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CASE A 79-year-old man developed Mycobacterium abscessus prosthetic joint infection (PJI) after hip hemiarthroplasty that was complicated by polymicrobial infection. He was ultimately treated with resection arthroplasty and chronic suppressive therapy. He has had no evidence of recurrent infection after 2 years of follow-up. CONCLUSION As far as we know, this is the first reported case of M. abscessus hip PJI complicated by superimposed polymicrobial infection. This case demonstrates the challenge of treating M. abscessus infection, the need for a multidisciplinary approach with aggressive surgical intervention, and prolonged combination antimicrobial therapy for a successful outcome.

This chapter highlights lung abscess, which is a chronic or subacute lung infection initiated by the aspiration of contaminated oropharyngeal secretions. The result is an indolent, necrotizing infection in a segmental distribution, usually dependent, limited by the pleura. Lung abscess is almost always associated with anaerobic bacteria, although the majority of infections are polymicrobial with microaerophilic and aerobic bacteria present. In contrast, necrotizing pneumonia is an acute, often fulminant, infection characterized by irregular destruction of alveolar walls and therefore multiple cavities. This infection spreads rapidly through lung tissue, frequently crossing interlobar fissures, and is often associated with pleural effusion and empyema. The duration of illness before recognition is usually only a few days. The chapter then looks at the diagnosis and therapy of anaerobic lung abscess.

Context: Delayed, postoperative, spine infections are rare, most commonly occurring secondary to fastidious, less virulent pathogens. The etiology may involve a distant infectious focus, not related to the index operation. Patients may present months, or even years postoperatively with pain related to mechanical implant failure, often without additional signs of systemic infection. Findings: We present the case of a 59-year-old male who developed rapid disk degeneration and implant failure seven months following instrumented lumbar fusion surgery. The causal organism was found to be Micromonas micros, an anaerobic bacterium typically located in the oral cavity and associated with periodontal disease. The patient was found to have extensive oral caries, which were presumed to have occurred secondary to poor oral hygiene and his use of fentanyl lozenges for chronic back pain. The patient was treated with revision staged spinal surgery and long-term intravenous antibiotics. Conclusion/clinical relevance: This case highlights an unusual etiology of delayed postoperative spinal implant failure and provides evidence for periodontal disease as a source of hematogenous seeding in postoperative spinal infections. The orthopaedist should also be aware of the potential relationship between poor oral hygiene and the use of high sugar content fentanyl lozenges in treating chronic back pain in these patients.

Background The utility of convalescent coronavirus disease 2019 (COVID-19) plasma (CCP) in the current pandemic is not well defined. We sought to evaluate the safety and efficacy of CCP in severely or life threateningly ill COVID-19 patients when matched with a contemporaneous cohort. Methods Patients with severe or life-threatening COVID-19 were treated with CCP according to Food and Drug Administration criteria, prioritization by an interdisciplinary team, and based on CCP availability. Individual-level matched controls (1:1) were identified from patients admitted during the prior month when no CCP was available. The safety outcome was freedom from adverse transfusion reaction, and the efficacy outcome was a composite of death or worsening O2 support. Demographic, clinical, and laboratory data were analyzed by univariate and multivariable regression analyses accounting for matched design. Results Study patients (n = 94, 47 matched pairs) were 62% male with a mean age of 58, and 98% (90/94) were minorities (53% Hispanic, 45% Black, non-Hispanic) in our inner-city population. Seven-day composite and mortality outcomes suggested a nonsignificant benefit in CCP-treated patients (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.23–2.12; P = .52; aHR, 0.23; 95% CI, 0.04–1.51; P = .13, respectively). Stratification by pretransfusion mechanical ventilation status showed no differences between groups. No serious transfusion reactions occurred. Conclusions In this short-term matched cohort study, transfusion with CCP was safe and showed a nonsignificant association with study outcomes. Randomized and larger trials to identify appropriate timing and dosing of CCP in COVID-19 are warranted. Trial Registration ClinicalTrials.gov Identifier: NCT04420988.

Brevibacteria are Gram-positive rods found in human skin flora and dairy products. Although generally not considered human pathogens, case reports have implicated Brevibacterium species as rare causes of bacteremia, endocarditis, peritonitis, and osteomyelitis. We report a case of Brevibacterium tibial osteomyelitis in an immunocompetent individual with implanted hardware and highlight the challenge of identifying the organism and recognizing it as a potential pathogen.

