Diagnosis and management of pulmonary infection due to Rhodococcus equi.

BACKGROUND: Rhodococcus equi is a recognized cause of disease in humans, especially in individuals who are immunocompromised. Because diphtheroids are regarded as part of normal respiratory flora, the importance of R. equi as a pulmonary pathogen may not be fully appreciated and its prevalence may be underestimated. Most treatment recommendations for R. equi infection were established before antiretroviral drugs became available for human immunodeficiency virus/AIDS therapy, and therapeutic strategies may need to be updated. OBJECTIVES: To review the role of R. equi as a cause of pulmonary infection; to highlight its importance for clinicians and microbiologists; and to challenge current approaches to treatment, whether in immunodeficient or immunocompetent individuals. SOURCES: A PubMed search using combinations of the following terms: 'Rhodococcus (automatically including Corynebacterium) equi' AND 'pneumonia' OR 'pulmonary' infection, then cross-checking references in the resulting cases, case series and reviews. CONTENT: We provide a review that details the challenges in the diagnosis, microbiology and pathogenesis of pulmonary infection caused by R. equi and the options for treatment. IMPLICATIONS: Ten to 14 days of treatment may be effective for pneumonia due to R. equi. Our review suggests that longer courses of therapy are needed for cavitary lesions and lung masses. However, recommendations for excessively prolonged treatment of all pulmonary infections arose during a time when many cases occurred in individuals with AIDS and before effective antiretroviral therapy was available. We suggest that the rationale for prolonged therapy with multiple antibiotics needs to be re-evaluated.

Does active hepatitis C virus infection increase the risk for infection due to Staphylococcus aureus?

Infections with Staphylococcus aureus may be more frequent in subjects with active hepatitis C virus (HCV) infection. In this retrospective dual-cohort study, we sought to determine whether persons with active HCV infection (positive HCV antibody, detectable blood HCV RNA) were at greater risk of S. aureus infection than those with spontaneously resolved HCV infection (positive HCV antibody, negative blood HCV RNA). Based on prestudy power calculation, we included 231 subjects with active HCV and 116 subjects with resolved HCV infection. The two groups were well matched at baseline, except that subjects with active HCV had a higher mean Charlson's comorbidity index (2.2 vs. 1.3; p < 0.0001). Cohorts were followed for a mean of 3.67 years. Thirty-one of the 231 (13%) subjects with active HCV infection developed ≥1 S. aureus infection(s) as compared to 4/116 (3.4%) subjects with resolved HCV (p = 0.004), with a trend towards more recurrent S. aureus infections in subjects with active HCV infection. The S. aureus infections were mostly serious, necessitating hospitalization and intravenous antibiotics. In the logistic regression, factors that independently predicted S. aureus infection were active HCV and Charlson's comorbidity index. Our regression models confirmed that the enhanced susceptibility to S. aureus infections was related to active HCV infection and not attributable solely to the increased number of comorbidities [adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI) 1.1-9.8; p = 0.03]. This study shows that subjects with active HCV infection have a significantly higher incidence of serious S. aureus infections than those with spontaneously resolved HCV, even after adjustment for comorbidities.

Clinical prediction rules in community-acquired pneumonia: lies, damn lies and statistics.

A variety of prediction scores have been developed to identify at the time of presentation patients with community-acquired pneumonia at risk for intensive care unit (ICU) admission or death within 30 days. The effectiveness of each scoring score is typically assessed by calculation of the area under the receiver-operator characteristic curve (AUROC). Although this statistical parameter is helpful in determining the discriminatory value of a score, it assumes equal importance of false negatives and false positives in the tradeoff between sensitivity and specificity. Because patient safety takes precedence over cost, the balance between limiting false negatives (unnecessarily strict ICU admission policy) and false positives (unnecessarily liberal ICU admission policy) should favor the reduction of false negatives. Instead of using AUROC as the primary measure to evaluate prediction rules, we propose the use of sensitivity as a more appropriate alternative.

Spinal and paraspinal pneumococcal infections-a review.

Spinal and paraspinal infections caused by Streptococcus pneumoniae remain a rare event. We present two cases from our institution, discuss the pathophysiology, and present a literature review of an additional 50 cases of spinal pneumococcal infections. Spinal epidural abscess and vertebral osteomyelitis as well as paraspinal abscesses caused by pneumococcus were included in the analysis. As has been reported for spinal infections due to other bacteria, persistent localized back pain with an elevation in inflammatory markers was almost universal. The lumbar spine was the most commonly involved. Pneumococcus was most frequently isolated from material obtained at the site of the infection; blood cultures were a less common source. The majority of patients with neurologic deficits had spinal epidural abscess or phlegmon, and had a higher mortality. Most patients were treated with 6 weeks of parenteral antimicrobials, and surgical intervention was not associated with a mortality benefit.

