Walter R. Wilson

Optimal Testing Parameters for Blood Cultures

The effects of volume of blood, number of consecutive cultures, and incubation time on pathogen recovery were evaluated for 37,568 blood cultures tested with the automated BACTEC 9240 instrument (Becton Dickinson Diagnostic Instrument Systems) at a tertiary care center over the period of 12 June 1996 through 12 October 1997. When the results for this study were compared with previous data published for manual broth-based blood culture systems and patient samples obtained in the 1970s and 1980s, the following were found: (1) the percentage increase in pathogen recovery per milliliter of blood is less, (2) more consecutive blood culture sets over a 24-h period are required to detect bloodstream pathogens, and (3) a shorter duration of incubation is required to diagnose bloodstream infections. Guidelines developed in the 1970s and 1980s for processing and culturing blood may require revision.

Risk Factor Analysis of Permanent Pacemaker Infection

Background. Several host- and procedure-related factors have been reported to increase the risk of permanent pacemaker (PPM) infection on the basis of descriptive analyses of case series. The purpose of this study is to assess the risk factors for PPM infection using case-control study methods.Methods. All patients who had a PPM implanted at our institution from January 1991 to December 2003 were retrospectively reviewed. Each patient who experienced a PPM infection was matched with 2 control subjects by age, sex, year of implantation, and duration of follow-up. Univariate and multivariable analyses were performed to identify significant risk factors for PPM infection.Results. Twenty-nine case patients and 58 control subjects met inclusion criteria. The majority (83%) of case patients presented with a pocket infection; a minority (10%) had PPM-related endocarditis. Staphylococcus species (69%) were the most common pathogens. On univariate analysis, previous PPM infection, malignancy, long-term corticosteroid use, multiple device revisions, a permanent central venous catheter, the presence of >2 pacing leads, and a lack of antibiotic prophylaxis at the time of PPM placement were associated with an increased risk of PPM infection. A multivariable logistic regression model identified long-term corticosteroid use (odds ratio [OR], 13.90; 95% confidence interval [CI], 1.27-151.7; P=.03) and the presence of >2 pacing leads versus 2 leads (OR, 5.41; 95% CI, 1.44-20.29; P=.01) as independent risk factors for PPM infection. In contrast, use of antibiotic prophylaxis prior to PPM implantation had a protective effect (OR, 0.087; 95% CI, 0.016-0.48; P=.005).Conclusions. These findings should assist clinicians in identifying patients who are at increased risk of PPM infection, as well as in developing strategies to minimize the modifiable risks.

Pulmonary disease in the immunocompromised host (first of two parts)

With few exceptions, pulmonary complications in the immunocompromised host will proceed to death unless the clinician intercedes. The differential diagnosis of diffuse pulmonary disease in this setting includes (1) infection, most commonly from opportunistic organisms; (2) recurrence or extension of the basic underlying disease process to involve the lungs; (3) adverse pulmonary reaction to drugs; (4) a new, unrelated disease process such as cardiac pulmonary edema or pulmonary emboli; and (5) any combination of these categories. Up to a third of these patients have two or more complications, such as pneumonitis from two different opportunistic organisms or an opportunistic infection and a drug-induced pulmonary complication. An understanding of the host defense that is compromised enables the clinician to narrow the differential diagnosis. The most common types of impairment of defense mechanisms are reductions in the number of granulocytes, B-lymphocytes, or T-lymphocytes, and not uncommonly, two or all three of these types of cells are involved. Impairment of each of these cell types is associated with an increased frequency of infection by a particular group of organisms. Consequently, the clinician can be somewhat selective if empiric therapy is being considered. In the immunocompromised patient, most pulmonary complications, including drug-induced pulmonary disease and pulmonary emboli, are associated with fever that mimics an infection. Up to 25% of the pulmonary complications in these patients are noninfectious.

