Tuberculous hepatitis in renal transplant recipients following alemtuzumab induction therapy.

Mycobacterium tuberculosis infection is one of many opportunistic infections in renal transplant recipients, arising either from reactivation of latent infection or de novo infection, occasionally donor derived. M. tuberculosis hepatitis has never been reported in patients who have received alemtuzumab as part of their renal transplant management. We describe 2 patients who underwent deceased-donor renal transplantation following alemtuzumab induction therapy and presented with a febrile syndrome, subsequently diagnosed as tuberculous hepatitis, one with disseminated disease. Both responded well to treatment without significant side effects, resulting in excellent graft function. The importance of chemoprophylaxis should be emphasized to minimize the risk of developing active tuberculosis in patients with latent tuberculosis infection undergoing solid organ transplantation.

Evaluation of risk factors for cytomegalovirus infection and disease occurring within 1 year of liver transplantation in high-risk patients.

BACKGROUND: Recent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high-risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined. METHODS: A retrospective cohort study of 227 high-risk first LTR who received primary anti-CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post-transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P-values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant. RESULTS: CMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end-stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance. CONCLUSION: Our results suggest that interventions designed to prevent CMV infection and disease should be applied to all high-risk LTR until more definitive predictors of these complications are identified.

Association of cytomegalovirus infection and disease with death and graft loss after liver transplant in high-risk recipients.

In the era of effective antiviral chemoprophylaxis, cytomegalovirus (CMV) disease has been inconsistently associated with increased mortality in liver transplant (LT) recipients. A retrospective study evaluating the association of CMV infection and disease occurring within 1 year of transplant with the endpoints of death or the combined endpoint of graft loss or death was undertaken in a cohort of 227 CMV donor seropositive, recipient seronegative first LT recipients. Associations were evaluated using Cox proportional hazards regression models. CMV infection and disease occurred in 91 (40%) and 43 (19%) patients, respectively. Forty-eight (21%) died while 58 (26%) sustained graft loss or death. In multivariable analysis, CMV infection was associated with an increased risk of death (RR: 2.24, p = 0.008) and graft loss or death (RR: 2.85, p < 0.001). CMV disease was also associated with an increased risk of death (RR: 2.73, p = 0.003) and graft loss or death (RR: 3.04, p = 0.001). CMV infection and disease occurring within the first year after LT in high-risk recipients is associated with increased risk of death and of graft loss or death. Investigation of strategies to further reduce the risk of CMV infection and disease in high-risk LT recipients is warranted.

Association of surgeon with surgical site infection after liver transplantation.

Surgical site infection (SSI) after liver transplantation has been associated with increased risk of allograft loss and death. Identification of modifiable risk factors for these infections is imperative. To our knowledge, intraoperative practices associated with transplant surgeons have not been assessed as a risk factor. A retrospective cohort study of risk factors for SSI after 1036 first liver transplantations completed by seven surgeons at a single center between 2003 and 2008 was undertaken. Cox proportional hazards models were used to evaluate the association between surgeons and SSIs. SSIs were identified in 166 of 1036 patients (16%). Single variable analysis showed strong evidence of an association between surgeon and SSI (p = 0.0007); the estimated cumulative incidence of SSI ranged from 7% to 24%. This result was consistent in multivariable analysis adjusting for potentially confounding variables (p = 0.002). The occurrence of organ-space or deep SSI varied significantly among surgeons in both single variable analysis (p = 0.005) and multivariable analysis (p = 0.006). These findings provide evidence that differences in the surgical practices of individual surgeons are associated with risk for SSI after liver transplantation. Identification of specific surgical practices associated with risk of SSI is warranted.

Healthcare-associated hepatitis C virus transmission among patients in an abdominal organ transplant center.

BACKGROUND: De novo hepatitis C virus (HCV) infection among transplant patients is rarely recognized but can have severe consequences. We investigated the scope, source, and mode of HCV transmission within a transplant center after incident HCV infection was identified in 2 patients who had liver transplantation in late 2006. METHODS: Patients were interviewed, and transplant logs, medical records, and staff practices were reviewed to identify opportunities for HCV transmission. Infection via receipt of blood or organs was evaluated. Molecular epidemiology was used to determine the relatedness between persons with incident and chronic HCV infection. RESULTS: HCV from infected blood or organ donors was ruled out. Among the 308 patients who underwent transplant in 2006, no additional incident HCV infections were identified. Eighty-five (28%) had pre-transplant chronic HCV infection; 13 were considered possible HCV source patients based upon shared days on the inpatient unit, nursing assignment, or invasive procedures in common with incident HCV case-patients. Viral isolates from 1 HCV source patient and 1 incident case-patient were found to be highly related by quasispecies analysis, confirming patient-to-patient HCV transmission. Possible modes of transmission identified were the improper use of multidose vials, sharing of blood-contaminated glucometers, and touch contamination. CONCLUSION: Sporadic transmission or endemic levels of HCV transmission might be overlooked in a setting with high HCV prevalence, such as liver transplant units, where multiple, repeated opportunities for patient-to-patient HCV transmission can occur. Surveillance through pre- and post-transplant screening is necessary to identify incident HCV infection in this setting. Constant, meticulous attention must be paid to maintaining aseptic technique and good infection control practices to eliminate HCV transmission opportunities.

Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir.

The natural history of cytomegalovirus (CMV) disease associated with solid organ transplantation has been modified as a result of the widespread use of antiviral prophylaxis. Anecdotal reports have indicated a reduction of CMV disease at the expense of its later occurrence after completion of ganciclovir prophylaxis. The present study investigated the occurrence of CMV disease and its risk factors among 37 liver and kidney transplant recipients with CMV D+/R- status who received oral ganciclovir during the first 100 days posttransplantation. CMV disease occurred in 9 patients (24.3%) at a median of 144 days posttransplantation (range, 95-190 days). Allograft rejection was found to be strongly associated with the occurrence of late-onset CMV disease (risk ratio, 6.6; 95% confidence interval, 1.4-32.1; P=.02). Thus, CMV D+/R- solid organ transplant recipients receiving 3 months of oral ganciclovir who develop allograft rejection during the period of antiviral prophylaxis may benefit from extended and/or enhanced antiviral prophylaxis to prevent late-onset CMV disease.

Failure of treatment for chronic Mycobacterium abscessus meningitis despite adequate clarithromycin levels in cerebrospinal fluid.

We report a case of posttraumatic meningitis due to Mycobacterium abscessus, treated initially with oral clarithromycin and intravenous amikacin plus intrathecal amikacin. Despite cerebrospinal fluid (CSF) levels of clarithromycin and amikacin in excess of their in vitro minimum inhibitory concentrations for the organism, the CSF cultures remained continuously positive for M. abscessus. To our knowledge, this is the first documented case of M. abscessus meningitis and the first report of measured CSF levels of clarithromycin in a patient with meningitis, showing that even therapeutic CSF levels of clarithromycin and amikacin might not be successful in eradicating M. abscessus meningitis.

Confronting the problem of increasing antibiotic resistance.

Significant increases in prevalence of resistance to antibiotics have been observed in common pathogens of humans in the United States and worldwide. The consequences of the appearance and spread of antibiotic resistance have included increasing morbidity, mortality, and cost of health care. The fundamental cause for the appearance and spread of antimicrobial resistance has been increasing antimicrobial use. However, other factors contribute in both inpatient and outpatient settings. Recognizing the important causes of increasing antibiotic resistance in these settings has led to practical recommendations, which health care facilities and outpatient practitioners will need to review, adapt, and apply for maximum local effectiveness for progress to be made in addressing one of the most challenging problems facing modern medicine.

Vertebral Aspergillus osteomyelitis and acute diskitis in patients with chronic obstructive pulmonary disease.

Aspergillus osteomyelitis of the spine with acute diskitis has been well documented in immunocompromised hosts but is rare in immunocompetent patients. Predisposing factors to infection are prolonged neutropenia, hematologic malignancies, chemotherapy, history of prior spinal trauma or surgery, allograft transplantation, or any condition requiring the use of long-term immunosuppressive agents or systemic corticosteroids. Patients with chronic obstructive pulmonary disease (COPD) treated with systemic corticosteroids for either long-term management or frequent exacerbations are at potential risk for such infections. Patients with severe COPD treated primarily with inhaled corticosteroids are considered immunocompetent. This report describes 2 cases of Aspergillus osteomyelitis with acute diskitis in apparently immunocompetent patients with COPD who, aside from brief courses of systemic corticosteroids, were using inhaled corticosteroid therapy. One patient was treated with intravenous amphotericin B alone, whereas the other received amphotericin B and underwent surgical debridement. Both have done well and were symptom free at 6-month follow-up.

Carbapenems and monobactams: imipenem, meropenem, and aztreonam.

