Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure.

OBJECTIVES: Telavancin is approved in Europe for the treatment of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus when other alternatives are not suitable. The approved European prescribing information contraindicates the use of telavancin in patients with severe renal impairment (creatinine clearance <30 mL/min, including patients on haemodialysis) and pre-existing acute renal failure owing to the higher observed mortality in these patients. Data from the ATTAIN studies were reanalysed, excluding patients with these contraindicating conditions at baseline. (At the time of submission of this article, the European marketing authorization of telavancin for the treatment of nosocomial pneumonia was suspended pending evidence of a new European Medicines Agency-approved supplier. Clinigen Healthcare Ltd, Theravance's commercialization partner for telavancin in Europe, is in the process of seeking approval of a new manufacturing source.) METHODS: A post hoc analysis of data from two Phase 3 ATTAIN trials of telavancin for the treatment of Gram-positive nosocomial pneumonia assessing clinical outcomes and safety. RESULTS: The all-treated population for this analysis represented 84.2% (1266/1503) of the ATTAIN all-treated population. The cure rates in the clinically evaluable population were similar in the telavancin (82.5%, 231/280) and vancomycin (81.3%, 243/299) groups [treatment difference (95% CI): 1.3% (-5.0% to 7.6%)], and were consistent with the overall ATTAIN study results. The cure rate was higher in the telavancin than the vancomycin treatment group in microbiologically evaluable patients with only Gram-positive pathogens isolated at baseline [85.0% (130/153) versus 75.2% (109/145), respectively; treatment difference (95% CI): 9.7% (0.6%-18.8%)]. The incidences of adverse events were similar between treatment groups and consistent with the overall findings of the ATTAIN study. CONCLUSIONS: This analysis demonstrated that in the subset of patients without severe renal impairment or pre-existing acute renal failure, clinical and safety outcomes were similar in the telavancin and vancomycin treatment groups.

Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery.

BACKGROUND: Despite the routine use of prophylactic systemic antibiotics, surgical-site infection continues to be associated with significant morbidity and cost after colorectal surgery. The gentamicin-collagen sponge, an implantable topical antibiotic agent, is approved for surgical implantation in 54 countries. Since 1985, more than 1 million patients have been treated with the sponges. METHODS: In a phase 3 trial, we randomly assigned 602 patients undergoing open or laparoscopically assisted colorectal surgery at 39 U.S. sites to undergo either the insertion of two gentamicin-collagen sponges above the fascia at the time of surgical closure (the sponge group) or no intervention (the control group). All patients received standard care, including prophylactic systemic antibiotics. The primary end point was surgical-site infection occurring within 60 days after surgery, as adjudicated by a clinical-events classification committee that was unaware of the study-group assignments. RESULTS: The incidence of surgical-site infection was higher in the sponge group (90 of 300 patients [30.0%]) than in the control group (63 of 302 patients [20.9%], P=0.01). Superficial surgical-site infection occurred in 20.3% of patients in the sponge group and 13.6% of patients in the control group (P=0.03), and deep surgical-site infection in 8.3% and 6.0% (P=0.26), respectively. Patients in the sponge group were more likely to visit an emergency room or surgeon's office owing to a wound-related sign or symptom (19.7%, vs. 11.0% in the control group; P=0.004) and to be rehospitalized for surgical-site infection (7.0% vs. 4.3%, P=0.15). The frequency of adverse events did not differ significantly between the two groups. CONCLUSIONS: Our large, multicenter trial shows that the gentamicin-collagen sponge is not effective at preventing surgical-site infection in patients who undergo colorectal surgery; paradoxically, it appears to result in significantly more surgical-site infections. (Funded by Innocoll Technologies; ClinicalTrials.gov number, NCT00600925.)

Phase 2, randomized, double-blind, dose-ranging study evaluating the safety, tolerability, population pharmacokinetics, and efficacy of oral torezolid phosphate in patients with complicated skin and skin structure infections.

