for thoracentesis to obtain fluid for cell counts and culture and for therapeutic purposes in the case of empyema. Blood cultures should be done in all patients admitted to the hospital with acute pneumonia even though the yield is variable (eg, 20–25% with S pneumoniae, much less in disease caused by H influenzae). Sputum, when available, may be useful for Gram stain and culture as well.

Many patients with bacterial pneumonia and pneumonia due to other causes have mucopurulent sputum. Rust-colored sputum suggests alveolar involvement and is associated with pneumococcal pneumonia but occurs with other organisms also. Foul-smelling sputum suggests mixed anaerobic infection. A purulent portion of the sputum should be chosen for Gram stain and microscopic examination; an adequate sputum specimen will have over 25 PMN cells and fewer than 10 epithelial cells per low-power field (100× magnification). Traditionally, microscopic examination of the sputum has been used to help determine the cause of pneumonia; however, it may be difficult to differentiate organisms that are part of the normal oropharyngeal microbiota from those that are causing the pneumonia. The finding of numerous lancet-shaped gram-positive diplococci strongly suggests S pneumoniae, but streptococci that are part of the oropharyngeal microbiota can have the same appearance. The major value of stained sputum smears is when organisms that would not be expected are found (eg, numerous PMN cells along with numerous gram-negative bacilli suggesting enteric bacilli or Pseudomonas, or numerous gram-positive cocci in clusters suggesting staphylococci). Sputum cultures have many of the same drawbacks as smears; it may be difficult to differentiate normal microbiota or colonizing bacteria from the cause of the pneumonia.

True demonstration of the cause of pneumonia comes from a limited set of specimens: a positive blood culture in a pneumonia patient with no confounding infections; a positive pleural fluid or direct lung aspirate culture; and detection of circulating antigen of a specific organism with no confounding infection (eg, S pneumoniae or L pneumophila urinary antigen). Bronchoscopy is often used to obtain material for diagnostic studies in severely ill patients with pneumonia and is recommended for health care–associated pneumonia and pneumonia in the immunocompromised host. Quantitative bacterial culture performed on a carefully collected bronchoalveolar lavage (BAL) sample using 10⁴ colony-forming units (CFU)/mL of a specific pathogen per sample as the cutoff for clinical significance is useful for establishing an etiology of bacterial pneumonia in patients not previously treated with antibiotics. Bronchoscopy with BAL may also yield a nonbacterial pathogen such as a filamentous mold or viral pathogen in the at-risk patient.

Several commercially available multiplex nucleic acid amplification methods are now available to assist in the diagnosis of viral pneumonia and pneumonia caused by the atypical pathogens such as M pneumoniae and C pneumoniae. Other platforms specifically for the detection of CAP and HCAP are in development.

In the United States, several professional societies (see ATS and IDSA guidelines below) have established practice guidelines for the diagnosis and empirical and definitive treatment of community-acquired pneumonia and health care–associated and ventilator-associated pneumonia. For patients with community-acquired pneumonia, a macrolide, fluoroquinolone, or doxycycline is recommended as monotherapy for previously healthy outpatients. A macrolide plus a β-lactam or a fluoroquinolone alone is recommended for initial empiric treatment of outpatients in whom resistance is an issue and for patients who require hospitalization. A recent update by Musher et al (see References) suggests modifications to the guidelines for outpatient treatment because of the increases in macrolide and tetracycline resistance among common CAP organisms. In brief, amoxicillin-clavulanate with the addition of azithromycin, if Legionella is a concern, is suggested for outpatients. It is also recommended that fluoroquinolones such as levofloxacin or moxifloxacin be reserved for patients with predisposing lung disease or other comorbidities. These regimens should be modified in the event that an etiology is established and once the susceptibility of the causative agent is determined. In the case of HCAP, multidrug resistance is often a major problem, and targeted antipseudomonal therapy with third-generation cephalosporins, carbapenems, or β-lactam/β-lactamase inhibitor combinations with or without an aminoglycoside may be required. More recently, the increase in prevalence of multidrug-resistant organisms, such as carbapenem resistant K pneumoniae and Acinetobacter baumannii resistant to all antimicrobials except colistin, has challenged these recommendations and has contributed to increased mortality.

REFERENCES

Clinical Features

Temperature was 38°C, pulse 90/min, and respirations 18/min. Blood pressure was 130/80 mm Hg.