Imipenem and meropenem, members of the carbapenem class of beta-lactam antibiotics, are among the most broadly active antibiotics available for systemic use in humans. They are active against streptococci, methicillin-sensitive staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas. Resistance to imipenem and meropenem may emerge during treatment of P. aeruginosa infections, as has occurred with other beta-lactam agents; Stenotrophomonas maltophilia is typically resistant to both imipenem and meropenem. Like the penicillins, the carbapenems have inhibitory activity against enterococci. In general, the in vitro activity of imipenem against aerobic gram-positive cocci is somewhat greater than that of meropenem, whereas the in vitro activity of meropenem against aerobic gram-negative bacilli is somewhat greater than that of imipenem. Daily dosages may range from 0.5 to 1 g every 6 to 8 hours in patients with normal renal function; the daily dose of meropenem, however, can be safely increased to 6 g. Infusion-related nausea and vomiting, as well as seizures, which have been the main toxic effects of imipenem, occur no more frequently during treatment with meropenem than during treatment with other beta-lactam antibiotics. The carbapenems should be considered for treatment of mixed bacterial infections and aerobic gram-negative bacteria that are not susceptible to other beta-lactam agents. Indiscriminate use of these drugs will promote resistance to them. Aztreonam, the first marketed monobactam, has activity against most aerobic gram-negative bacilli including P. aeruginosa. The drug is not nephrotoxic, is weakly immunogenic, and has not been associated with disorders of coagulation. Aztreonam may be administered intramuscularly or intravenously; the primary route of elimination is urinary excretion. In patients with normal renal function, the recommended dosing interval is every 8 hours. Patients with renal impairment require dosage adjustment. Aztreonam is used primarily as an alternative to aminoglycosides and for the treatment of aerobic gram-negative infections. It is often used in combination therapy for mixed aerobic and anaerobic infections. Approved indications for its use include infections of the urinary tract or lower respiratory tract, intra-abdominal and gynecologic infections, septicemia, and cutaneous infections caused by susceptible organisms. Concurrent initial therapy with other antimicrobial agents is recommended before the causative organism has been determined in patients who are seriously ill or at risk for gram-positive or anaerobic infection.

Assessment of routine use of an anaerobic bottle in a three-component, high-volume blood culture system.

The relative value of routine anaerobic blood culture for recovery of organisms and identification of episodes of bloodstream infection was assessed in a three-component, high-volume blood culture system which employs aerobic and anaerobic bottles of BacT/Alert (Organon-Teknika, Durham, N.C.) and aerobic cultures of Isolator (Wampole Laboratories, Cranbury, N.J.). The results of 5,595 blood culture sets from patients with suspected bloodstream infection were analyzed. Compared with either the aerobic BacT/Alert bottle or aerobic culture of Isolator, the BacT/Alert anaerobic bottle recovered significantly fewer isolates (242 versus 294, P < 0.05; 242 versus 298, P < 0.05) but did not detect significantly fewer episodes of bloodstream infection (141 versus 157, P > 0.05; 141 versus 147, P > 0.05). The BacT/Alert anaerobic bottle recovered significantly more isolates of obligately anaerobic bacteria (16 versus 4, P < 0.05; 16 versus 0, P < 0.05) and detected significantly more episodes of bloodstream infection caused by obligately anaerobic bacteria (10 versus 3, P < 0.05; 10 versus 0, P < 0.05) than either the aerobic bottle of BacT/Alert or the aerobic culture of Isolator. The combination of the BacT/Alert anaerobic bottle and the aerobic culture of Isolator recovered as may isolates (374 versus 377) and detected as many episodes of bloodstream infection (194 versus 191) as the combination of the aerobic bottle of BacT/Alert and the aerobic culture of Isolator, and both of these combinations identified at least 8% more isolates and detected at least 3% more bloodstream infections than the combination of the BacT/Alert aerobic and anaerobic bottles. Further analysis of the data revealed that the utility of the BacT/Alert anaerobic bottle, especially when combined with the aerobic culture of Isolator, resulted from not only enhanced recovery of obligately anaerobic bacteria but also effective recovery of facultatively anaerobic bacteria. These results demonstrate the utility of the anaerobic BacT/Alert bottle for detecting bloodstream infection caused by either facultatively anaerobic bacteria or obligately anaerobic bacteria and support the routine inclusion of anaerobic blood culture in the three-component blood culture system used in our hospital.

Vascular and other serious infections with Mycobacterium bovis after bacillus of Calmette-Guérin therapy for bladder cancer.

Intravesical application of bacillus of Calmette-Guérin (BCG) has proved to be an effective form of treatment for some stages of bladder cancer. Infrequent, serious complications of this treatment have become apparent as its use has become more widespread. We report a case of Mycobacterium bovis mycotic abdominal aortic aneurysm and a case of M. bovis mycobacteremia that developed as complications of intravesical BCG therapy. These cases are discussed in the context of a review of reported complications of intravesical BCG therapy and a review of measures currently advocated to prevent them.