Torezolid (TR-700) is the active moiety of the prodrug torezolid phosphate ([TP] TR-701), a second-generation oxazolidinone with 4- to 16-fold greater potency than linezolid against Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind phase 2 study evaluated three levels (200, 300, or 400 mg) of oral, once-daily TP over 5 to 7 days for complicated skin and skin structure infections (cSSSI). Patients 18 to 75 years old with cSSSI caused by suspected or confirmed Gram-positive pathogens were randomized 1:1:1. Of 188 treated patients, 76.6% had abscesses, 17.6% had extensive cellulitis, and 5.9% had wound infections. S. aureus, the most common pathogen, was isolated in 90.3% of patients (139/154) with a baseline pathogen; 80.6% were MRSA. Cure rates in clinically evaluable patients were 98.2% at 200 mg, 94.4% at 300 mg, and 94.4% at 400 mg. Cure rates were consistent across diagnoses, regardless of lesion size or the presence of systemic signs of infection. Clinical cure rates in patients with S. aureus isolated at baseline were 96.6% overall and 96.8% for MRSA. TP was safe and well tolerated at all dose levels. No patients discontinued treatment due to an adverse event. Three-stage hierarchical population pharmacokinetic modeling yielded a geometric mean clearance of 8.28 liters/h (between-patient variability, 32.3%), a volume of the central compartment of 71.4 liters (24.0%), and a volume of the peripheral compartment of 27.9 liters (35.7%). Results of this study show a high degree of efficacy at all three dose levels without significant differences in the safety profile and support the continued evaluation of TP for the treatment of cSSSI in phase 3 trials.

Effect of an implantable gentamicin-collagen sponge on sternal wound infections following cardiac surgery: a randomized trial.

CONTEXT: Despite the routine use of prophylactic systemic antibiotics, sternal wound infection still occurs in 5% or more of cardiac surgical patients and is associated with significant excess morbidity, mortality, and cost. The gentamicin-collagen sponge, a surgically implantable topical antibiotic, is currently approved in 54 countries. A large, 2-center, randomized trial in Sweden reported in 2005 that the sponge reduced surgical site infection by 50% in cardiac patients. OBJECTIVE: To test the hypothesis that the sponge prevents infection in cardiac surgical patients at increased risk for sternal wound infection. DESIGN, SETTING, AND PARTICIPANTS: Phase 3 single-blind, prospective randomized controlled trial, 1502 cardiac surgical patients at high risk for sternal wound infection (diabetes, body mass index >30, or both) were enrolled at 48 US sites between December 21, 2007, and March 11, 2009. INTERVENTION: Single-blind randomization to insertion of 2 gentamicin-collagen sponges (total gentamicin of 260 mg) between the sternal halves at surgical closure (n = 753) vs no intervention (control group: n = 749). All patients received standardized care including prophylactic systemic antibiotics and rigid sternal fixation. MAIN OUTCOME MEASURES: The primary end point was sternal wound infection occurring through 90 days postoperatively as adjudicated by a clinical events classification committee blinded to study treatment group. The primary study comparison was done in the intent-to-treat population. Secondary outcomes included (1) superficial wound infection (involving subcutaneous tissue but not extending down to sternal fixation wires), (2) deep wound infection (involving the sternal wires, sternal bone, and/or mediastinum), and (3) score for additional treatment, presence of serous discharge, erythema, purulent exudate, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay (ASEPSIS; minimum score of 0 with no theoretical maximum). RESULTS: Of 1502 patients, 1006 had diabetes (67%) and 1137 were obese (body mass index >30) (76%). In the primary analysis, there was no significant difference in sternal wound infection in 63 of 753 patients randomized to the gentamicin-collagen sponge group (8.4%) compared with 65 of 749 patients randomized to the control group (8.7%) (P = .83). No significant differences were observed between the gentamicin-collagen sponge group and the control group, respectively, in superficial sternal wound infection (49/753 [6.5%] vs 46/749 [6.1%]; P = .77), deep sternal wound infection (14/753 [1.9%] vs 19/749 [2.5%]; P = .37), ASEPSIS score (mean [SD], 1.9 [6.4] vs 2.0 [7.2]; P = .67), or rehospitalization for sternal wound infection (23/753 [3.1%] vs 24/749 [3.2%]; P = .87). CONCLUSION: Among US patients with diabetes, high body mass index, or both undergoing cardiac surgery, the use of 2 gentamicin-collagen sponges compared with no intervention did not reduce the 90-day sternal wound infection rate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00600483.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Clinical characteristics and outcomes of diabetic patients with Staphylococcus aureus bacteremia and endocarditis.

