Burke A. Cunha

The atypical pneumonias: clinical diagnosis and importance

ABSTRACT The most common atypical pneumonias are caused by three zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and three non-zoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical CAPs by the pattern of extrapulmonary organ involvement which is characteristic for each atypical CAP. Zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history. The commonest clinical problem is to differentiate legionnaires disease from typical CAP as well as from C. pneumoniae or M. pneumonia infection. Legionella is the most important atypical pathogen in terms of severity. It may be clinically differentiated from typical CAP and other atypical pathogens by the use of a weighted point system of syndromic diagnosis based on the characteristic pattern of extrapulmonary features. Because legionnaires disease often presents as severe CAP, a presumptive diagnosis of Legionella should prompt specific testing and empirical anti-Legionella therapy such as the Winthrop-University Hospital Infectious Disease Divisions weighted point score system. Most atypical pathogens are difficult or dangerous to isolate and a definitive laboratory diagnosis is usually based on indirect, i.e., direct flourescent antibody (DFA), indirect flourescent antibody (IFA). Atypical CAP is virtually always monomicrobial; increased IFA IgG tests indicate past exposure and not concurrent infection. Anti-Legionella antibiotics include macrolides, doxycycline, rifampin, quinolones, and telithromycin. The drugs with the highest level of anti-Legionella activity are quinolones and telithromycin. Therapy is usually continued for 2 weeks if potent anti-Legionella drugs are used. In adults, M. pneumoniae and C. pneumoniae my exacerbate or cause asthma. The importance of the atypical pneumonias is not related to their frequency (~15% of CAPs), but to difficulties in their diagnosis, and their nonresponsiveness to β-lactam therapy. Because of the potential role of C. pneumoniae in coronary artery disease and multiple sclerosis (MS), and the role of M. pneumoniae and C. pneumoniae in causing or exacerbating asthma, atypical CAPs also have public health importance.

ANTIBIOTIC SIDE EFFECTS

Antibiotic side effects are approached best from an individual agent perspective rather than from a class-related standpoint. As this article indicates, with the exception of drug fevers and drug rashes, most antibiotic side effects are related to individual agents and not class side effects. Clinicians should view antimicrobial side effects as related to each organ system and be aware that more often a nonmicrobial medication is the explanation for the drug side effect rather than the antimicrobial. Nonantimicrobial medications are the most common cause of drug fever; among antimicrobials, beta-lactams and sulfonamides are the most common causes of drug-induced fevers. Antimicrobial side effects have important implications for the patient, legal and economic implications for the hospital, and medicolegal implications for the physician. Antibiotic side effects that prolong hospitalization in todays managed care environment have important economic implications. Clinicians should be familiar with the most common side effects of the most frequently used antimicrobials, to minimize the potential of having adverse reactions occur in patients. Most adverse events related to antimicrobials are reversible rapidly on cessation of the medication. Irreversible toxicities include aminoglycoside-induced ototoxicity, Stevens-Johnson syndrome, and toxicity secondary to nitrofurantoin. The most common acute fatal drug reactions include hypersensitivity reactions resulting in anaphylaxis or the Stevens-Johnson syndrome and fatal hepatic necrosis secondary to trovafloxacin. Clinicians should eliminate the use of drugs associated with chronic or fatal toxicities because multiple therapeutic alternatives exist for virtually every potential infection.

Third generation cephalosporins.

Third-generation cephalosporins are broad-spectrum antimicrobial agents useful in a variety of clinical situations. No one cephalosporin is appropriate for all infectious disease problems. Cefotaxime and ceftizoxime have the best gram-positive coverage of the third-generation agents. Ceftazidime and cefoperazone are the only third-generation drugs that provide antipseudomonal coverage. Ceftriaxones long half-life allows for once-daily dosing, making ceftriaxone an excellent drug for outpatient antibiotic therapy of community-acquired infections. Ceftriaxone is also useful for the treatment of Lyme disease and sexually transmitted diseases. The third-generation cephalosporins except for cefoperazone penetrate cerebrospinal fluid and are indicated for the treatment of bacterial meningitis. Their proven record of clinical efficacy, favorable pharmacokinetics, and low frequency of adverse effects make third-generation cephalosporins the preferred antibiotic in many clinical situations.

Influenza: historical aspects of epidemics and pandemics

Influenza is a zoonotic respiratory virus that affects birds, mammals, and humans. Influenza viruses are unique in their genetic instability, which frequently results in antigenic drift or shift. Antigenic shifts are responsible for influenza epidemics. Influenza A pandemics have been responsible for millions of deaths during the past several hundred years. In terms of virulence and lethality, the 1918 to 1919 influenza pandemic was the worst in history. It was unique in its predilection and lethality among young healthy adults. There has never been a satisfactory explanation for the unusual virulence of the 1918 to 1919 pandemic.

Osteomyelitis in Elderly Patients

In elderly persons, osteomyelitis is second only to soft-tissue infection as the most important musculoskeletal infection. Acute osteomyelitis is usually acquired hematogenously, and the most common pathogen is Staphylococcus aureus. Acute osteomyelitis can usually be cured with antimicrobial therapy alone. In contrast, chronic osteomyelitis may be caused by S. aureus but is often due to gram-negative organisms. The causative organism of chronic osteomyelitis is identified by culture of aseptically obtained bone biopsy specimens. Because of the presence of infected bone fragments without a blood supply (sequestra), cure of chronic osteomyelitis with antibiotic therapy alone is rarely, if ever, possible. Adequate surgical debridement is the cornerstone of therapy for chronic osteomyelitis, and cure is not possible without the removal of all infected bone.