Ludwig’s angina is a rapidly spreading infection of the floor of the mouth and neck. A rare and dreaded complication of Ludwig’s angina is extension of the infection to the mediastinum. We describe a unique case of Ludwig’s angina presenting with descending necrotizing mediastinitis, with the subsequent development of Candida albicans and Candida krusei mediastinitis.

Mucocutaneous leishmaniasis (MCL) is a rare infection caused by several species within the genus Leishmania. We present a patient with multifocal MCL masquerading as idiopathic midline granulomatous disease, featuring the unusual complication of ocular leishmaniasis, as a result of prolonged immunosuppressive therapy. We review clinical features, diagnosis, and treatment of this syndrome.

Clostridium subterminale is a low virulence species of Clostridium that is an infrequent cause of human infections. We report a case of C. subterminale bacteremia in an immunocompetent patient who developed botulism-like symptoms.

Histoplasma capsulatum, a dimorphic fungus found world-wide, is endemic to regions of the Mississippi and Ohio River valleys and portions of Central and South America. Initial infection can present with acute pulmonary symptoms or remain clinically asymptomatic, with disease course generally guided by degree of inoculum and underlying immunosuppression. A chronic, progressive course of weight loss, oral ulceration, and fatigue has been associated with elderly males. We present a 79-year-old man with a chronic, progressive course of oral lesions, odynophagia, and weight loss who was found to have histoplasmosis on oral biopsy performed for suspicions of oropharyngeal squamous cell carcinoma. Histoplasma urine antigen, serum complement fixation antibody titers, and fungal tissues were all negative despite validated sensitivities in the >90% range. Our case report highlights the critical role of tissue biopsy in establishing a diagnosis of oropharyngeal histoplasmosis.

Historically regarded as a skin commensal, Staphylococcus epidermidis has been increasingly implicated in invasive foreign body infections such as catheter-related bloodstream infections, indwelling device infections, and prosthetic joint infections. We report a case of an aggressive, difficult-to-eradicate, invasive prosthetic hip infection occurring early after hardware implant and associated with a high-grade bacteremia and assess its salient molecular characteristics. The clinical and molecular characteristics of this isolate mirror the pathogenesis and persistence commonly seen with invasive methicillin-resistant S. aureus and may be attributed to the combination of resistance genes (SCCmec type IV), putative virulence factors (arcA and opp3a), cytolytic peptide production (α-type phenol-soluble modulins), and biofilm adhesion, interaction, and maturation (bhp, aap, and β-type phenol-soluble modulins).

Daptomycin has demonstrated clinical efficacy in the treatment of methicillin-resistant Staphylococcus aureus-associated bacteremia and right-sided infective endocarditis. Although daptomycin is not approved for treatment of gram-positive pneumonia, clinical evidence suggests that it may be effective therapy for S. aureus-associated septic pulmonary emboli (SPE). We present our clinical experience with the use of daptomycin in combination with rifampin in four patients with SPE in the absence of infective endocarditis. Three of the patients had a history of injection drug use; two of these patients also had soft-tissue infections. All patients had clinical resolution of their infections. Daptomycin and rifampin appear to have a role in the treatment of methicillin-resistant S. aureus bacteremia with SPE in the absence of infective endocarditis and should be considered in patients that have failed therapy with vancomycin.

Purpose Several recent studies showed an increase in methicillin-resistant Staphylococcus aureus (MRSA) hand infections. The purpose of this study was to determine the prevalence of community-acquired MRSA hand infections in an urban setting and to determine independent risk factors for such infections. Methods A retrospective chart review of patients with hand infections was performed from 2002 to 2009. Those with community-acquired hand infections who had surgical irrigation and debridement and intraoperative culture were entered into the study. Patient demographics—including age and gender; mechanism of injury; infection risk factors (diabetes, chronic hepatitis, intravenous intravenousdrug use, and immune-compromised conditions); place of residence/housing status; history of hospitalization, prior antibiotics use and surgery; and culture results, erythrocyte sedimentation rate, C-reactive protein, and white blood cell count—were extracted from the medical records. Regression analyses were performed to identify significant risk factors for MRSA infection. Results A total of 102 patients met our inclusion criteria. The MRSA organism was identified in 32 patients. In the analysis of all the potential risk factors, only intravenous drug use showed significant correlation with MRSA infection. Conclusions In our patients, only intravenous drug use correlated with community-acquired MRSA hand infections. Patient education about intravenous drug use and empiric treatment with MRSA-appropriate antibiotics for intravenous drug users presenting with hand infections are recommended. Type of study/level of evidence Prognostic IV.