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators.

BACKGROUND: Although cardiac device infections (CDIs) are a devastating complication of permanent pacemakers or implantable cardioverter-defibrillators, the incidence of CDI in patients with bacteremia is not well defined. The objective of this study was to determine the incidence of CDI among patients with permanent pacemakers or implantable cardioverter-defibrillators who develop Staphylococcus aureus bacteremia (SAB). METHODS AND RESULTS: A cohort of all adult patients with SAB and permanent pacemakers or implantable cardioverter-defibrillators over a 6-year period was evaluated prospectively. The overall incidence of confirmed CDI was 15 of 33 (45.4%). Confirmed CDI occurred in 9 of the 12 patients (75%) with early SAB (<1 year after device placement). Fifteen of 21 patients (71.5%) with late SAB (>/=1 year after device placement) had either confirmed (6 of 21, 28.5%) or possible (9 of 21, 43%) CDI. In 60% of the patients (9 of 15) with confirmed CDI, no local signs or symptoms suggesting generator pocket infection were noted. CONCLUSIONS: The incidence of CDI among patients with SAB and cardiac devices is high. Neither physical examination nor echocardiography can exclude the possibility of CDI. In patients with early SAB, the device is usually involved, and approximately 40% of these patients have obvious clinical signs of cardiac device involvement. Conversely, in patients with late SAB, the cardiac device is rarely the initial source of bacteremia, and there is a paucity of local signs of device involvement. The cardiac device is involved, however, in >/=28% of these patients.

Prospective analysis of Staphylococcus aureus bacteremia in nonneutropenic adults with malignancy.

PURPOSE: To determine the primary sources and secondary complications of Staphylococcus aureus bacteremia (SAB) in cancer patients, as well as predictors of outcome in cancer patients with SAB. PATIENTS AND METHODS: Fifty-two patients at Duke University Medical Center met entry criteria between September 1994 and December 1996 for this prospective cohort study involving hospitalized nonneutropenic adult cancer patients with SAB. All subjects were observed throughout initial hospitalization and were evaluated again at 6 and 12 weeks or until death. RESULTS: SAB was intravascular device-related in 42%, tissue infection-related (TIR) in 44%, and unidentifiable focus-related (UFR) in 13%. Seventeen patients (33%) were found to have metastatic infections or conditions, with eight (15%) developing infectious endocarditis (IE). Patients with TIR bacteremia were less likely than other patients to develop IE (4% v 24%, P =.06). The overall mortality rate was 38%, the SAB-related mortality rate was 15%, and the rate of SAB relapse was 12%. Methicillin resistance was not associated with adverse outcome. Inability to identify a point of entry (UFR bacteremia), however, was associated with a higher overall mortality rate (100% v 24%, P =.0006). Furthermore, a 72-hour surveillance blood culture positive for organisms was associated with an increased incidence of IE (P =.0006), metastatic infections or conditions (P =.0002), SAB relapse (P =.038), and SAB-related death (P =.038). CONCLUSION: SAB in cancer patients is associated with significant morbidity from frequent metastatic infections or conditions including IE, as well as considerable mortality. Unknown initial infection site and 72-hour surveillance cultures positive for organisms were predictive of a complicated course and poor final outcome.

Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients.

