Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients.

We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.

Sore throat in adults--does the introduction of a clinical scoring system improve the management of these patients in a secondary care setting?

OBJECTIVE: To audit sore throat management in adults, introduce proforma-based guidelines and to re-audit clinical practice. SETTING: Adult emergency department of an inner city teaching hospital. METHODS: A literature search was carried out to identify relevant guidelines. In stage one, patients presenting to the emergency department with sore throat were identified retrospectively from the emergency department attendance register. Proformas were completed retrospectively. In stage two, new guidelines were introduced and staff educated about the guidelines. In stage three, patients presenting with sore throat were identified at triage and proformas were completed at time of consultation. OUTCOME MEASURES: (1) appropriate clinical assessment of the likelihood of bacterial infection using the clinical scoring system, (2) appropriateness of antibiotic prescription, (3) recommendation of supportive treatments to patients. RESULTS: Introduction of a clinical scoring system reduced the inappropriate prescribing of antibiotics from 44 per cent to 11 per cent. Correct antibiotic prescription rose from 60 per cent to 100 per cent. Although the variety of advice given about supportive treatment increased, the actual number of patients receiving documented supportive advice fell from 67.8 per cent in stage one to 58 per cent in stage three. CONCLUSION: The introduction of clinically based guidelines for the diagnosis and management of sore throat in adults can reduce inappropriate antibiotic prescribing.

Treatment of community-acquired pneumonia--IDSA guidelines. Infectious Diseases Society of America.

The Infectious Diseases Society of America (IDSA) has published guidelines for the treatment of community-acquired pneumonia (CAP). Although Streptococcus pneumoniae remains the most common etiologic agent, Chlamydia pneumoniae and Legionella pneumophila are also important causes. For all suspected CAP patients, particularly those requiring hospitalization, chest radiographs are strongly recommended to confirm the diagnosis. The IDSA guidelines, in contrast to those published by the American Thoracic Society, emphasize the use of sputum Gram's stain and culture in all patients, whenever possible, to establish etiology. This information can be used not only to guide therapy but also to track trends in the etiologic pathogens for CAP and their antibiotic susceptibility. In light of the better outcomes with the earliest possible interventions, the IDSA recommends initial empiric antimicrobial therapy until laboratory results can be obtained to guide more specific therapy. Macrolides, doxycycline, and fluoroquinolones are suggested for primary empiric therapy, since each has activity against common bacterial pathogens and atypical agents. Detailed antibiotic recommendations are made for various pathogens. For inpatients, attempts should be made to cover Legionella and other common pathogenic bacteria. Alternative antibiotics are recommended for patients with structural diseases of the lung, penicillin allergy, or suspected aspiration pneumonia. Switch to an appropriate oral antibiotic is recommended as soon as the patient's condition is stable and he or she can tolerate oral therapy, often within 72 h.

The microbial ecology and immunology of the adenoid: implications for otitis media.

The nasopharyngeal tonsil, or adenoid, is a major inductive site for the synthesis of J-chain-positive B cells that may migrate to other areas of the upper respiratory tract, such as the nasal mucosa, the parotid gland, the lacrimal gland, and the middle ear during inflammation. The production of secretory IgA by both the nasopharyngeal tonsil and the nasal mucosa plays a major role in local immune protection against bacteria and viruses. The release of cytokines from Th1 and Th2 lymphocytes must be appropriate for B cells to produce IgA. The factors or mechanisms responsible for this are not, at present, known, but it appears that there is a difference in the profiles of cytokine secretion by Th1 and Th2 lymphocytes in the adenoids in both otitis-prone, as well as nonotitis-prone children. We have suggested that if this specific immune system does not protect the host from invasion by potential pathogens, there are other modalities of therapy to protect the nasopharynx from colonization with pathogenic bacteria or viruses. These include the production of specific antibodies against bacterial surface proteins that have been identified as mucin-binding proteins. Alteration of the microbial flora with commensal organisms such as viridans streptococci can be utilized. These alpha-hemolytic streptococci probably function by producing an acid environment that prevents colonization of organisms such as nontypeable H. influenzae. Finally, the induction of specific SIgA by conserved outer membrane protein antigens of potential pathogens may be another strategy in the prevention of colonization of potential bacterial pathogens in the nasopharynx.

The effect of biliary obstruction on a gram-negative bacteremic challenge: a preliminary report.