Digital clubbing is characterized by bulbous enlargement of the distal phalanges due to an increase in soft tissue. It has been associated with a variety of conditions including cyanotic heart disease, neoplasms and infections of the lungs, bronchiectasis, liver cirrhosis, and inflammatory bowel disease. We conducted an observational study at an urban Veterans Affairs Medical Center outpatient HIV clinic to confirm our clinical impression that clubbing is common in HIV-infected patients and to identify factors that might be associated with it. Clinical, laboratory, and physical examination data including measurement of the circumference of the nail bed and distal phalanx of each finger were obtained on 78 HIV-infected patients seen for their routine care over a 3-month period. A digital index (DI), the ratio of the nail bed:distal phalanx circumference was determined for each patient. Clubbing was found in 28 patients (36%). Clubbed patients did not differ from nonclubbed patients with respect to most patient characteristics; CD4 cell counts and quantitative HIV RNA were similar in both groups. Clubbed patients had a significantly higher DI than controls (1.03 versus 0.96, p < 0.001), were younger (45 versus 49 years, p = 0.04), and had longer duration of HIV disease (48 versus, 42 months, p = 0.03). HIV infection should be considered in the differential diagnosis of acquired digital clubbing.

Although highly active antiretroviral therapy has improved the clinical course of patients with HIV, this population remains at a significantly increased risk for non-Hodgkin's lymphoma (NHL). Spinal cord compression is a rare presentation of NHL, regardless of the patient population. We encountered a patient with HIV-related NHL who presented with a thoracic spinal cord compression and had a complicated clinical course as a result of the atypical presentation.

The benefit of antimicrobial therapy for patients with an acute exacerbation of chronic bronchitis (AECB) remains controversial for two main reasons. First, the distal airways of patients with chronic bronchitis are persistently colonised, even during clinically stable periods, with the same bacteria that have been associated with AECB. Second, bacterial infection is only one of several causes of AECB. These factors have led to conflicting analyses on the role of bacterial agents and the response to antimicrobial therapy of patients with AECB. An episode of AECB is said to be present when a patient with chronic obstructive pulmonary disease (COPD) experiences some combination of increased dyspnoea, increased sputum volume, increased sputum purulence and worsening lung function. While the average COPD patient experiences 2 - 4 episodes of AECB per year, some patients, particularly those with more severe airway obstruction, are more susceptible to these attacks than others. Bacterial agents appear to be particularly associated with AECB in patients with low lung function and those with frequent episodes accompanied by purulent sputum. Non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis account for up to 50% of episodes of AECB. Gram-negative bacilli are more likely to occur in patients with more severe lung disease. Antibiotics have been used to ameliorate AECB, to prevent AECB and to prevent the long-term loss of lung function that characterises COPD. Numerous prevention trials have been conducted with fairly consistent results; antibiotics do not lessen the number of episodes of AECB but do reduce the number of days lost from work. Most antibiotic trials have studied the impact of treatment on episodes of AECB and results have been inconsistent, largely due to patient selection and end point definition. In patients with severe airway obstruction, especially in the presence of purulent sputum, antibiotic therapy significantly shortens the duration of symptoms and can be cost-effective. Over the past 50 years, virtually all classes of antimicrobial agents have been studied in AECB. Important considerations include penetration into respiratory secretions, spectrum of activity and antimicrobial resistance. These factors limit the usefulness of drugs such as amoxicillin, erythromycin and trimethoprim-sulfamethoxazole. Extended-spectrum oral cephalosporins, newer macrolides and doxycycline have demonstrated efficacy in clinical trials. Amoxicillin-clavulanate and flouoroquinolones should generally be reserved for patients with more severe disease. A number of investigational agents, including ketolides and newer quinolones, hold promise for treatment of AECB.