OBJECTIVES: The purpose of this prospective study was to examine the role of echocardiography in patients with Staphylococcus aureus bacteremia (SAB). BACKGROUND: The reported incidence of infective endocarditis (IE) among patients with SAB varies widely. Distinguishing patients with uncomplicated bacteremia from those with IE is therapeutically and prognostically important, but often difficult. METHODS: One hundred-three consecutive patients undergoing both transthoracic (TTE) echocardiography and transesophageal (TEE) echocardiography were prospectively evaluated. All patients presented with fever and > or = 1 positive blood culture and were followed up for 12 weeks. RESULTS: Although predisposing heart disease was present in 42 patients (41%), clinical evidence of infective endocarditis (IE) was rare (7%). TTE revealed anatomic abnormalities in 33 patients, but vegetations in only 7 (7%), and was considered indeterminate in 19 (18%). TEE identified vegetations in 22 patients (aortic valve in 5, mitral valve in 9, tricuspid valve in 4, catheter in 2 and pacemaker in 2, abscesses in 2, valve perforation in 1 and new severe regurgitation in 1; 26 total [25%]). Using Duke criteria for the diagnosis of IE, definite IE was present in 26 patients (25%). Clinical findings and predisposing heart disease did not distinguish between patients with and without IE. The sensitivity of TTE for detecting IE was 32%, and the specificity was 100%. The addition of TEE increased the sensitivity to 100%, but resulted in one false positive result (specificity 99%). TEE detected evidence of IE in 19% of patients with a negative TTE and 21% of patients with an indeterminate TTE. At follow-up, cure of staphylococcal infection occurred in a similar percentage of patients with and without IE (77% and 75%, respectively). However, death due to sepsis was significantly more likely among patients with IE (4 of 26 [15%]) than among those without IE (2 of 77 [3%]) (p = 0.03). CONCLUSIONS: Our results suggest that IE is common among patients admitted to the hospital with SAB and is associated with an increased risk of death due to sepsis. TEE is essential to establish the diagnosis and to detect associated complications. Therefore, the test should be considered part of the early evaluation of patients with SAB.

Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database.

PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.

Gonococcal osteomyelitis. Case report and review of the literature.

We report the 11th case of gonococcal osteomyelitis in the postantibiotic era. This case demonstrates the classic presentation of osteomyelitis associated with gonorrhea, a subacute illness with minimal systemic symptoms. In addition, we present radiologic evidence of the pathogenesis of this unusual osteomyelitis from a contiguous joint infection.

Cranial computed tomography before lumbar puncture: a prospective clinical evaluation.

OBJECTIVE: To prospectively identify which patients can safely undergo lumbar puncture (LP) without screening cranial computed tomography (CT). METHODS: Emergency department physicians examined patients before CT. Examiners recorded the presence or absence of 10 clinical findings and answered 8 additional questions. The criterion standard was noncontrast cranial CT interpreted by staff radiologists. Clinical findings were prospectively compared with those of CT. RESULTS: One hundred thirteen consecutive adults with the urgent need for LP (median age, 42 years) were studied. Fifteen percent of patients meeting entrance criteria had new CT-documented lesions, with 2.7% having lesions that contraindicated LP. Sensitivity, specificity, and likelihood ratios (LRs) were measured for the clinical findings. Three statistically significant predictors of new intracranial lesions were identified: altered mentation (positive LR, 2.2; 95% confidence interval [CI], 1.5-3.2), focal neurologic examination (positive LR, 4.3; 95% CI, 1.9-10), and papilledema (positive LR, 11.1; 95% CI, 1.1-115). No single item adequately predicted the absence of CT abnormalities, but the clinical screening items in aggregate significantly predicted the results (negative LR, 0; upper 95% confidence limit, 0.6). The overall clinical impression had the highest predictive value in identifying patients with CT-defined contraindications to LP (positive LR, 18.8; 95% CI, 4.8-43). CONCLUSIONS: Because of the low prevalence of lesions that contraindicate LP, screening cranial CT solely to establish the safety of performing an LP typically provides limited additional information. Physicians can use their overall clinical impression and 3 clinical predictors to identify patients with the greatest risk of having intracranial lesions that may contraindicate LP.

Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis.