Cerebral Scedosporium apiospermum infection presenting with intestinal manifestations.

We present a case of cerebral Scedosporium apiospermum infection presenting with intestinal manifestations in a 64-year-old male patient on immunosuppression for orthotopic liver transplantation. At admission, the patient's chief complaint was chronic watery diarrhea and he was found to have colonic ulcers on endoscopy. His hospital course was complicated by a tonic-clonic seizure caused by a left frontal brain abscess, with the causative agent being identified by culture. He was treated with lobectomy, high-dose intravenous voriconazole, and liposomal amphotericin with clinical, endoscopic, and histologic improvement. To our knowledge, S. apiospermum has not been previously described as a cause of colitis. The septate branching appearance of the Scedosporium species is similar to the more common Aspergillus species. This case of gastrointestinal Scedosporium brings into question previously reported cases of isolated gastrointestinal aspergillosis diagnosed by histopathology. Clinical suspicion for S. apiospermum must be maintained in immunosuppressed patients presenting with neurologic and gastrointestinal symptoms.

Impact of an antibiotic restriction program on antibiotic utilization in the treatment of community-acquired pneumonia in a Veterans Affairs Medical Center.

PURPOSE: The impact of an antibiotic restriction program (ARP) on the patterns of antibiotic use in the treatment of community-acquired pneumonia (CAP) was examined. We also evaluated the association between the ARP and the length of hospital stay in regard to CAP treatment and cost savings associated with the implementation of the ARP. METHODS: A retrospective cohort study of patients admitted with CAP was conducted during two 6-month periods, one prior to the ARP and one after the ARP. The health system's computerized patient record system (CPRS) was used to obtain demographics, length of hospital stays, readmission rates, blood culture results, co-morbidities, antibiotic use, and durations of therapy. A total of 130 patients met the inclusion criteria for the final analyses. Average drug costs, employee salaries, and the cost of laboratory procedures were used to assess cost savings associated with the ARP. RESULTS: From a total of 132 antibiotics that were ordered to treat CAP in the pre-ARP period, 28 were restricted (21.2%). However, the number of restricted antibiotics ordered was significantly reduced to 12 out of 114 (10.2%) antibiotics ordered in the post-ARP period (P = 0.024). In post-ARP implementation, the mean length of hospital stay was also significantly reduced from 7.6 to 5.8 days (P = 0.017), and although not statistically significant, the 30-day readmission rates declined from 16.9 to 6.2% (P = 0.097). The ARP was also associated with a saving of $943 per patient treated for CAP. CONCLUSIONS: In addition to a decrease in the antibiotic utilization and the mean length of hospital stay, the ARP may have yielded cost savings and reduced the readmission rates for those patients admitted and treated for CAP.

Fluid-containing emphysematous bullae: a spectrum of illness.

Fluid-containing emphysematous bullae are an under-reported complication of chronic obstructive pulmonary disease. The roles of bronchoscopy in the work-up and of antibiotics in the treatment are undefined. This study reports the combined results from the analysis of 16 cases treated at the present authors' institution and 36 previously reported cases. The median age at presentation was 58 yrs and the median duration of follow-up was 60 weeks. A third of the patients were asymptomatic, while two-thirds presented with symptoms, including 10% who had evidence of a severe lung infection. Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Bacteroides melaninogenicus were cultured from the bullae fluid in three symptomatic patients. Sputum and blood cultures were uninformative. Bronchoscopy, performed in two-thirds of the cases, added no diagnostic information. Antibiotic treatment did not result in a more rapid resolution of the air fluid level. Percutaneous drainage was safe and effective in four patients. In conclusion, patients with fluid-containing bullae present with a spectrum of illness. Antibiotic treatment does not hasten radiographic resolution and bronchoscopy has no diagnostic or therapeutic role.

Analysis of mutations in the pbp genes of penicillin-non-susceptible pneumococci from Turkey.

Sequence analysis of the pbp genes from 20 Streptococcus pneumoniae isolates from Turkey (eight with high-level penicillin-resistance, nine with low-level penicillin-resistance, and three that were penicillin-susceptible) was performed and phylogenetic trees were constructed. Most isolates clustered together within a single branch that was distinct from sequences deposited previously in GenBank, which suggests that these isolates have probably evolved following new recombination events. The most prominent active-site mutations, which have also been associated previously with resistance, were T371A in PBP1a, E481G followed by T451A in PBP2b, and T338A in PBP2x. All isolates also possessed a (570)SVES/TK(574) block in the PBP2b sequence, instead of the QLQPT sequence of R6, which is fairly uncommon in GenBank sequences. This is the first study to analyse alterations in the pbp sequences of pneumococci isolated in Turkey.

Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin.

The objective of this prospective pilot study was to evaluate the response of HIV-infected patients with asymptomatic syphilis to one of two intensive antibiotic treatment regimens. Thirty-one HIV-infected patients with serum rapid plasma reagin titre > or =1:4 and no clinical findings of syphilis were randomized to receive daily intramuscular injections of ceftriaxone or procaine penicillin (plus oral probenecid) for 15 days; 24 returned for follow-up study. Seven of 10 (70%) procaine penicillin-treated patients and 10 of 14 (71%) ceftriaxone-treated patients had a > or =4-fold decline in RPR (P=0.94); two penicillin-treated and one ceftriaxone-treated patient relapsed. Two patients failed ceftriaxone therapy. Three penicillin-treated, and two ceftriaxone-treated patients were serofast. Serological responses were similar in those patients with and without asymptomatic neurosyphilis. There was no difference in the serologic response to daily treatment with ceftriaxone vs that with procaine penicillin plus probenecid; both treatments were associated with comparatively high rates of serological non-response and relapse.

Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users.

The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23 F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples. Vaccinations were well-tolerated. The rate of responders was higher (P<0.05) in HIV-1 negative than in HIV-1 infected individuals. No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts. Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P<0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals. Those with CD4+ >500 cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels. Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor.

A fresh look at the definition of susceptibility of Streptococcus pneumoniae to beta-lactam antibiotics.

Definitions for susceptibility or resistance of Streptococcus pneumoniae to penicillin were not developed until penicillin-resistant pneumococci appeared in South Africa in the late 1970s. The definition that was accepted (which still remains in use) and later definitions of resistance to most other beta-lactam antibiotics were derived from laboratory and clinical data relating to the treatment of meningitis, not otitis media, sinusitis, or pneumonia. An understanding of the origin of these definitions helps to resolve the apparent paradox that infections of the respiratory tract due to seemingly beta-lactam-resistant pneumococci may still respond well to standard doses of these drugs. A recently sanctioned change in the definition of susceptibility to amoxicillin is helpful in eliminating the paradox for this drug, but it may create further confusion by implying that, on a microgram basis, amoxicillin is substantially more effective than penicillin or third-generation cephalosporins. This article examines definitions of susceptibility and resistance of pneumococci, highlighting areas that have led to confusion and proposing a new way of understanding them.

Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus ("Streptococcus milleri group") are of different clinical importance and are not equally associated with abscess.

Difficulties in distinguishing organisms of the "Streptococcus milleri group" (SMG; Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus), have caused ambiguity in determining their pathogenic potential. We reviewed 118 cases in which SMG isolates had been identified using 16S rDNA sequence. S. constellatus and S. anginosus were isolated far more frequently than was S. intermedius. Nearly all isolates of S. intermedius and most isolates of S. constellatus, but only 19% of those of S. anginosus, were associated with abscess. Our findings suggest that speciation of the SMG may guide diagnostic evaluation, give insight into the possible role of coinfecting organisms, and help assess the need to search for occult abscess.

Antibiotic susceptibilities of genetically characterized Streptococcus milleri group strains.

Previous studies of the antibiotic susceptibility of Streptococcus milleri group organisms have distinguished among species by using phenotypic techniques. Using 44 isolates that were speciated by 16S rRNA gene sequencing, we studied the MICs and minimum bactericidal concentrations of penicillin, ampicillin, ceftriaxone, and clindamycin for Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus. None of the organisms was resistant to beta-lactam antibiotics, although a few isolates were intermediately resistant; one strain of S. anginosus was tolerant to ampicillin, and another was tolerant to ceftriaxone. Six isolates were resistant to clindamycin, with representation from each of the three species. Relatively small differences in antibiotic susceptibilities among species of the S. milleri group show that speciation is unlikely to be important in selecting an antibiotic to treat infection caused by one of these isolates.

Immunogenicity of pneumococcal vaccine in heart transplant recipients.

To assess the immunogenicity of pneumococcal vaccine in recipients of heart transplants, we immunized 35 long-term transplantation survivors with pneumococcal vaccine and measured the pre- and postvaccination IgG antibody titers to 5 representative vaccine capsular polysaccharides. Responses of heart transplant recipients to pneumococcal vaccine antigens were generally suppressed.