Jack M. Bernstein

Chronic wound infection: Facts and controversies

Chronic wound infections are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Wound infection may initially be manifest as bacterial colonization, and it is only when colonization is combined with other factors, such as decreased vascular supply, intrinsic virulence of specific bacteria (eg, Staphylococcus aureus), and host immune factors, that true infection occurs. The microbiology of chronic wounds is complex, and it is difficult to discern which bacteria are culpable. Deep cultures or quantitative biopsies of wound tissue may be necessary. In some instances, such as in the presence of certain mycobacteria, isolation of specific organisms confirms causation. In many instances, it is appropriate to treat these wounds empirically with a combination of topical antiseptics and systemic antibiotics, especially in the presence of invasive infections.

Active respiratory syncytial virus purified by ion-exchange chromatography : characterization of binding and elution requirements

Two viruses, respiratory syncytial virus (RSV) and vesicular stomatitis virus (VSV) were used to evaluate viral purification by an affinity resin column (Matrex Cellufine Sulfate (MCS); Amicon Division, WR Grace & Co.). Viable RSV was purified significantly from crude cell lysate by a single pass through a column containing the anionic MCS resin. Most cell protein and albumin eluted from the MCS resin with phosphate buffered saline (PBS) but RSV eluted at high ionic strength, i.e., greater than or equal to 0.6 M NaCl. Further purification was possible by sucrose step gradient centrifugation. The RSV prepared by column purification or by column plus sucrose gradient separation was both intact and infective. RSV and pure samples of VSV were used to optimize ionic strength and salts for elution from the MCS column: 0.8 M NaCl removed most of the viral protein. The capacity of the MCS gel for RSV or VSV was found to be about 0.6-0.8 mg viral protein per ml of hydrated resin. Detergent-solubilized viral membrane proteins bound to the MCS resin in 0.145 M NaCl and eluted with higher salt concentrations. Thus, this resin also may be a useful aid for relatively gentle purification of these proteins.

Lactobacillus paracasei Continuous Ambulatory Peritoneal Dialysis-Related Peritonitis and Review of the Literature

ABSTRACT We describe the first case of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis due to Lactobacillus paracasei. It occurred in a 65-year-old patient with recurrent episodes of peritonitis while he was receiving a prolonged course of intraperitoneal vancomycin. L. paracasei should be considered in the differential diagnosis of pathogens in CAPD-related peritonitis, especially in patients receiving prolonged vancomycin or glycopeptide treatment.

Choice of antibiotics, pharmacokinetics, and dose adjustments in acute and chronic renal failure.

A multitude of antimicrobial agents have become available over the past two decades. Appropriate use of these drugs demands not only an understanding of the antimicrobial spectrum of the agent but of the necessary dose adjustments because of renal or hepatic impairment. The use of computer-assisted pharmacokinetic modeling for dosing potentially toxic drugs such as aminoglycosides and vancomycin should be utilized whenever possible.

A comparison of netilmicin and tobramycin therapy in patients with renal impairment

We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function.

Comparison of oral and aerosol ribavirin regimens in the high risk elderly

A comparison of different regimens of ribavirin (R), administered either orally or by aerosol, was performed in 16 elderly subjects (13 men, 3 women, mean age 63 ± 8 years) considered to be in the “high‐risk” category for complications from influenza as defined by the Centers for Disease Control. The subjects were divided into four groups. Group O‐600 received 600 mg orally R every 8 hours for 48 hours followed by 200 mg every 8 hours for 72 hours for a total dose of 5.4 g (22.1 mmol). Group O‐800 received 800 mg oral R every 8 hours for 24 hours followed by 400 mg every 12 hours for 96 hours for a total dose of 4.1 g (22.9 mMoles). Group A‐40 received R (40 mg/ml) aerosolized through a small particle aerosol generator for 6 hours every 12 hours for 96 hours, yielding an average delivered dose of 6.2 g (25.4 mMoles) R. Group A‐60 received aerosolized R (60 mg/mL) for 2 hours every 8 hours for 96 hours, yielding an average delivered dose of 4.6 g (18.8 mMoles) R. No hematologic or other laboratory abnormalities were associated with any of the regimens. Group O‐800 and O‐600 reached mean peak plasma R levels of 11.8 μM and 5.3 μM, respectively, after 18 hours of therapy. Subsequent administration of 20 mg R every 8 hours was sufficient to maintain a plasma R level greater than 7 μM. Among the aerosol groups, group A‐40 approached steady state plasma R levels (8–10 μM) more quickly than group A‐60. Steady state levels could be maintained by administering 60 mg/ml aerosol R for 2 hours, every 8 hours. No adverse pulmonary effects were noted in any patient. Further trials evaluating the clinical efficacy of oral and aerosol ribavirin in the elderly should be carried out.