OBJECTIVE: The objective was to conduct a systematic review and network meta-analysis (NMA) of existing treatments for ABSSSI focusing on the novel lipoglycopeptide oritavancin. METHODS: EMBASE, MEDLINE, MEDLINE in Process, CENTRAL (Cochrane), and select conferences were searched for randomized controlled trials investigating antimicrobial agents for the treatment of ABSSSI. NMA was used to estimate the odds ratios of the Test-Of-Cure (TOC) and Early Clinical Response (ECR) outcomes for treatments relative to vancomycin in the ITT populations. Sub-group analyses in MRSA and MSSA populations were conducted for TOC; sensitivity analyses investigated the use of the clinically evaluable (CE) populations and the restriction to trials following the recent FDA guidelines for clinical trials. RESULTS: The systematic review identified 52 trials. The most commonly investigated treatments were vancomycin and linezolid; most trials reported TOC, but not ECR. The posterior mean and 95% credible intervals for odds ratios of TOC for antimicrobial agents relative to vancomycin were: linezolid (1.55; 0.91-2.57), daptomycin (2.18; 0.90-5.42), and oritavancin 1200 mg (1.06; 0.80-1.43). The odds ratio of ECR for oritavancin 1200 mg was 1.02 (0.23-4.33). In the MRSA sub-group the odds ratios relative to vancomycin for TOC were: linezolid (1.55; 0.96-2.46), daptomycin (0.74; 0.13-3.66), and oritavancin 1200 mg (0.94; 0.44-2.02). In the MSSA sub-group they were linezolid (1.36; 0.15-13.34) and oritavancin 1200 mg (0.82; 0.08-7.83). These results were robust to the sensitivity analyses. CONCLUSIONS: This NMA provides a unified framework for the comparison of all available antimicrobial agents used in the treatment of ABSSSI and is the first to assess the ECR end-point. The results suggest equivalence of clinical efficacy between vancomycin, daptomycin, linezolid, and novel antimicrobial agents including oritavancin for the treatment of ABSSSI at TOC. The wide uncertainty margins indicate the heterogeneity of the available evidence and the need for further research.

Prognostic factors in 61 cases of Staphylococcus aureus prosthetic valve infective endocarditis from the International Collaboration on Endocarditis merged database.

Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with a high mortality rate, but prognostic factors have not been clearly elucidated. The International Collaboration on Endocarditis merged database (ICE-MD) contained 2212 cases of definite infective endocarditis (as defined using the Duke criteria), 61 of which were SA-PVIE. Overall mortality rate was 47.5%, stroke was associated with an increased risk of death, and early valve replacement was not associated with a significant survival benefit in the whole population; however, patients who developed cardiac complications and underwent early valve replacement had the lowest mortality rate (28.6%).

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Cytomegalovirus infection in the normal host.

CMV mononucleosis often resembles EBV infectious mononucleosis; however, certain features of the history and physical may help to distinguish CMV from EBV. While CMV mononucleosis is usually self-limited, certain laboratory abnormalities may persist for months or years after the patient has recovered. Previous reports on CMV in the non-immunocompromised host have rarely described systemic complications. We have reviewed 10 cases of CMV with systemic manifestations at one institution over a 15-year period. These patients had prolonged fevers (often greater than three weeks) and the diagnosis was often unsuspected during the early part of the illness. While two patients required mechanical ventilation, all patients had self-limiting disease and survived. When CMV is suspected and diagnosed early in the course, numerous diagnostic (and potentially dangerous) tests can be avoided in a viral illness in which prolonged fever is common.

Extra-intestinal manifestations of salmonella infections.