Frequency of Permanent Pacemaker or Implantable Cardioverter-Defibrillator Infection in Patients with Gram-Negative Bacteremia

BACKGROUND Despite the frequent occurrence of bacteremia due to gram-negative organisms in patients with underlying permanent pacemakers (PPMs) or implantable cardioverter defibrillators (ICDs), the outcome and treatment of these patients has received scant attention. In patients with PPMs or ICDs who have Staphylococcus aureus bacteremia, 45% have PPM/ICD infection. METHODS We conducted a retrospective cohort study over a 7-year period to assess the clinical features and frequency of PPM/ICD infection in patients with gram-negative bacteremia, as well as the incidence of relapse in patients for whom the device was not removed. RESULTS Forty-nine patients were included in the study; 3 (6%) had either definite (2 patients) or possible (1 patient) PPM/ICD infection. Both patients with definite PPM/ICD infection had clear infection of the generator pocket. None of the other patients with alternate sources of bacteremia developed PPM/ICD infection. Thirty-four patients with retained PPM/ICD were observed for >12 weeks (median time, 759 days), and 2 (6%) developed relapsing bacteremia, although they each had alternative sources of relapse. CONCLUSIONS In sharp contrast to S. aureus infection, PPM/ICD infection in patients with gram-negative bacteremia was rare, and no patients appeared to have secondary PPM/ICD infection due to hematogenous seeding of the system. Despite infrequent system removal in these patients, relapsing bacteremia among patients who survived initial bacteremia was rarely seen. If secondary PPM/ICD infection occurs in patients with gram-negative bacteremia, it is either uncommon or it is cured with antimicrobial therapy despite device retention.

Impact of Prior Antiplatelet Therapy on Risk of Embolism in Infective Endocarditis

BACKGROUND Embolism is a dreaded complication of infective endocarditis (IE). Currently, antimicrobial therapy is the only medical intervention proven to decrease the risk of embolism associated with IE. We hypothesized that, because platelet aggregation is operative in the pathogenesis of vegetation formation, embolism associated with IE should occur less frequently among patients who have received prior, continuous daily antiplatelet therapy for noninfectious reasons. METHODS We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to the Mayo Clinic (Rochester, MN) during 1980-1998. The cohort was divided into 2 groups on the basis of whether they had received continuous daily antiplatelet therapy for at least 6 months prior to the time of hospitalization for IE. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine, or any of combination of these agents. The primary end point was a symptomatic embolic event that occurred prior to or during hospitalization. Multivariable logistic regression was used to assess the impact of continuous daily antiplatelet therapy on risk of symptomatic emboli associated with IE. RESULTS One hundred forty-seven (24.5%) of 600 patients experienced a symptomatic embolic event; the most common embolic manifestation was stroke (in 48.2% of patients). Embolic events occurred significantly less often among those who had received prior, continuous daily antiplatelet therapy (12.0% of patients who had received therapy vs. 27.8% patients who had not receive therapy; P<.001). After adjustment for several covariates known to influence both risk of embolism and propensity for antiplatelet use, the adjusted odds ratio for a symptomatic embolic event was 0.36 (95% confidence interval, 0.19-0.68; P=.002) for patients receiving continuous daily antiplatelet therapy. CONCLUSIONS The risk of symptomatic emboli associated with IE was reduced in patients who received continuous daily antiplatelet therapy before onset of IE.

Erythromycin: A Microbial and Clinical Perspective After 30 Years of Clinical Use (Second of Two Parts)

Erythromycin, first introduced for clinical use 30 years ago, was found to be effective for the treatment of gram-positive bacterial infections. Emergence of resistance and the advent of penicillinase-resistant penicillins limited the use of erythromycin for serious staphylococcal infections; however, erythromycin remains among the drugs of choice for the treatment of acne, infections of the skin and soft tissues, streptococcal pharyngitis, bronchitis, pneumonitis, diphtheria, carriers of pertussis, and, when administered with a sulfonamide, otitis media. Erythromycin is the drug of choice for the empiric treatment of outpatients with pneumonitis. Erythromycin is also the drug of choice for the treatment of Legionella pneumonia and is effective therapy for Chlamydia infections. Other uses of erythromycin include prophylaxis for elective colon operations and treatment of Campylobacter enteritis, genitourinary infections, and some sexually transmitted diseases.

Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin, and Metronidazole

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and also can be used for gonococcal infections in patients unable to tolerate penicillin. These drugs may cause gastrointestinal irritation, diarrhea, phototoxic dermatitis, and vestibular damage, and fatal reactions due to hepatotoxicity have occurred in pregnant women. Chloramphenicol has a broad spectrum of bacteriostatic activity, but its association with suppression of the bone marrow and aplastic anemia has relegated it to a historical role. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious adverse effects associated with the use of erythromycin is low; dose-related epigastric distress may occur. Clindamycin is bactericidal to most nonenterococcal gram-positive aerobic bacteria and many anaerobic microorganisms. Although historically it was a frequent cause of antibiotic-associated diarrhea and colitis, clindamycin is considered an excellent alternative to beta-lactam antibiotics for treatment of many staphylococcal infections, and it has therapeutic utility in anaerobic infections and in several protozoan infections in immunosuppressed patients. Metronidazole is efficacious for treating nonpulmonary anaerobic infections, various parasitic infections (trichomoniasis, amebiasis, and giardiasis), nonspecific vaginitis, and Clostridium difficile-mediated colitis. With use of metronidazole, mild side effects such as epigastric discomfort, diarrhea, reversible neutropenia, and allergic-type cutaneous reactions may occur.

Pulmonary Disease in the Immunocompromised Host (Second of Two Parts)

In this second segment of our article on pulmonary disease in the immunocompromised host (ICH), we review the infections associated with pulmonary infiltrates in the ICH and the diagnostic approaches for both infectious and noninfectious conditions. Although certain immunologic defects may predispose patients to specific infectious agents, virtually any infectious agent can cause pulmonary disease in any ICH. Physical findings and laboratory observations may give the clinician clues about probable causes of infection. Nevertheless, invasive diagnostic procedures—in particular, open-lung biopsy—are often necessary to diagnose pulmonary disease in the ICH. The relatively new technique of bronchoalveolar lavage is useful in diagnosing pulmonary disease in the patients with acquired immunodeficiency syndrome (AIDS). Further studies are necessary to confirm the reliability of this procedure as a diagnostic method in the ICH who does not have AIDS.

Tetracyclines, Chloramphenicol, Erythromycin, and Clindamycin

Tetracyclines are active in vitro against most urinary tract pathogens, Chlamydia, Mycoplasma pneumoniae, Brucella, rickettsiae, and Nocardia. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and infections due to Salmonella typhi. Erythromycin is active in vitro against M. pneumoniae, Streptococcus pneumoniae, and group A beta-hemolytic streptococci. Erythromycin may be used as prophylactic therapy for subacute bacterial endocarditis and for recurrence of acute rheumatic fever in patients who are allergic to penicillin. Clindamycin should be used only for the treatment of anaerobic infections. Tetracycline may cause gastrointestinal upset; phototoxic dermatitis; hepatitis, especially in pregnant females; discoloration of teeth and bone dysplasia in the human fetus and children; and suprainfections, especially oral and anogenital candidiasis. Tetracycline should be used with caution in patients with renal insufficiency. The most important toxic effect of chloramphenicol is bone marrow suppression, which is dose related and idiosyncratic. The incidence of undesirable side effects associated with the use of erythromycin is low. Gastrointestinal irritation is the most common; cholestatic hepatitis may occur with erythromycin estolate. Pseudomembranous colitis is the most important toxic effect associated with clindamycin.

Ciprofloxacin Versus Trimethoprim-Sulfamethoxazole: Treatment of Community-Acquired Urinary Tract Infections in a Prospective, Controlled, Double-Blind Comparison

In this study, we determined the safety and efficacy of the treatment of adults with urinary tract infection with ciprofloxacin hydrochloride (250 mg twice daily for 10 days) in comparison with trimethoprim-sulfamethoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily for 10 days). Patients with signs and symptoms of urinary tract infection were randomized to receive ciprofloxacin (98 women and 5 men) or trimethoprim-sulfamethoxazole (92 women and 8 men). The success rate of therapy was 91% for both treatment arms of the study. Among seven failures after ciprofloxacin therapy, three were due to relapse of infection and two to side effects that necessitated a change in medication; in addition, two patients had persistent symptoms and required hospitalization. Among the six failures associated with trimethoprim-sulfamethoxazole therapy, four were due to relapse, one to persistence of infection, and one to a side effect that necessitated a change in medication. Among the patients treated with trimethoprim-sulfamethoxazole, 32% had mild or moderate adverse reactions; in comparison, 17% of the ciprofloxacin-treated patients had adverse reactions (P = 0.026). For the treatment of urinary tract infection in adult patients in this study, ciprofloxacin and trimethoprim-sulfamethoxazole were equally effective, but ciprofloxacin was associated with fewer adverse reactions.