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Biomedical subjects

D M Bamberger

Publications and source records attributed to D M Bamberger.

32 records · Page 2Linked to original sources

Efficacies of various antimicrobial agents in treatment of Staphylococcus aureus abscesses and correlation with in vitro tests of antimicrobial activity and neutrophil killing.

A rabbit perforated-capsule model was utilized to study antimicrobial efficacy in treating 2-week-old Staphylococcus aureus abscesses. Animals received either ciprofloxacin (30 mg/kg), cefazolin (100 mg/kg), or ciprofloxacin (30 mg/kg) plus rifampin (20 mg/kg) every 8 h for 8 days or no antibiotic. Antibiotic levels within the abscess exceeded the MIC for the test organism. At the end of treatment, ciprofloxacin was no more effective than the control, animals receiving cefazolin had a mean log10 fall of 2.41 CFU/ml, and animals receiving ciprofloxacin plus rifampin had a mean log10 reduction of 5.06 CFU/ml (P = less than 0.01). Six days after completion of therapy, all abscesses in animals receiving ciprofloxacin plus rifampin were culture negative. Surviving organisms in animals receiving ciprofloxacin or rifampin did not develop resistance to the treatment antibiotics. In vitro time-kill curves performed with logarithmic- and stationary-phase organisms in broth, serum, and abscess fluid supernatants did not correlate with the in vivo results. Neutrophil killing studies of S. aureus pretreated with antibiotics revealed greater killing of organisms pretreated with ciprofloxacin plus rifampin than of those pretreated with cefazolin or ciprofloxacin alone. In conclusion, ciprofloxacin plus rifampin was effective therapy in this staphylococcal abscess model, compared with the moderate efficacy of cefazolin and no effect observed with ciprofloxacin alone. Enhanced neutrophil killing of S. aureus pretreated with antibiotics may be an important mechanism by which bacteria are killed in suppurative infections.

Abscess↗

Antimicrobial treatment of sinusitis.

Sinusitis is a common disease. Most cases of acute sinusitis involve the maxillary sinus and occur after viral infections of the upper respiratory tract. The usual pathogens are Streptococcus pneumoniae and Haemophilus influenzae. Moraxella (Branhamella) catarrhalis is also an important pathogen in children. Anaerobic infections are more common in chronic sinusitis. Fungi are frequently observed in granulocytopenic cancer patients but also can occur in apparently normal hosts. Many strains of H influenzae and M catarrhalis observed in patients with sinusitis produce beta-lactamases. Many antimicrobial regimens have proven successful in the treatment of sinusitis, including ampicillin, amoxicillin, trimethoprim-sulfamethoxazole, the tetracyclines, and cefuroxime axetil, but only the latter three drugs are active against most beta-lactamase-producing strains. Nosocomial sinusitis usually occurs in intensive care unit settings and is frequently associated with nasopharyngeal instrumentation. The pathogens observed in nosocomial sinusitis are gram-negative bacilli or staphylococci and frequently require therapy with broad-spectrum penicillins or cephalosporins, an aminoglycoside, or vancomycin.

Anti-Bacterial Agents↗

Bactericidal capacity of neutrophils in rabbits with experimental acute and chronic abscesses.

Bacteria persist within abscesses despite the presence of neutrophils, and patients with abscesses have high rates of subsequent infections. A model was developed to study neutrophil function in rabbits with Staphylococcus aureus abscesses. Blood neutrophils from rabbits with 2-week-old (chronic) abscesses had diminished bactericidal capacity and decreased superoxide production compared with rabbits with 24-h (acute) abscesses. Rabbits with chronic abscesses did not produce serum opsonic factors that enhanced bacterial killing. A bactericidal assay performed with chronic abscess fluid in the suspending medium revealed inhibition of neutrophil killing. The inhibition could be replicated with a neutrophil lysate but not by an S. aureus supernatant. Rabbits with chronic abscesses have diminished blood neutrophil bactericidal capacity and superoxide formation, and the abscess fluid milieu is inhibitory to neutrophil function.

Abscess↗

Haemophilus influenzae meningitis in an adult with initially normal cerebrospinal fluid.

We have described an adult patient with signs and symptoms of bacterial meningitis who had an initially unremarkable cerebrospinal fluid examination, but then had development of fulminant meningitis over the next 48 hours. Bacterial meningitis with normal CSF values has been previously reported in children, immunocompromised hosts, and alcoholics, and in patients with fulminant infections due to Neisseria meningitidis. We recommend that all patients with signs and symptoms compatible with bacterial meningitis and with normal results of CSF examination have close follow-up clinically over the next 48 hours with consideration of repeating the lumbar puncture.