Diagnostic Importance of Relative Lymphopenia as a Marker of Swine Influenza (H1N1) in Adults

NOTE. The rapid influenza test was QuickS Influ A/B kit (Denka Seiken). Among patients with complete blood counts, 25 adults and 16 children tested positive for influenza A, and 3 adults and 2 children tested positive for influenza B. in HIV-infected patients with tuberculosis. Clin Infect Dis 2007; 44:141–4. 10. Manosuthi W, Tantanathip P, Prasithisirikul W, Likanonsakul S, Sungkanuparph S. Durability of stavudine, lamivudine and nevirapine among advanced HIV-1 infected patients with/without prior co-administration of rifampicin: a 144-week prospective study. BMC Infect Dis 2008; 8:136.

Swine influenza (H1N1) pneumonia: clinical considerations.

Influenza is a viral zoonosis of birds and mammals that has probably existed since antiquity. Attack rates of influenza are relatively high but mortality is relatively low. Influenza mortality is highest in the very young, the very old, and the immunosuppressed. Influenza has the potential for rapid spread and may involve large populations. This article examines the swine influenza (H1N1) strain of recent origin, and compares the microbiology, epidemiology, clinical presentation, differential, clinical, and laboratory diagnosis, therapy, complications, and prognosis with previous recorded outbreaks of avian and human seasonal influenza pneumonias.

ANTIBIOTIC RESISTANCE: Control Strategies

Antibiotic resistance is a worldwide concern. Over the past several decades, antibiotic resistance has increased to many respiratory pathogens as well as aerobic gram-negative bacilli. Recently, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have become important hospital pathogens. Antibiotic resistance is not related to a particular antibiotic structure and is not dependent upon mechanism of antibiotic action. The volume of use per se does not increase antimicrobial resistance. This article discusses control strategies and identifies which antibiotics are associated with the emergence of resistant organisms.

NOSOCOMIAL PNEUMONIA: Diagnostic and Therapeutic Considerations

Many patients with presumed nosocomial pneumonia probably have infiltrates on the chest radiograph, fever, and leukocytosis resulting from noninfectious causes. Because of the high mortality and morbidity associated with nosocomial pneumonias, however, most clinicians treat such patients with a 2-week empiric trial of antibiotics. Before therapy is initiated, the clinician should rule out other causes of pulmonary infiltrates, fever, and leukocytosis that mimic a nosocomial pneumonia (e.g., pre-existing interstitial lung disease, primary or metastatic lung carcinomas, pulmonary emboli, pulmonary drug reactions, pulmonary hemorrhage, collagen vascular disease affecting the lungs, or congestive heart failure). If these disorders can be eliminated from diagnostic consideration, a 2-week trial of empiric monotherapy is indicated. The clinician should treat cases of presumed nosocomial pneumonia as if P. aeruginosa were the pathogen. Although P. aeruginosa is not the most common cause of nosocomial pneumonia, it is the most virulent pulmonary pathogen associated with nosocomial pneumonia. Coverage directed against P. aeruginosa is effective against all other aerobic gram-negative bacillary pathogens causing hospital-acquired pneumonia. The clinician should select an antibiotic for empiric monotherapy that is highly effective against P. aeruginosa, has a good side-effect profile, has a low resistance potential, and is relatively inexpensive in terms of its cost to the institution. The preferred agents for empiric monotherapy for nosocomial pneumonia are cefepime, meropenem, and piperacillin. Single organisms are responsible for nosocomial pneumonia, not multiple pathogens. S. aureus rarely, if ever, causes nosocomial pneumonia but is mentioned frequently in studies based on cultures of respiratory tract secretions. S. aureus, unless accompanied by a necrotizing pneumonia with rapid cavitation within 72 hours, in the sputum indicates colonization rather than infection and should not be addressed therapeutically. Antibiotics associated with a high resistance potential should not be used as monotherapy or included in combination therapy regimens (i.e., ceftazidime, ciprofloxacin, imipenem, or gentamicin). Combination therapy is more expensive than monotherapy and is indicated only when P. aeruginosa is extremely likely, based on its characteristic clinical presentation, or is proved by tissue biopsy. Therapy should not be based on respiratory secretion cultures regardless of technique. Optimal combination regimens include cefepime or meropenem plus levofloxacin or piperacillin or aztreonam or amikacin. Nosocomial pneumonias usually are treated for 14 days. Lack of radiographic or clinical response to appropriate empiric nosocomial pneumonia monotherapy after 14 days suggests an alternate diagnosis. In these patients, a tissue biopsy specimen should be obtained to determine the cause of the persistence of pulmonary infiltrates unresponsive to appropriate antimicrobial therapy.

THE CLINICAL SIGNIFICANCE OF FEVER PATTERNS

The clinical validity of fever curves remains intact. Clinicians of old were not wrong in their astute observations. The diagnostic usefulness of fever curves is best applied to difficult-to-diagnose infectious diseases where present day investigations are relatively unhelpful. Fever patterns are particularly useful in eliminating diagnoses from consideration and suggesting otherwise unsuspected disorders that may be diagnosed by further procedures.