Many veterans who were deployed to the Persian Gulf during the 1990-1991 Gulf War developed multiple unexplained symptoms such as pain, fatigue, and neurocognitive problems. This constellation of symptoms has been termed Gulf War Veterans' Illnesses (GWVI). Although there is no proven explanation for the cause of GWVI, one fairly widespread explanation is systemic Mycoplasma fermentans infection. The Antibiotic Treatment Trial of GWVI is a randomized placebo-controlled trial to determine whether a 1-year course of doxycycline treatment in deployed Gulf War veterans with GWVI and testing as Mycoplasma species positive will improve their overall functional status as measured by the Physical Component Summary of the SF-36V questionnaire. The study of a multisymptom illness such as GWVI is complicated by the nonspecific nature of the illness, the unknown etiology, and the lack of a widely accepted outcome measure. The presumption of mycoplasma infection raises concerns regarding the methodology for determination of mycoplasma infection, the choice of treatment, and the duration of treatment. However, such a presumption allows the formulation of a clear testable hypothesis that can be tested with treatments with known rates of adverse events and known activity against Mycoplasma species. This paper describes the major issues faced by the investigators during planning, the study design, the patient screening results, and the baseline characteristics of the study patients. There were 2712 patients screened for study entry at 26 Department of Veterans Affairs and two Department of Defense medical centers. Of these, 491 met all study entry criteria and were randomized to either 1 year of doxycycline (200 mg/day) or 1 year of placebo. All patients were seen monthly during treatment and at 6 months after the end of treatment. Study patients had a mean age of 41 years and were mostly male (86%), white (64%), married (68%), and employed full-time (71%).

Bacterial infection is the most common cause of excess morbidity and mortality in patients who require endotracheal intubation or tracheostomy. The normal lung is sterile distal to the central carina, despite the daily inoculation of bacteria. Aspiration of liquids is prevented by reflex closure of the glottis following stimulation of receptors in the larynx and trachea and by the vigorous coughing that such stimulation evokes. Impairment of mucociliary function and mucus hypersecretion leads to pooling of secretions in the airways of intubated patients. Bacteria presented to the lung in a liquid bolus, such as contaminated upper-airway secretions, are cleared more slowly than bacteria presented as aerosols. Colonization by gram-negative bacilli (GNB) and other cextends to multiple contiguous sites including the oropharynx, endotracheal tube, tracheobronchial secretions, and stomach. Tracheobronchitis can be diagnosed when secretions become purulent, usually associated with an increased volume, viscosity, or both, with no new infiltrates visible on the chest radiograph. Tracheobronchitis frequently precedes nosocomial pneumonia in patients with endotracheal tubes or tracheostomies. Respiratory infection in patients with artificial airways is a dynamic process with virtually continuous inoculation of the airways with a changing bacterial flora, most of which is contained by lung defenses but with varying degrees of resultant inflammation. Sinusitis is clearly associated with an increased risk of nosocomial pneumonia, presumably due to the likelihood of aspiration of grossly infected material into the distal airways.

A case-control study of patients with stools assayed forClostridium difficiletoxin over a 24-month period at a Veterans Affairs hospital found that the majority of cases (70.6%) occurred in temporal clusters. Clustering was particularly evident on a designated human immunodeficiency virus (RW) unit. Thirty-four (75.5%) of 45 HIV-infected patients withC difficile-associated diarrhea (CDAD) died during their hospitalization. Third-generation cephalosporins were the antibiotics most strongly associated with CDAD.

We reviewed the effect of adding maraviroc on CD4 cell counts in nine patients on antiretroviral therapy with full viral suppression but impaired CD4 cell recovery. There were no significant differences in changes in CD4 cell count, percentage of CD4 cells, or in the ratio of CD4/CD8 cells at 30 days and 25 weeks of maraviroc therapy. Plasma endotoxin levels measured in four patients before and during maraviroc treatment also showed no significant differences.

In a cohort of 23 critically ill patients receiving continuous renal replacement therapy, we investigated the role of ultrafiltrate fluid cultures as an adjunct to blood cultures in identifying the microbial etiology of sepsis. We found they provided no additional benefit and may yield false positives due to contamination.

Borrelia burgdorferi, the agent of Lyme disease, and B. turicatae, a neurotropic agent of relapsing fever, are susceptible to vancomycin in vitro, with an MIC of 0.5 microgram/ml. To determine the activity of vancomycin in vivo, particularly in the brain, we infected adult immunocompetent BALB/c and immunodeficient CB-17 scid mice with B. burgdorferi or B. turicatae. The mice were then treated with vancomycin, ceftriaxone as a positive control, or normal saline as a negative control. The effectiveness of treatment was assessed by cultures of blood and brain and other tissues. Ceftriaxone at a dose of 25 mg/kg of body weight administered every 12 h for 7 to 10 days eliminated cultivable B. burgdorferi or B. turicatae from all BALB/c or scid mice in the study. Vancomycin at 30 mg/kg administered every 12 h was effective in eliminating infection from immunodeficient mice if treatment was started within 3 days of the onset of infection. If treatment with vancomycin was delayed for 7 days or more, vancomycin failed to eradicate infection with B. burgdorferi or B. turicatae from immunodeficient mice. The failure of vancomycin in eradicating established infections in immunodeficient mice was associated with the persistence of viable spirochetes in the brain during antibiotic treatment.