Physical examination showed a moderately overweight woman who was alert and oriented. She became short of breath while walking up two flights of stairs. Examination of her eyes showed a Roth spot (a round white spot surrounded by hemorrhage) in the retina of her right eye. Petechiae were seen in the conjunctiva of both eyes. Her head and neck were otherwise normal. Splinter hemorrhages were seen under two fingernails of her right hand and one finger of the left hand. Osler’s nodes (tender, small, raised, red or purple lesions of the skin) were seen in the pads of one finger and one toe. Her heart size was normal to percussion. On auscultation, a low-pitched diastolic murmur consistent with mitral valve stenosis was heard at the apex; a loud mitral valve opening snap was heard over the left chest. Examination of her abdomen was difficult because of obesity; one observer felt an enlarged spleen. The remainder of her physical examination was normal.

Laboratory Findings and Imaging

The films from a chest x-ray showed a normal heart size and normal lungs. The ECG showed a normal sinus rhythm with broad P waves (atrial conduction). Echocardiography showed an enlarged left atrium, thickened mitral valve leaflets, and a vegetation on the posterior leaflet. The hematocrit was 29% (low). The white blood cell count was 9800/μL (high normal), with 68% PMNs (high), 24% lymphocytes, and 8% monocytes. The erythrocyte sedimentation rate was 68 mm/h (high). Blood chemistry tests, including electrolytes and tests of renal function, were normal. Three blood cultures were obtained on the day of admission; 1 day later, all three were positive for gram-positive cocci in chains that were viridans streptococci and subsequently identified as Streptococcus sanguinis (Chapter 14).

Treatment

Endocarditis of the mitral valve was diagnosed. Intravenous penicillin G and gentamicin were begun and continued for 2 weeks. The patient was afebrile within 3 days after starting therapy. Following the successful treatment of her endocarditis, she was referred for long-term management of her heart disease.

Comment

The symptoms and signs of endocarditis are quite varied because any organ system can be secondarily (or primarily) involved. Fever occurs in 80–90% of patients, chills in 50%, anorexia and weight loss in about 25%, and skin lesions in about 25%. Nonspecific symptoms such as headache, backache, cough, and arthralgia are very common. Up to 25% of endocarditis patients present with neurologic signs or strokes secondary to emboli from heart valve vegetations. Backache, chest pain, and abdominal pain occur in 10–20% of the patients. Physical findings typically include fever in 90–95%, a heart murmur in 80–90% with a new or changing heart murmur in about 15%, and splenomegaly and skin lesions in about 50% of patients. Many other symptoms and physical findings are directly related to the complications of metastatic infection and embolization from vegetations.

Streptococci and staphylococci cause about 80% of endocarditis cases. Viridans streptococci of several species (eg, S sanguinis, Streptococcus salivarius, Streptococcus mutans, Streptococcus bovis group; Chapter 14) are most common, followed by enterococci (eg, Enterococcus faecalis) and other streptococci. The streptococci usually cause endocarditis on abnormal heart valves. The proportion of causes attributed to staphylococci is increasing due to the decline in cases associated with rheumatic heart disease and the increase in health care–associated infections. S aureus causes 20–25% of community acquired cases but a much higher proportion of health care–associated disease (see reference Hoen et al) and likewise Staphylococcus epidermidis about 5% of community and 15% of health care–associated cases (Chapter 13). S aureus can infect normal heart valves, is common in intravenous drug abusers and patients who acquire their disease in the hospital, and produces more rapidly progressive disease than the streptococci. S epidermidis is a cause of endocarditis on prosthetic valves and only rarely infects native valves. Gram-negative bacilli (Chapters 15, 18) occur in about 5% and yeasts such as Candida albicans in about 3% of cases (Chapter 45). Emerging pathogens such as Bartonella sp. (Chapter 22) and Tropheryma whipplei (Chapter 22) have been reported with increasing frequency. Many other bacteria—indeed any species—can cause endocarditis; a small percentage are culture negative.

The history and physical examination are important diagnostic procedures. The diagnosis is strongly suggested by repeatedly positive blood cultures with no other site of infection. Echocardiography can be a very helpful adjunctive procedure; the presence of vegetations in a patient with unexplained fever strongly suggests endocarditis.

Antibiotic therapy is essential because untreated endocarditis is fatal. Bactericidal drugs should be used. The choice of antibiotics depends on the infecting organism: Penicillin G plus gentamicin for 2 weeks for viridans streptococci and for 6 weeks for susceptible enterococci is recommended. Vancomycin is the drug of choice for penicillin-resistant strains. Multidrug resistance among enterococci may require the use of newer agents such as linezolid and daptomycin based on susceptibility data. S aureus is treated with a penicillinase-resistant penicillin (eg, nafcillin) often with the addition of gentamicin for the first 5 days of therapy. Vancomycin is substituted for the β-lactam in cases of methicillin/oxacillin-resistant staphylococci. Daptomycin is recommended for MRSA infections of the right side of the heart and may be useful for left-sided disease as well. Treatment duration for staphylococcal endocarditis is 6 weeks. Bacteria other than the streptococci and staphylococci are treated with antibiotics of demonstrated activity based on local antibiograms. Surgery with valve replacement is necessary when valvular regurgitation (eg, aortic regurgitation) results in acute heart failure even when active infection is present and to control infection unresponsive to medical treatment (as may occur with fungi and gram-negative pathogens). Contiguous spread of infection to the sinus of Valsalva or resultant abscesses, and prevention emboli due to large vegetations are other important indications for surgery.