Alterations in the sequestration and destruction of bacteria were studied after 10 days of biliary obstruction. Intraperitoneal injection of radiolabeled Escherichia coli was used to study bacterial localization in rats 10 days after common duct ligation and transection or sham celiotomy. Animals were sacrificed 4 hours later and uptake by liver, spleen, lung, and kidney were studied with a scintillation counter. No significant difference in localization between the two groups was noted. Bacteremia was induced in a second set of animals and quantitative bacterial organ cultures were performed. Significantly more viable organisms were identified in lung, liver, and kidney of animals that underwent common duct ligation and transection, when compared with controls that underwent sham celiotomy. This suggests that there is a defect in bacterial killing after 10 days of biliary obstruction. The inability to effectively clear and kill gram-negative bacteria in patients with biliary obstruction may account for some of the clinical complications seen in this patient population.

Hepatic trauma. A review of 56 consecutively treated patients.

The records of 56 consecutively treated patients with hepatic trauma were reviewed for clinical features, treatment, and results. Nonpenetrating trauma was the cause of 60% of the injuries, 40% of which were considered major. Peritoneal irritability, hypotension, and a positive abdominal paracentesis were common findings leading to abdominal exploration. Prompt fluid resuscitation followed by operation was successful in most patients. Various suture techniques were effectively used to control hemorrhage, and extensive debridement short of lobectomy was used if possible. Drainage was effective in reducing postoperative complications. Death was associated with extensive injuries that required right hepatic lobectomy in two patients, and in three patients deaths were unrelated to the hepatic injury. Complications were predominantly pulmonary problems, sepsis, and hemorrhage. These results support the prompt operative management of hepatic injuries with accepted procedures of debridement, precise vascular and biliary control, and drainage, conserving hepatic tissues.

Management of lymph fistula in the groin after arterial reconstruction.

Leakage of lymph from the inguinal incision is a rare but disturbing complication of arterial surgery. This article describes our experience in the management of 12 patients in whom lymphorrhea developed following arterial reconstruction. Seven patients were treated with pressure dressings, antibiotics, and immobilization. In this group, fistula healing was delayed up to four weeks, and wound infection occurred in three of seven patients. One patient eventually required removal of the prosthetic graft and below-knee amputation. Early groin reexploration and direct ligature of ruptured lymphatics was performed in the remaining five patients. Hospitalization was shortened and wound infection prevented in all patients in this group. We recommend prompt operative closure as the preferred approach in the management of lymph fistula following vascular reconstruction, especially when synthetic graft material is present.

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

A comparison of different regiments 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 microM and 5.3 microM, 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 microM. Among the aerosol groups, group A-40 approached steady state plasma R levels (8-10 microM) more quickly than group A-60.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Urinary tract infections.

Urinary tract infections (UTIs) are still the precipitating cause for 7 million patient visits per year with total costs exceeding one billion dollars. Diagnostic modalities have become more "friendly" for the smaller laboratory with "dip stick" culture tests providing a rapid method of isolation of pathogens. In many cases, empiric therapy is more cost effective than culture in uncomplicated UTIs in women. The etiologic organisms implicated in UTIs have not changed dramatically over the past two decades, with E. coli still accounting for the majority of cases. Antibiotic susceptibility patterns have changed dramatically, with ampicillin losing utility die to the emergence of resistance. Quinolones, which have been exceedingly active against gram-negative enteric pathogens, are no longer universally active and more pathogenic organisms, such as pseudomonas, may be resistant. The emergence of other highly resistant organisms, such as Enterococcus faecium, must be watched for.

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.

Impaired bacterial killing in early obstructive jaundice.

Sprague-Dawley rats were challenged with intraperitoneal injection of 10(7) Streptococcus pneumoniae 10 days after common duct ligation (BDL) or sham celiotomy (SC). Quantitative bacterial cultures were performed on liver, spleen, lung, kidney, and heart blood samples obtained 4 hours after injection. All 13 (100%) BDL animals had positive heart blood cultures, but only 6 of 12 (50%) SC animals remained bacteremic (p < 0.05). Significantly more viable organisms were recovered from lung, liver, spleen, and kidney of BDL animals compared with SC controls. BDL impaired the host's ability to kill this encapsulated gram-positive organism. Viable bacteria remained in all organs studied, which was associated with continuing bacteremia.

Increased ion transport in cultured nasal polyp epithelial cells.