Localized soft-tissue infections with Mycobacterium avium/Mycobacterium intracellulare complex in immunocompetent patients: granulomatous tenosynovitis of the hand or wrist.

In immunocompetent patients, Mycobacterium avium/Mycobacterium intracellulare complex (MAC) has been associated with pulmonary infection in adults, cervical lymphadenitis in children, and disseminated infection in children and adults. MAC rarely has been recognized as a cause of localized soft-tissue infection in immunocompetent hosts. Six cases of granulomatous tenosynovitis due to MAC are reported; five cases occurred after local surgical procedures, trauma, or corticosteroid injection. In four cases, cure was achieved with combined medical and surgical intervention. In these six cases and 11 previously reported cases, both males and females were affected equally, usually in the fifth to seventh decades of life, and the distal upper extremity was predominantly involved. Surgical debridement with appropriate culture was critical for diagnosis and management. Antimycobacterial chemotherapy seemed to be a beneficial adjunctive measure in most cases but was clearly necessary for cure in only a few cases.

Clinical comparison of the isolator and BacT/Alert aerobic blood culture systems.

The performance characteristics of the Isolator (Wampole Laboratories, Cranbury, N.J.) and the BacT/Alert (Organon Teknika Corporation, Durham, N.C.) aerobic blood culture systems were compared for 6,009 blood culture sets obtained from patients with suspected bloodstream infections. The BacT/Alert aerobic bottle [BTA(O2)] was continuously agitated while it was incubated in 5% CO2 at 36 degrees C; culture plates prepared from the Isolator tube [I(O2)] were incubated in 5% CO2 at 37 degrees C. From 394 blood cultures, 416 clinically significant isolates of bacteria and yeasts were recovered. The overall yields for BTA(O2) and I(O2) were not significantly different (319 versus 336; P = 0.20). I(O2) recovered significantly more staphylococcus (P < 0.05) and yeast isolates (P < 0.01). BTA(O2) recovered significantly more aerobic and facultatively anaerobic gram-negative bacilli (P < 0.05). In blood culture sets which produced growth of the same organisms in both the BTA(O2) and I(O2) systems, the BTA(O2) system detected growth sooner, but more rapid identification was possible with the I(O2) system by virtue of earlier isolation of colonies on solid media.

Cholera in the United States.

Cholera remains a threat to human health in many parts of the world, including the United States. The epidemiology of cholera is reviewed to prepare for identification and prevention of the disease in appropriate clinical settings. The clinical manifestations of cholera and the pathophysiology of the toxin-induced diarrhea are reviewed to introduce and to clarify appropriate therapeutic and preventive interventions.

Varicella-zoster virus retinitis in a patient with AIDS-related complex: case report and brief review of the acute retinal necrosis syndrome.

Retinitis reminiscent of the acute retinal necrosis syndrome was recognized in a patient with AIDS-related complex after he had experienced several episodes of a sacral, dermatomic zosteriform eruption. Varicella-zoster virus (VZV) was subsequently recovered from cell culture of retinal tissue. The literature on VZV retinitis, including that on acute retinal necrosis, is reviewed. Dissemination of VZV infection in AIDS is also reviewed. Features that differentiate the findings and course of VZV retinitis in patients with AIDS from those in otherwise healthy adults are noted and related to potentially different pathogenic mechanisms. This unusual and recently recognized complication of herpesvirus infection may be promoted by AIDS-related immunosuppression. Acute retinal necrosis and other more-recently described forms of VZV retinitis, which have primarily been subjects of the ophthalmologic literature, merit the attention of clinicians and investigators of infectious diseases.

Continuous intravenous versus intermittent ampicillin therapy of experimental endocarditis caused by aminoglycoside-resistant enterococci.

We studied the efficacy of continuous intravenous infusion of ampicillin compared with that of intermittent administration of ampicillin alone or in combination with gentamicin for the therapy of highly aminoglycoside-resistant enterococcal experimental endocarditis. Rabbits were infected with a gentamicin-susceptible (MIC, 256 micrograms/ml) strain of Enterococcus faecalis or a strain of E. faecalis which was highly resistant to gentamicin in vitro (MIC, greater than 2,000 micrograms/ml). Administration of ampicillin by continuous intravenous infusion did not significantly enhance the killing of enterococci in vivo compared with that by intermittent administration of ampicillin for either the aminoglycoside-susceptible or the aminoglycoside-resistant strain. In combination with gentamicin, there were no significant differences in efficacies obtained with intermittent versus continuous intravenous infusion of ampicillin therapy for experimental endocarditis caused by either strain of E. faecalis.