Aspiration bronchopneumonia occurs in most patients undergoing prolonged mechanical ventilation. These pneumonias adversely affect lung function and release bacteria into the systemic circulation via the lungs' lymphatics. Through this mechanism, clinically occult pneumonias may initiate activation of systemic inflammation, leading to the syndrome of multiple organ failure.

We describe three patients with AIDS who developed clinically significant infection with Mycobacterium haemophilum. One patient had skin and bone involvement and suspected laryngeal involvement; the second had extensive abdominal adenopathy with partial bowel obstruction; and the third presented with limited skin involvement. Each patient responded transiently to antimycobacterial therapy, but disease recurred and progressed in all three cases. Recovery of M. haemophilum requires a high level of clinical suspicion and special handling of mycobacterial cultures by the microbiology laboratory, including cultivation on enriched chocolate agar or heme-supplemented media and incubation at 30 degrees C for up to 8 weeks. Characteristic patterns of drug susceptibility for this organism have been only partially defined. Reported responses to antimycobacterial therapy in AIDS patients with M. haemophilum infection have been poor, and the optimal therapeutic regimen is not yet known. The prognosis for recovery appears to depend heavily on host-related factors, particularly the degree of immunosuppression.

The in vitro activity of the everninomicin antibiotic SCH 27899 against 17 isolates of Borrelia spp. was investigated. MICs ranged from 0.06 to 0.5 μg/ml. Time-kill studies with the B31 strain of B. burgdorferi demonstrated ≥3-log 10 -unit killing after 72 h with concentrations representing four times the MIC. The in vitro activity of four other newer antimicrobial agents, meropenem, cefepime, quinupristin-dalfopristin, and linezolid, was also tested against the B31 strain. Meropenem was the most potent of the latter agents, with an MIC of 0.125 μg/ml.

Although highly active antiretroviral therapy has improved the clinical course of patients with HIV, this population remains at a significantly increased risk for non-Hodgkin's lymphoma (NHL). Spinal cord compression is a rare presentation of NHL, regardless of the patient population. We encountered a patient with HIV-related NHL who presented with a thoracic spinal cord compression and had a complicated clinical course as a result of the atypical presentation.

The emergence of antibiotic resistance in Streptococcus pneumoniae poses a particular threat to HIV-infected patients. These patients are at increased risk of invasive pneumococcal disease and may respond poorly to pneumococcal vaccination. We describe an HIV-infected patient with recurrent aortic valve endocarditis due to the same serotype of S. pneumoniae (19A) despite appropriate treatment with penicillin and immunoprophylaxis. The pneumococcus responsible for the second episode of endocarditis was susceptible to cefotaxime (MIC of 0.06 microg/ml), but was no longer susceptible to penicillin (MIC of 0.25 microg/ml). The patient was treated successfully with 4 weeks of intravenous ceftriaxone.

Background It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. Objective To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. Design A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. Setting 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. Participants 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. Intervention Doxycycline, 200 mg, or matching placebo daily for 12 months. Measurements The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. Results No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. Limitations Adherence to treatment after 6 months was poor. Conclusion Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.