Adult↗

Spontaneous clostridial myonecrosis in a man with drug-induced agranulocytosis.

A middle-aged man had spontaneous clostridial myonecrosis during a period of neutropenia caused by drug-induced agranulocytosis. This complication in the absence of any prior cytotoxic chemotherapy or any evidence of an ileocecal neoplasm argues for the central role of neutropenia in the development of this rare syndrome. Survival of the patient was dependent upon prompt, aggressive medical and surgical management and the spontaneous recovery of the neutrophil count.

Agranulocytosis↗

Neutrophil chemotaxis and adherence in vitro and localization in vivo in rabbits with Staphylococcus aureus abscesses.

Decreased neutrophil (PMN) function may contribute to an altered host defense system in hosts with bacterial abscesses but has not been well correlated to in vivo outcome. We have found that blood PMNs from rabbits with chronic (2-week) experimental Staphylococcus aureus abscesses have decreased chemotaxis in response to an S. aureus supernatant (370 +/- 130 microns migration vs 570 +/- 180 microns, p less than 0.05) and decreased adherence (11.5% +/- 13.2% vs 32.9% +/- 18.6%, p less than 0.005) compared with PMNs from animals with acute (24-hour) abscesses. No differences were found in chemokinesis, random migration, and chemotaxis in response to zymosan-activated serum. No plasma inhibitors of PMN chemotaxis or inhibitors of chemotaxins were found. Although animals with chronic abscesses had higher levels of circulating chemotaxins, in both groups of animals abscess chemotaxin levels were greater than the plasma chemotaxin level. Animals with a concomitant chronic abscess had less PMN influx into an acute abscess but also less bacterial growth within the abscess than animals without a concomitant chronic abscess. We conclude that rabbits with chronic staphylococcal abscesses have decreased chemotaxis and adherence measured in vitro and decreased PMN localization in vivo. In this model, these functions were not associated with increased bacterial proliferation in vivo.

Abscess↗

Diagnosis of nosocomial pneumonia.

Nosocomial pneumonia occurs in 0.6% of hospitalized patients. The usual causative agents are gram-negative bacilli, Staphylococcus aureus, Streptococcus pneumoniae, and anaerobic bacteria. In immunocompromised hosts, the differential diagnosis also includes fungi, mycobacteria, viruses, Nocardia, and Pneumocystis carinii. Important risk factors for the development of nosocomial pneumonia include prolonged mechanical ventilation, thoracic or upper abdominal surgery, altered mental status, underlying immunosuppression, chronic obstructive pulmonary disease, and the use of antacids or histamine type 2 blockers. Colonization of the oropharynx and tracheal secretions with gram-negative aerobic bacteria is common in hospitalized patients with or without pneumonia. The diagnosis of nosocomial pneumonia is usually based on the clinical features of dyspnea, cough, fever, purulent sputum production, new pulmonary infiltrates, hypoxemia, and leukocytosis. However, the clinician must recognize that the presence of these features is neither sensitive nor specific in the diagnosis of nosocomial pneumonia. Microbiologic diagnosis is also difficult because blood cultures are usually negative, and cultures of tracheal secretions, although usually sensitive, are not specific. Invasive procedures may prove useful, but most have yet to be studied in large groups of patients with nosocomial pneumonia.

Bacterial Infections↗

Osteomyelitis in the feet of diabetic patients. Long-term results, prognostic factors, and the role of antimicrobial and surgical therapy.

Fifty-one diabetic patients with osteomyelitis of the foot were studied to determine potential prognostic factors and the role of antimicrobial therapy. Most of the patients were elderly, with diminished pulses, a sensory neuropathy, and a polymicrobial infection. Twenty-seven patients had a good outcome, defined as clinical resolution at the time of the last follow-up examination, without the need for amputation. The mean duration of follow-up for these patients was 19 months. Fifteen patients had a below-knee amputation, and nine had a toe amputation. The absence of necrosis and/or gangrene, the presence of swelling, and the use of antimicrobial therapy active against the isolated pathogens for at least four weeks intravenously, or combined intravenously and orally for 10 weeks, predicted a good outcome. Diabetic foot osteomyelitis, in the absence of extensive necrosis or gangrene, usually responds to antimicrobial therapy without the need for an ablative surgical procedure.

Amputation, Surgical↗

Treatment and long-term follow-up of foot infections in patients with diabetes or ischemia: a randomized, prospective, double-blind comparison of cefoxitin and ceftizoxime.

