Netilmicin in the treatment of infections in patients with cancer.

Ninety-two patients with cancer with 100 infectious episodes were treated with netilmicin sulfate, a new aminoglycoside. Netilmicin was administered intravenously, either intermittently or by continuous infusion. The overall cure rate was 60%. Gram-negative bacilli were the most common causative organisms and the response rate for these infections was 32/53 (60%). The most common pathogens were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Pneumonia, urinary tract infection, and septicemia were the most common types of infection treated and the response rates were 23/47 (49%), 19/21 (90%), and 9/17 (53%), respectively. Nephrotoxicity occurred in ten patients (6%) who had normal renal function initially. Netilmicin is an effective aminoglycoside with a spectrum of antibacterial activity similar to that of gentamicin sulfate and it appears to be less nephrotoxic.     

A prospective randomised comparison of cefotaxime vs. netilmicin vs. cefotaxime plus netilmicin in the treatment of hospitalised patients with serious sepsis

93 patients were enrolled into a prospective randomised study to determine the efficacy and safety of netilmicin, cefotaxime or their combination in the treatment of sepsis caused by susceptible strains of Enterobacteriaceae or staphylococci. 83 patients were evaluable for safety, 74 for clinical efficacy and 63 for microbiological response including 36 patients (57%) with positive blood cultures. There were significantly more clinical failures with cefotaxime than with netilmicin even when urinary tract sepsis was excluded. Microbiological failures occurred more frequently in the cefotaxime arm and were associated with Klebsiella and Enterobacter spp. Four cefotaxime failures were subsequently successfully treated with netilmicin. More mixed infections were however enrolled by chance into the cefotaxime arm. The statistical difference between netilmicin and cefotaxime is not significant if mixed infections are excluded. There was no difference in efficacy between the netilmicin and combination groups although superinfection was seen in the latter group. The incidence of nephrotoxicity was greater in the netilmicin group but not significantly so. Only one minor case of ototoxicity was detected in the 41 patients receiving netilmicin who had serial audiograms. The results suggest that netilmicin is a more effective agent than cefotaxime for treating life-threatening infections with susceptible Enterobacteriaceae or staphylococci particularly with infections in non-urinary tract sites. If dosage of netilmicin is closely monitored by measuring serum concentrations, toxicity is minimal.     

Single-dose treatment with netilmicin for different clinical forms of urinary tract infections

Summary A group of 44 patients with various clinical forms of urinary tract infections received a single dose of 300 mg netilmicin i.m. The treatment was efficacious in all patients with infections which were negative in the antibody-coated bacteria test and not complicated by anatomic and/or functional abnormalities of the kidneys and urinary tract. After three weeks the recurrence rate was only 19%. Single-dose treatment also proved very effective against urinary tract infections in renal transplant patients whose infection is almost always located in the lower urinary tract. In contrast, the short-term results of treatment were much poorer in complicated infections and particularly in urinary tract infections which were positive in the antibody-coated bacteria test; here, the recurrence rate was 67%.

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Therapie verschiedener klinischer Formen von Harnwegsinfektionen mit einer Einzeldosis von Netilmicin

Zusammenfassung 44 Patienten mit verschiedenen klinischen Formen von Harnwegsinfektionen wurden mit einer Einzeldosis von 300 mg Netilmicin i.m. behandelt. Die Therapie erwies sich als sehr wirksam gegen Infektionen bei allen Patienten mit negativen Ergebnissen im Test auf antikörperbeladene Bakterien und ohne anatomische und/oder funktionelle Nieren- und Harnwegsanomalien. Nach drei Wochen rezidivierte die Infektion nur bei 19% der Patienten. Nierentrans-plantierte patienten, bei denen die Infektion fast immer in den unteren Harnwegen lokalisiert ist, sprachen ebenfalls sehr gut auf die Behandlung mit einer Einmaldosis Netilmicin an. Die kurzfristigen Behandlungsergebnisse waren dagegen bei komplizierten Infektionen, insbesondere bei Harnwegsinfektionen mit positivem Test auf antikörperbeladene Bakterien, sehr viel schlechter; die Rezidivrate betrug 67%.