Many veterans who were deployed to the Persian Gulf during the 1990-1991 Gulf War developed multiple unexplained symptoms such as pain, fatigue, and neurocognitive problems. This constellation of symptoms has been termed Gulf War Veterans' Illnesses (GWVI). Although there is no proven explanation for the cause of GWVI, one fairly widespread explanation is systemic Mycoplasma fermentans infection. The Antibiotic Treatment Trial of GWVI is a randomized placebo-controlled trial to determine whether a 1-year course of doxycycline treatment in deployed Gulf War veterans with GWVI and testing as Mycoplasma species positive will improve their overall functional status as measured by the Physical Component Summary of the SF-36V questionnaire. The study of a multisymptom illness such as GWVI is complicated by the nonspecific nature of the illness, the unknown etiology, and the lack of a widely accepted outcome measure. The presumption of mycoplasma infection raises concerns regarding the methodology for determination of mycoplasma infection, the choice of treatment, and the duration of treatment. However, such a presumption allows the formulation of a clear testable hypothesis that can be tested with treatments with known rates of adverse events and known activity against Mycoplasma species. This paper describes the major issues faced by the investigators during planning, the study design, the patient screening results, and the baseline characteristics of the study patients. There were 2712 patients screened for study entry at 26 Department of Veterans Affairs and two Department of Defense medical centers. Of these, 491 met all study entry criteria and were randomized to either 1 year of doxycycline (200 mg/day) or 1 year of placebo. All patients were seen monthly during treatment and at 6 months after the end of treatment. Study patients had a mean age of 41 years and were mostly male (86%), white (64%), married (68%), and employed full-time (71%).

Nosocomial pneumonia, or terminal pneumonia as it was formerly called, results from the repetitive microaspiration of contaminated oropharyngeal secretions into the lungs in the presence of impaired host defenses. This pathophysiologic sequence was suggested by the observations of Osler but clarified by the seminal work of Rouby and colleagues. The enormous impact of antimicrobial agents on the organisms responsible for nosocomial pneumonias was first identified by Kneeland and Price who found that organisms of the normal pharyngeal flora virtually disappeared in terminal pneumonias following administration of these drugs, being replaced by gram-negative bacilli. The remarkable susceptibility of seriously ill patients to becoming colonized by exogenous organisms, even in the absence of antimicrobial therapy, was shown by Johanson et al. These factors, antibiotics and the change in bacterial binding receptors in the airways associated with illness, lead to infections caused by exogenous organisms that are frequently resistant to antimicrobial agents. Clinical findings that usually identify patients with respiratory infections are unreliable for the diagnosis of nosocomial pneumonias as shown by Andrews et al. Invasive techniques, especially the protected specimen brush (PSB) technique, avoid contamination of the specimen by proximal secretions and accurately reflect the bacterial burden of the lung, as first shown by Chastre et al. Quantitation of such specimens serves as an excellent proxy for direct cultures of the lung and are the current gold standard for diagnosis.

Telithromycin is a new ketolide antimicrobial, specifically developed for the treatment of community-acquired respiratory tract infections. It has a wide spectrum of antibacterial activity against common respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes. It also has activity against atypical pathogens, such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. Telithromycin maintains activity against beta-lactam and macrolide-resistant respiratory tract pathogens and does not appear to induce cross-resistance to other members of the macrolide-lincosamide-streptogramin (MLS) group of antimicrobials. It demonstrates bactericidal activity against S. pneumoniae and H. influenzae and has a prolonged concentration-dependent post-antibiotic effect (PAE) in vitro. The drug has favourable pharmacokinetics following oral administration. It is well absorbed, achieves good plasma levels and is highly concentrated in pulmonary tissues and white blood cells. In clinical trials, telithromycin given orally at a dose of 800 mg once daily for 5 - 10 days was as effective as comparator antimicrobials for the treatment of adults with community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute maxillary sinusitis and group A-beta-haemolytic streptococcal pharyngitis or tonsillitis. The adverse events and safety profile were similar to comparator antimicrobials. The most common adverse events were diarrhoea, nausea, headache and dizziness. Telithromycin should provide an effective, convenient and well-tolerated once-daily oral therapy for treatment of respiratory infections.

BACKGROUND: Hyperglycemia and new-onset diabetes mellitus have been reported to occur in HIV-infected patients treated with protease inhibitors. OBJECTIVE: To determine the effect of protease inhibitor therapy on serum glucose in a predominantly minority patient population. DESIGN: Retrospective record review. SETTING: Clinical HIV program of an urban Veterans Affairs medical center. PATIENTS: All HIV-infected patients receiving a protease inhibitor over a one-year period from September 1996 through August 1997. RESULTS: One hundred seventeen patients not previously known to be diabetic received protease inhibitors; seven (6%) developed symptomatic diabetes mellitus. Eight other patients had one or more serum glucose values >150 mg/dL. Mean random glucose values for patients who did not develop diabetes were higher during therapy than prior to initiation of protease inhibitors. CONCLUSIONS: Urban minority HIV-infected patients receiving combination antiretroviral therapy including a protease inhibitor may be at increased risk for the development of hyperglycemia and diabetes mellitus. Risk factors for diabetes mellitus should be identified and blood glucose monitored in all patients receiving protease inhibitors.