OBJECTIVE: To measure transepithelial bioelectric properties of cultured human nasal polyp and turbinate epithelial cells to test the hypothesis that nasal polyps have increased rates of ion transport. DESIGN: Cohort study. SETTING: Private referral center. PATIENTS: Individuals undergoing surgery for symptomatic nasal obstruction due to polyps caused by cystic fibrosis, nonatopic rhinosinusitis, or allergic rhinosinusitis. METHODS: Epithelial cells were removed from separated polyp and turbinate samples by protease disaggregation and cultured on permeable collagen matrix supports. Transepithelial potential difference and resistance were measured daily. At the time of maximal transepithelial potential difference, the cultures were mounted in modified Ussing chambers and exposed to a sodium-positive channel blocker (amiloride hydrochloride) and to selected chloride-negative channel agonists (isoproterenol bitartrate, adenosine triphosphate). OUTCOME MEASURES: Maximal transepithelial potential difference, resistance, and equivalent short-circuit current. Bioelectric responses to amiloride, isoproterenol, and adenosine triphosphate. RESULTS: Polyp cultures had higher transepithelial potential difference and equivalent short-circuit current than turbinate cultures. The mediator responses were greater for polyp than for turbinate cultures. CONCLUSIONS: Polyp epithelia have increased Na+ absorption and Cl- permeability relative to turbinate epithelia. These results are consistent with the hypothesis that increased epithelial fluid absorption contributes to the development of nasal polyps.

Colon interposition versus esophagogastrostomy for esophageal carcinoma.

Thirty-eight patients underwent either a colon interposition (18 patients) or an esophagogastrostomy (20 patients) for cancer of the distal two-thirds of the esophagus. Both procedures had essentially the same 30-day mortality (22% versus 20%), a similar major complication rate (78% versus 75%), and recurrent dysphagia rate (17% versus 15%). The lowest complication rate was seen in the colon interposition for cure (33%), as compared to esophagogastrostomy for cure (70%). The longest average survival time (14.6 months) was seen after a colon interposition for cure, with 33 per cent of patients alive at two years, compared to 12.4 months average survival and 30 per cent alive at two year seen in the esophagogastrostomy for cure group. There were no five-year survivals. Preoperative radiation appeared to have a beneficial effect regardless of tumor cell type or operative procedure. Surgical management of esophageal cancer appears to be palliative in most instances, regardless of operation performed.

Infectivity of vascular sutures.

Bacterial adherence to vascular sutures was evaluated in vitro using radioactively labeled Staphylococcus aureus. The following suture materials were tested: polypropylene, silicone-treated braided polyester, and Teflon-treated braided polyester. Significantly fewer bacteria adhered to the monofilament polypropylene than either of the braided polyester sutures. There was no significant difference between silicone-treated and Teflon-treated polyester from the standpoint of bacterial adherence. Vascular sutures were evaluated in vivo using a mouse wound model. Sutures were tested with and without knots. When tested without knots, fewer bacteria were recovered from wounds containing polypropylene suture compared to either of the braided materials, although this apparent advantage did not prove to be statistically significant. When studied with knots, the differences among types of suture were much less marked and, again, not significant. The purported contribution of the monofilament structure of a suture to its infection resistance may have been overstated.

Reducing the cost of surgical prophylaxis.

A four-part program was implemented in order to control the rising cost of prophylactic antibiotics: limiting the number of cephalosporins on formulary; prohibiting the use of third- and most second-generation cephalosporins for prophylaxis; using a special order form to designate use as empiric, therapeutic, or prophylactic; and mandatory discontinuance of prophylactic antibiotics after 24 hours. The total cost for administration of prophylactic antibiotics was reduced from an average of $37.35 per case for the six months preceding the start of these restrictive policies to an average of $21.99 per case during the next twelve months. Class I and class II wound-infection rates were 2.0 per cent and 4.9 per cent, respectively, prior to the adoption of the new antibiotic practices. Comparable infection rates were 1.8 per cent and 2.1 per cent, respectively, after this program was initiated. The rising cost of antibiotic prophylaxis can be reduced without adversely affecting wound-infection rates.

The role of autonomic nervous system and inflammatory mediators in nasal hyperreactivity: a review.