     

奈替米星的临床研究

目的研究来替米星每日1次投药法治疗下呼吸道感染的临床效果、药代动力学、抗生素后效应和药物毒性。方法48例患者分为三组：（1）单一组14例,使用奈替米星,每天总量为6mg·kg-1·h-1;（2）合用组16例,使用头孢唑啉每12小时1次投药3g,奈替米星每天200mg;（3）对照组18例,使用头胞唑啉每12小时投药3g,与阿米卡星每天200mg联合使用,分别观察临床症状、实验室检查及临床疗效;应用荧光偏振分析仪（TDX）药物浓度自动分析仪研究其药代动力学;应用AVANTAGE生物分析仪研究奈替米星抗生素后效应,观察了奈替米星的肾、耳毒性。结果每日1次单用奈替米星组疗效较头抱叹批及阿米卡星组好。平均血药浓度为27．23mg／L谷浓度为0．23mg／L,半数药物消除相时间为5．095小时,药时曲线下面积为70μg·h-1·ml-1。奈替米皇0．5、1及4倍最低抑菌浓度（MIC）对4种细菌均显示不同程度的抗生素后效应。本组研究未发现耳、肾毒性。结论奈替米星每日1次投药法有较高血清浓度,较大药时曲线下面积,作为浓度依赖性杀菌药,此药临床效果较好,而且其抗生素后效应时间较长。     

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients

Summary We assessed the efficacy of a piperacillin (3×4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.

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Piperacillin in Kombination mit Netilmicin zur Therapie bei granulozytopenischen Patienten mit Fieber

Zusammenfassung Die Wirksamkeit von Piperacillin (3×4 g/Tag) in Kombination mit Netilmicin (5 mg/kg/Tag) in der Therapie fieberhafter Infektionen bei neutropenischen Patienten wurde geprüft. Die Studie wurde mit 203 Patienten über einen Zeitraum von 30 Monaten geführt. Knochenmarkstransplantatempfänger wurden in die Studie nicht aufgenommen. In 101 Fällen (50%) konnte ein Erreger indentifiziert werden. In 33 Fällen wurden Pilze, Viren oder Parasiten nachgewiesen, in 68 Fällen, meist Septikämien, bakterielle Erreger. 129 der insgesamt 169 auswertbaren Patienten (76%), bei denen eine dokumentierte bakterielle Infektion oder Fieber unbekannter Ursache vorlag, sprachen auf die Behandlung mit Piperacillin plus Netilmicin an. Alle Infektionen durch grampositive Bakterien, die auf die Primärtherapie nicht angesprochen hatten, wurden durch eine Zusatztherapie mit Vancomycin geheilt. In dieser großen, prospektiven Studie an einem Zentrum erwies sich die Kombination von Piperacillin und Netilmicin als sehr wirksam. Bei Patienten unserer Klinik erschien die primäre Zusatztherapie mit Vancomycin bei neutropenischen Patienten nicht erforderlich. Wenn jedoch eine Staphylokokkeninfektion nachgewiesen wird oder der Verdacht darauf besteht und die empirische Therapie sich als unzureichend wirksam erwiesen hat, muß frühzeitig mit einer Vancomycin-Zusatztherapie begonnen werden.

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Supported by Lederle-Cyanamid France.     

Inactivation of netilmicin by carbenicillin

Summary Netilmicin was added to human serum and stored at various temperatures and carbenicillin concentrations prior to bioassay. Inactivation of netilmicin increased with temperature and carbenicillin concentration. The order of inactivation of aminoglycosides was: tobramycin > gentamicin, netilmicin > amikacin.

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Inaktivierung von Netilmicin durch Carbenicillin

Zusammenfassung Netilmicin wurde Humanserum zugesetzt und vor der biologischen Auswertung bei verschiedenen Temperaturen und Carbenicillinkonzentrationen gelagert. Die Inaktivierung von Netilmicin nahm mit steigender Temperatur und Carbenicillinkonzentration zu. Die Inaktivierung von Aminoglykosiden ergab die Reihenfolge: Tobramycin > Gentamycin > Netilmicin > Amikacin.