REFERENCES

Clinical Features

The temperature was 38°C, the pulse 100/min, and respirations 24/min. The blood pressure was 110/70 mm Hg.

Physical examination showed a normally developed young man who appeared acutely ill and complained of diffuse abdominal pain. The chest and heart examinations were normal. The abdomen was slightly distended. There was diffuse periumbilical and right lower quadrant tenderness to palpation with guarding (muscle rigidity with palpation). There was a suggestion of a right lower quadrant mass. Bowel sounds were infrequent.

Laboratory Findings and Imaging

The hematocrit was 45% (normal), and the white blood cell count was 20,000/μL (markedly elevated) with 90% PMN cells (markedly elevated) and 12% lymphocytes. The serum amylase (a test for pancreatitis) was normal. Electrolytes and tests of liver and renal function were normal. X-ray films of the chest and abdomen were normal, though several distended loops of small bowel were seen. CT scan of the abdomen showed a fluid collection in the right lower quadrant with extension into the pelvis.

Treatment

The patient was taken to the operating room. At surgery, a perforated appendix with a large periappendiceal abscess extending into the pelvis was found. The appendix was removed, about 300 mL of foul-smelling abscess fluid was evacuated, and drains were placed. The patient was treated with ertapenem for 2 weeks. The drains were advanced daily and totally removed 1 week after surgery. Culture of the abscess fluid revealed at least six species of bacteria, including E coli (Chapter 15), Bacteroides fragilis (Chapter 21), viridans streptococci, and enterococci (normal gastrointestinal microbiota). The patient recovered uneventfully.

Comment

Pain is the usual primary manifestation of peritonitis and intra-abdominal abscess formation. The localization and intensity of the pain are related to the primary disease of the abdominal viscera. Perforation of a peptic ulcer quickly yields epigastric pain that rapidly spreads throughout the abdomen with the spillage of gastric contents. A ruptured appendix or sigmoid colon diverticulum often produces more localized right or left lower quadrant pain, respectively, associated with the focal peritonitis and abscess formation. Nausea, vomiting, anorexia, and fever accompany the pain.

The signs and symptoms following acute spillage of bowel contents into the abdomen tend to take two phases. The first is the peritonitis stage, with acute pain associated with infection by E coli and other facultative anaerobic bacteria; this occurs over the first 1–2 days and if untreated is associated with a high mortality rate. The second stage is abscess formation associated with infection with B fragilis and other obligately anaerobic bacteria.

Physical examination during the acute phase shows abdominal rigidity and diffuse or local tenderness. Often the tenderness is pronounced when palpation of the abdomen is released, termed rebound tenderness. Later, abdominal distention and loss of bowel motility (paralytic ileus) occur.

The bacteria that make up the normal gastrointestinal microbiota (Chapter 10) are the causes of acute peritonitis and abscesses associated with bowel rupture: E coli and other enteric gram-negative rods, enterococci, viridans streptococci, B fragilis and other anaerobic gram-negative rods, and anaerobic gram-positive cocci and rods of many species.

The history and physical examination are the important initial steps in the diagnosis, to determine the acuteness and localization of the problem. Laboratory tests, such as white blood cell counts, yield nonspecific abnormal results or help rule out diseases such as pancreatitis, as in this case. X-ray films of the abdomen are very useful diagnostic adjuncts and may show gas and fluid collections in the large and small bowel. More definitive information indicating focal abnormalities is obtained using contrast enhanced CT scans. When fluid is present, needle aspiration and culture yield a diagnosis of infection but do not define the underlying disease process.

Surgery may be necessary to obtain a definitive etiologic diagnosis, while at the same time it provides the definitive step in therapy. The underlying disease process, such as a gangrenous bowel or ruptured appendix, can be corrected and the localized infection drained. Antimicrobial drugs are important adjunctive therapy. The selection of drugs might include an antimicrobial active against enteric gram-negative rods, one active against the enterococci and streptococci, and a third against the anaerobic gram-negative rods that are often resistant to penicillin G. Many regimens have been described; one regimen includes gentamicin, ampicillin, and metronidazole; more recently piperacillin/tazobactam and ertapenem have supplanted triple-drug regimens.