While salmonellosis is often considered to affect primarily the gastrointestinal tract, infection at other sites may occur, producing characteristic clinical syndromes. We reviewed cases from our institutions and the literature on focal manifestations of salmonella infections. In the past, most extra-intestinal salmonella infections were caused by S. choleraesuis; however, we found S. typhimurium to be the predominant serotype. The mortality rate for patients in our series was considerably lower than the rate described for focal infections in other reviews. This may in part be due to lower proportion of infections due to S. choleraesuis, improved microbiologic and diagnostic techniques, increased use of ampicillin, and improved surgical techniques. Salmonella endocarditis usually occurs in patients with preexisting heart disease. Unlike other salmonella infections, S. choleraesuis is the most frequent serotype. Salmonella endocarditis is often very destructive, with a fatality rate of 70%. Nonvalvular (mural) endocarditis occurs in one-fourth of patients and survival has not been reported. While antibiotic therapy should be tried initially, if response is not prompt the clinician should look for an associated site of infection (intra- or extra-cardiac abscess), which will often require surgery. Salmonella pericarditis often presents with cardiac or pulmonary symptoms, but typical signs of pericardial disease (pulsus paradoxus, friction rub) or characteristic electrocardiographic changes (low voltage, elevated ST segments) are uncommon. Early diagnosis, before infection involves other areas of the heart, is crucial for survival. In addition to antibiotic therapy, pericardiocentesis or pericardiectomy is required. Salmonella may infect the peripheral or visceral arteries, but the abdominal aorta is the most frequent site of vascular infection. Most patients are men over age 50 with preexisting atherosclerosis of the aorta who do not have a previous history of gastroenteritis. About one-fourth of patients have associated lumbar osteomyelitis. No patients have been reported to survive with medical therapy alone. Specific guidelines for surgical removal of infected aneurysms have been proposed and these (in addition to increased use of ampicillin) may be responsible for higher survival rates in recent years. Due to the high incidence of relapses, postoperative blood cultures should be done routinely. Arterial infection should be considered in any elderly patient with salmonella bacteremia especially with prolonged fever or bacteremia after an "adequate course" of antibiotic therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Gonococcal endocarditis: a new look at an old disease.

Gonococcal endocarditis, like other gonococcal infections, occurs mainly in the young adult population. The onset of the disease tends to be subacute with an infrequent history of preceding infection or the discovery of a local source of infection. The presenting symptoms and signs fail to differentiate it from other types of endocarditis. Blood cultures are often negative for the first several days. Echocardiography has been useful in helping establish a diagnosis, and survival is favorable with medical and surgical therapy if the diagnosis is made early in the course of the disease. The disease can be quite aggressive, however, and lead to rapid clinical deterioration from valvular destruction and congestive heart failure. As with other forms of endocarditis, deterioration is an indication for aggressive management with early valve replacement.

Single and multiple pyogenic liver abscesses. Natural history, diagnosis and treatment, with emphasis on percutaneous drainage.

The presenting features, modes of treatment and clinical course were reviewed for 55 patients with pyogenic liver abscess, seen at Duke University Medical Center over a 15-year period. Thirty-three patients had a solitary abscess and 22 had multiple abscesses. Most patients were between the ages of 40 and 60 years. Males predominated, 2.4:1. Major underlying conditions included biliary tract disease, malignancy and colonic disease. Eight patients, each with a solitary abscess, had no identifiable underlying condition. Symptoms and signs were nonspecific: fever, chills, focal abdominal tenderness and hepatomegaly were common. A raised serum alkaline phosphatase level was the most consistent abnormal laboratory finding. CT with contrast enhancement, radioisotope scanning and ultrasonography all accurately defined solitary hepatic abscesses. However, CT scan was more successful than other imaging techniques in detecting multiple abscesses. In seven patients the diagnosis was made only at laparotomy. Overall, a diagnosis of liver abscess was made in 50 living patients (91%). Microorganisms were recovered from pus and/or blood cultures of 44 patients (80%). Most common were enteric gram-negative facultative rods, anaerobic gram-negative rods, and microaerophilic streptococci. Single abscesses were more likely than multiple abscesses to contain more than one organism. All patients received antibiotics; the choice of antibiotic does not appear to be critical provided the regimen has a broad spectrum including activity against anaerobes. Surgical or percutaneous drainage was successful when attempted in all patients with a single abscess, but the outcome was less favorable in those with multiple abscesses. Percutaneous drainage is currently replacing open operative drainage as the method of choice. Overall mortality in patients with single abscesses was 15% (5/33) and in those with multiple abscesses 41% (9/22).