     

Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone

PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.     

COMPARISON OF NETILMICIN WITH CEFOPERAZONE FOR THE TREATMENT OF SEVERE OR COMPLICATED URINARY TRACT INFECTIONS

Abstract: :A randomised trial was undertaken to compare the efficacy and safety of netilmicin and cefoperazone for the treatment of severe or complicated urinary tract infections. Thirty-two patients completed the study. Fifteen of 16 patients treated with netilmicin and nine of 16 treated with cefoperazone were cured. This difference was statistically significant (p = 0.037). No serious side effects or toxicity occurred with either drug, although five patients developed diarrhea after treatment with cefoperazone. (Aust NZ J Med 1985; 15: 22–26.)     

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.     

Bactericidal activity of antibiotics alone and in combination against Enterococcus faecalis in a pharmacodynamic model.

We evaluated the bactericidal kinetics of teicoplanin, mezlocillin, netilmicin, and ciprofloxacin alone and in dual combinations against strains of Enterococcus faecalis susceptible or resistant to ampicillin in a pharmacodynamic model reproducing in bacterial culture in active human plasma or Mueller-Hinton broth the serum kinetics of these antibiotics in humans. Killing was not different in cultures grown in plasma and those grown in broth. Antibiotics used alone had no or low bactericidal activity except for high-dose ciprofloxacin (600 mg intravenously [iv] twice daily or 750 mg orally twice daily), which achieved a 3- to 4-log reduction in colony-forming units (cfu). Netilmicin was equally active at 6 mg/kg once a day or 2 mg/kg three times daily in all combinations. No major increase in bactericidal activity was detected in any combination that included mezlocillin. Maximal synergistic killing was observed for the combination of teicoplanin plus netilmicin (both at three-times daily and once-daily dosing), which sterilized the bacterial cultures (initial inoculum, 10(6) cfu/mL). Combinations of ciprofloxacin at 600 mg iv twice daily and 750 mg orally twice daily plus either teicoplanin or netilmicin were less synergistic but equally effective in total killing as a result of the high bactericidal activity of ciprofloxacin alone.     

A randomized clinical trial of ceftriaxone and teicoplanin versus ceftazidime and teicoplanin as antibiotic therapy in febrile neutropenic cancer patients and bone marrow transplant recipients

Summary A prospective, randomized clinical trial comparing combination therapy with ceftriaxone and teicoplanin versus ceftazidime and teicoplanin in the treatment of febrile episodes in neutropenic cancer patients and bone marrow transplant recipients was performed. One hundred and two patients were randomized, but two patients were considered unevaluable for efficacy, and three patients were withdrawn due to incorrect randomization. Of the remaining 97 patients, infection resolved without modification of therapy in 31/49 (63%) patients treated with ceftriaxone/teicoplanin versus 27/48 (56%) patients treated with ceftazidime/teicoplanin (P=0.48). Of all 97 patients treated therapy was modified in 18/49 (36%) with ceftriaxone/teicoplanin and 21/48 (43%) with ceftazidime/teicoplanin. Nineteen patients treated with ceftriaxone/teicoplanin received netilmicin and 21 patients treated with ceftazidime/teicoplanin also received netilmicin according to the study design (escalation therapy). When netilmicin was added infection resolved in 78% of patients treated with ceftriaxone/teicoplanin versus 84% of those treated with ceftazidime/teicoplanin. It was concluded that combination therapy with ceftriaxone/teicoplanin is an alternative to combination therapy with ceftazidime/teicoplanin, and has the advantage of once daily administration.