Healthcare-associated Legionnaires’ disease: Limitations of surveillance definitions and importance of epidemiologic investigation:

Healthcare-associated Legionnaires’ disease (HCA LD) causes significant morbidity and mortality, with varying guidance on prevention. We describe the evaluation of a case of possible HCA LD and note the pitfalls of relying solely on an epidemiologic definition for association of a case with a facility. Our detailed investigation led to the identification of a new Legionella pneumophila serogroup 1 sequence type, confirmed a healthcare association and helped build the framework for our ongoing preventive efforts. Our experience highlights the role of routine environmental cultures in the assessment of risk for a given facility. As clinicians increasingly rely on urinary antigen testing for the detection of L. pneumophila, our investigation emphasises the importance of clinical cultures in an epidemiologic investigation.

A rare presentation of pulmonary hemorrhage with hepatitis C-associated cryoglobulinemia and membranoproliferative glomerulonephritis

Cryoglobulinemia (CG)-associated pulmonary hemorrhage is an unusual entity. An even rarer occurrence is that of membranoproliferative glomerulonephritis (MPGN) in a patient with CG and alveolar hemorrhage. As far as we can tell, there has been no more than a total of four such cases that have been formally published, and this would be the fifth case [1,2]. A 46-year-old Caucasian woman presented to the emergency department with acute respiratory failure, petechiae, pulmonary hemorrhage, azotemia, proteinuria, and hematuria for 10 days. A ventilation/perfusion lung scan was read as low probability for a pulmonary embolism. Additional serologic examinations included negative ANA, anti-GBM, pANCA, cANCA, hepatitis B and HIV antibody. SPEP (serum protein electrophoresis) was also unremarkable. Hepatitis C antibody was positive, and quantitative testing for CG revealed type II (mixed CG, 0.2 g/dL). C3 and C4 complement levels were low. Renal biopsy revealed MPGN. Bronchoscopy did not demonstrate any endobronchial abnormality. The patient was treated with intravenous methylprednisolone, and both hemoptysis and renal function improved. She did not return for follow-up care. CG associated with HCV has been recognized to cause pulmonary complications which are usually mild and without any significant signs or symptoms. Alveolar hemorrhage in CG is rare; there have been only 10 case reports in English medical literature [1]. Patients with the cryoglobulinemic pulmonary hemorrhage have an extremely poor prognosis and high mortality at presentation and even a poorer prognosis in survivors having further hemorrhagic episodes [1]. Diagnosis of pulmonary hemorrhage associated with HCV-associated CG requires a high index of suspicion; in this case, the patient presented to the emergency services with severe respiratory insufficiency and bilateral alveolar infiltrates on chest radiograph. Her acute respiratory decompensation with diffuse alveolar infiltrates and hemoptysis is indicative of alveolar hemorrhage syndrome [3]. The diagnosis can also be confirmed with the demonstration of hemosiderophages in alveolar lavage obtained by bronchoscopy. It has been established that patients with CG with chronic infection by HCV are sometimes linked to membranoproliferative glomerulonephritis with a survival rate of 33–49% after a mean follow-up of 10 years. Managing an autoimmune manifestation of an infectious disease is complex. Although immunosuppressive agents may be needed to control potentially life-threatening autoimmune complications, there is a risk that the infection might get worse. A reasonable approach is first to control the acute autoimmune manifestations of disease with immunosuppressive therapy and then to deal with the underlying infection to prevent relapse [3]. We conclude that both alveolar hemorrhage and renal involvement associated with HCV-related type CG are exceptional entities. This poses problems regarding treatment as each patient may need a tailored treatment [1]. Conflict of interest statement. None declared.