The efficacy and safety of ceftizoxime and cefoxitin were compared in a randomized, double-blind study of therapy for lower extremity infections in patients with diabetes mellitus or peripheral vascular disease. Overall clinical responses were satisfactory in 82% (23/28) of patients treated with ceftizoxime and in 68% (17/25) of patients treated with cefoxitin. The difference was not statistically significant. Ceftizoxime had superior in vitro activity against Enterobacteriaceae, especially Enterobacter cloacae, whereas cefoxitin had better activity against the Bacteroides fragilis group. Relapses of infection were common in both groups during long-term follow-up; only about one third of patients in either group maintained satisfactory outcomes after one year. More than half of the patients in both groups responded to one or more courses of medical therapy and avoided major amputations for one year following entry into the study.

Aged↗

Neutrophil localization in acute and chronic experimental abscesses.

Abdominal abscesses are associated with a high mortality, and usually require surgical drainage for cure. A potential mechanism explaining the inability of the host to clear this infection may be in part a result of the inability of the neutrophil to localize at the site of an established infection. To study this question, either acute (4 hours old) or chronic (2 weeks old) abscesses caused by Staphylococcus aureus were created in perforated capsules implanted in the peritoneal cavity of rabbits. Homologous neutrophils were obtained from donor rabbits 4 hours after peritoneal glycogen stimulation and labeled with indium 111 oxine. Only 0.71% of injected 111In-labeled neutrophils localized in the chronic abscesses, compared with 1.77% in acute abscesses (P less than or equal to 0.01). Animals with chronic infections had a lower intravascular recovery of injected neutrophils (P less than 0.002). Failure of neutrophil localization was not associated with less chemotactic activity within the abscess, as measured by a chemotaxis-under-agarose assay, or caused by a barrier surrounding the abscess as detected by radionuclide imaging. Only 0.07% of injected neutrophils localized into acute abdominal abscesses in animals with a concomitant chronic subcutaneous abscess. These chronically infected animals also demonstrated a low peak intravascular recovery of injected neutrophils when compared with animals with only an acute infection (P less than 0.002). These data reveal that neutrophils localize to abscesses poorly in animals with chronic infections. The mechanism is possibly related to a systemic factor(s) associated with a lower intravascular recovery of injected neutrophils in chronically infected animals.

Abscess↗

Ciprofloxacin, azlocillin, ceftizoxime and amikacin alone and in combination against gram-negative bacilli in an infected chamber model.

Ciprofloxacin, azlocillin, ceftizoxime, and amikacin were studied alone and in combination against six Enterobacteriaceae and six strains of Pseudomonas aeruginosa in an infected chamber model in rabbits simulating a closed space infection. In-vivo results were compared with in-vitro tests of inhibition, killing and synergy. Ciprofloxacin was the most effective single agent, with efficacy against five of the six Enterobacteriaceae when used in low doses, and two of the six pseudomonads when used in high doses. The development of in-vitro resistance to ciprofloxacin was observed during therapy in strains which failed to be eradicated. Ciprofloxacin and azlocillin together was the most effective regimen, with efficacy against eleven of the twelve strains. Synergy, as determined by chequerboard testing, did not correlate with in-vivo outcome. Unlike mezlocillin, azlocillin, ceftizoxime or amikacin, MIC testing of ciprofloxacin was predictive of in-vivo success.

Amikacin↗

Relation between in vivo abscess localization and in vitro migration and adherence of neutrophils.

Rabbit peripheral blood and glycogen-stimulated peritoneal neutrophils were labeled with [111In]indium oxine and transfused intravenously into recipient rabbits with experimental abdominal abscesses due to Staphylococcus aureus. Peritoneal neutrophils harvested 4 hr after glycogen infusion localized within the abscesses to a greater extent than did peripheral blood neutrophils (P less than .002). In an in vitro chemotaxis under-agarose assay, peripheral blood neutrophils had greater random migration (P less than .002) and directed migration (P less than .01) than did peritoneal cells. In an in vitro glass slide adherence assay, peritoneal neutrophils were more adherent than were blood neutrophils (P less than .05). The discrepancy between in vivo and in vitro findings may be due to the increased adherence of peritoneal neutrophils. Glycogen-stimulated peritoneal neutrophils have been exposed in vivo to C5a, which is known to decrease migration and increase adherence in vitro of polymorphonuclear neutrophils; consequently, in vivo exposure of neutrophils to C5a may mean in vitro migration data may be misleading in predicting results in vivo.

Abscess↗