Background: Colonization and infection with vancomycin-resistant Enterococcus faecium (VREF) has been associated with the use of vancomycin and other antibiotics in individual patients. The objective of this study was to determine the association of VREF with the aggregate usage of antibiotics on nursing units in a hospital. Methods: This was a retrospective correlation study. A usage ratio was calculated for each parenteral antibiotic on each nursing unit as the per-bed usage by weight of that antibiotic divided by its average usage throughout the hospital. An average usage ratio (AUR) for each nursing unit was calculated as the mean of usage ratios of individual antibiotics. The AUR was used to compare the usage of antibiotics among nursing units in the hospital. The incidence of VREF infections on individual nursing units in a Veterans Affairs Medical Center was correlated with the usage of parenteral antibiotics separately and in aggregate in univariate and multivariate regression analyses. Results: The AUR was strongly and positively correlated with the recovery of VREF on individual nursing units. By univariate analyses, increasing use of each antibiotic tested was associated with isolation of VREF but only clindamycin remained significant in the multivariate model. However, usage of various antibiotics was highly interrelated, and only clindamycin usage was significantly correlated with usage of all other antibiotics studied. Intensive care and acute care units and units with fewer patient beds were more likely to have patients with VREF infection than were subacute care units ( p p Conclusions: VREF infections were associated with greater aggregate antibiotic use on nursing units. Determination of antibiotic usage ratios may provide a convenient and useful tool for examining the association of antibiotic usage with other nosocomial infections. (AJIC Am J Infect Control 1998;26:40-46)

Colonization with vancomycin-resistant Enterococcus faecium (VREF) is strongly associated with previous antimicrobial therapy. The gastrointestinal (GI) tract appears to be the major reservoir for this organism. We used antibiotic-treated Swiss Webster mice to study GI tract colonization with a characterized strain of VREF (E. faecium 228). Mice were pretreated with antibiotics in their daily drinking water and inoculated with 10(9) colony-forming units (CFU) of E. faecium 228 by oral gavage. We were able to establish persistent colonization with high concentrations of E. faecium 228 (8.0 log10 CFU/g of feces) in animals treated with 5 mg/ml of streptomycin plus 1 mg/ml of cefotetan. RP 59500, a streptogramin antibiotic with good in vitro activity against VREF, was administered orally in mice (n = 8) colonized with E. faecium 228. After 14 days of treatment VREF was undetectable in feces of all treated mice (3.0 CFU/g). Seven days after discontinuation of RP 59500, VREF was present in the feces of all animals. VREF isolates recovered after treatment remained susceptible to RP 59500. Attempts to eradicate E. faecium 228 colonization by oral administration of a vancomycin-sensitive E. faecium strain (SF68) or Lactobacillus spp. were unsuccessful as long as animals continued to receive streptomycin and cefotetan. Recovery of E. faecium 228 from cultures of livers and gallbladders in some animals with persistent GI tract colonization suggests that the organisms may also colonize the hepatobiliary system.

New therapies for vancomycin-resistant Enterococcus faecium (VREF) infections are urgently needed. We describe the treatment of 15 patients with VREF infection with quinupristin/dalfopristin (RP 59500), a new injectable streptogramin antibiotic. Primary infections treated were bacteremia (4), urinary tract (4), intraabdominal (5), otitis externa (1), and meningitis (1). Minimum inhibitory concentrations for quinupristin/dalfopristin ranged from 0.5 microgram/ml or less to 2 micrograms/ml, and minimum bactericidal concentrations were greater than 64 micrograms/ml for all VREF isolates tested. Peak serum inhibitory titers following infusion of quinupristin/dalfopristin ranged from 1:8 to 1:64; all bactericidal titers were less than 1:2. Development of resistance to quinupristin/dalfopristin during therapy was not observed. The only drug-related adverse effect noted was phlebitis in 4 patients; all had received quinupristin/dalfopristin by peripheral venous infusion. Three patients had clinical and bacteriologic cures. Relapses occurred in 5 patients with recovery of VREF from infected sites in post-treatment cultures. Ten patients died of severe underlying disease; VREF was believed to contribute directly to the death of only 1 patient. While evaluation of clinical efficacy was complicated by the severity of underlying disease in patients with VREF infection, our experience suggests that quinupristin/dalfopristin is a safe and potentially useful agent for the treatment of VREF infections.