The last decade has seen a marked increase in the number of otolaryngologists-head and neck surgeons who have been trained to perform rhinologic surgery. This includes both rhinoseptoplasty and endoscopic sinus surgery. A better understanding of the pathophysiology of rhinitis and sinusitis has also kept pace with this rapid expansion of surgical intervention. For example, significant advances have taken place in our knowledge of the local immune system in the nose, particularly in regard to mucosal and submucosal mast cells and the development of protective antibodies in the nasal mucosa against viral and bacterial infections. We have far more understanding of the complex innervation of the blood vessels and glands in the nasal mucosa and their receptors, and, most recently, a tremendous increase of scientific data has accumulated on the effect of neuropeptides on the nasal mucous membrane. It is imperative that rhinologic surgeons have an understanding and appreciation of the complex patterns of sensory and autonomic innervation of the nose to better evaluate the medical, allergic, and surgical treatment of acute and chronic rhinitis and sinusitis. This discussion will focus on recent advances in our understanding of the biochemical substances that are released by both the autonomic nervous system and the sensory nervous system in the nasal mucosa. The effect of these mediators on both vascular smooth muscle and the seromucinous glands of the nose will be considered. Finally, the dynamic interaction between the inflammatory mediators released by sensory nerves so-called tachykinins-- and the immune system and mast cell degranulation will be considered.

Role of allergy in eustachian tube blockage and otitis media with effusion: a review.

Recent studies continue to support a role for allergy in the pathogenesis of otitis media with effusion. Although a variety of mechanisms have been proposed to relate these two disease conditions causally, none has been completely validated by experimental or clinical studies. This review suggests that the observed relationship between allergy and otitis media with effusion is caused by mediators of inflammation and cytokines and colony-stimulating factors released by mucosal mast cells and other inflammatory and epithelial cells in the nose and nasopharynx. These mediators produce blockage of the eustachian tube through a number of mechanisms, which may include local injury or vascular- or neural-mediated changes in the eustachian tube opening pressure and in middle ear perfusion. It is likely that the nasal allergic response in patients predisposes to eustachian tube blockage and, if prolonged, causes changes in gas absorption in the middle ear space. This gas exchange primarily involves nitrogen absorption, which may take several days to develop. This persistent underpressure will then lead to middle ear effusion. Irrespective of the theoretical mechanism, the relationship between allergy and otitis media with effusion will remain controversial until well-controlled clinical studies are conducted documenting that in select populations antiallergy therapy is efficacious in preventing or limiting the duration of otitis media with effusion.

The role of IgE-mediated hypersensitivity in the development of otitis media with effusion: a review.

Otitis media with effusion is the most common cause of hearing loss in children today. This report examines the role of immunoglobulin E-mediated hypersensitivity in the development of otitis media with effusion. It is emphasized that immunoglobulin E-mediated hypersensitivity, or allergy, represents only one variable in a very complex disease entity. Bacterial infection, viral infection, and mucociliary clearance are important variables that must be considered and may be effected by the allergic response. On the basis of the world literature and laboratory investigations at the Children's Hospital of Buffalo, it is concluded that otitis media is associated with allergy in 35% to 40% of cases. Furthermore, the middle ear mucosa itself is rarely a target organ for allergy. Release of biologic mediators of inflammation from basophils and mast cells occurs in the nasal mucosa and nasopharyngeal mucosa. These mediators most likely produce eustachian tube edema and inflammation. Over a long period this chronic inflammatory response, along with viral or bacterial infection, produces middle ear effusion.

Defective immunoregulation in children with chronic otitis media with effusion.

Otitis media and middle ear effusions (MEE) are most common clinical problems in early childhood, for which an estimated one million tympanostomies are performed each year in the United States. Although many factors have been associated with MEE (age, sex, genetics, otitis media, socioeconomic status, feeding style, atopy or hypersensitivity, certain bacteria and viruses), a defective immunoregulatory mechanism in the host may also contribute to the pathogenesis. During the past 2 years, we have evaluated immune function in 90 randomly selected children who underwent repeated tympanostomy for persistent MEE. The T-cell subset ratio (OKT-4/OKT-8) was reduced (below 1.25) in 16%. In 33 children, generation of T-cell growth factor (IL-2) by peripheral blood lymphocytes (PBL) was evaluated and found to be decreased in 11. The mitogenic response of PBL to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) stimulation was abnormal in almost half of the cases. Imbalance of T-cell subsets and decreased production of IL-2 indicate defective immunoregulatory function in some of these children, which may play a role in the pathogenesis of persistent MEE.