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Antibiotische Therapie der febrilen Neutropenie von Tumor- und Knochenmarktransplantationspatienten. Eine randomisierte Studie mit Ceftriaxon und Teicoplanin im Vergleich mit Ceftazidim und Teicoplanin

Zusammenfassung In einer prospektiven, randomisierten klinischen Studie wurde die Kombinationstherapie mit Ceftriaxon und Teicoplanin gegen die Kombinationspartner Ceftazidim und Teicoplanin bei neutropenischen Patienten oder Patienten nach Knochenmarktransplantation verglichen. Insgesamt wurden 101 Patienten in die Studie eingebracht, davon waren 97 Patienten auswertbar. In der Ceftriaxon/Teicoplanin-Gruppe waren 63% der Patienten geheilt, gegenüber 56% der Patienten in der Ceftazidim/Teicoplanin-Gruppe. Dieses Ergebnis war ohne Modifikation der Studien-Medikamente erreicht worden. Bei 18 von 49 Patienten in der Ceftriaxon/Teicoplanin-Gruppe und 21 von 48 Patienten in der Ceftazidim/Teicoplanin-Gruppe wurde von der Studienmedikation abgegangen und zusätzlich Netilmicin (Eskalationstherapie) gegeben. Durch die zusätzliche Gabe von Netilmicin waren 78% der Patienten in der Ceftriaxon/Teicoplanin-Gruppe und 84% in der Ceftazidim/Teicoplanin-Gruppe geheilt. Diese Daten deuten darauf hin, daß die Kombinationstherapie mit Ceftriaxon/Teicoplanin eine Alternative zur Kombinationstherapie mit Ceftazidim und Teicoplanin darstellt, zumal die Gabe von Ceftriaxon und Teicoplanin den Vorteil hat, daß diese Medikamente nur einmal pro Tag gegeben werden müssen.

     

Use of cefotaxime, a beta-lactamase stable cephalosporin, in the therapy of serious infections, including those due to multiresistant organisms

Cefotaxime is a cephalosporin active against most gram-positive and gram-negative organisms, including streptococci, Staphylococcus aureus, Enterobacteriaceae, Proteus, and many Pseudomonas and Bacteroides fragilis--all but the latter two are inhibited at concentrations below 0.5 micrograms/ml. We evaluated cefotaxime as the sole therapy for 32 infections in 31 patients. Infection sites included 18 bacteremias; pulmonary, urinary tract, deep tissue infections; and meningitis. Clinical cures were achieved in 88 percent and bacteriologic cures in 86 percent of the patients--including those with infections due to organisms resistant to cephalosporins, chloramphenicol, carbenicillin and aminoglycosides; and in two patients with meningitis due to multiresistant Klebsiella pneumoniae. Serum and cerebrospinal levels were readily maintained above the inhibitory levels of susceptible organisms. Adverse reactions were minimal. Cefotaxime was a safe, effective antibiotic in the treatment of infections due to susceptible organisms, including those resistant to other agents.     

Antihypertensive effects of captopril and saralasin in essential and renal hypertension

The antihypertensive effect of captopril and its mechanism of action were studied in patients with essential and renal hypertension. In mild essential hypertension (n = 12), during monotherapy with captopril (50 to 450 mg, 4 to 12 weeks) blood pressure was normalized in seven, improved in two and remained unchanged in three patients, plasma levels of active and acid-activatable inactive renin significantly increased and angiotensin II decreased, whereas no consistent changes in urinary kallikrein excretion occurred. In severe renal (n = 14) and essential (n = 9) hypertension, blood pressure was normalized in eight (seven with renal hypertension), improved in seven and unchanged in eight patients, when captopril (50 to 450 mg, 3 to 15 months) was added to the antihypertensive medication. In one patient with stenosis in a transplanted renal artery reversible renal failure occurred during captopril therapy possibly because of a steep initial decrease in blood pressure, although a toxic effect of the drug cannot be excluded. In another series of 12 renal and 8 essential hypertensive patients, a significant correlation between the acute effect of captopril (within 90 minutes) and saralasin on blood pressure was demonstrated (r = 0.71, p < 0.001). The change in blood pressure after either drug was significantly related to the initial plasma renin concentration.In conclusion, captopril sems to be an effective antihypertensive agent in essential and renal hypertension. Renal function should be monitored during captopril therapy. Our studies suggest that captopril decreases blood pressure by inhibiting the vasopressor action of the renin-angiotensin system.     

Sensitivity of gram-negative bacteria to six aminoglycoside antibiotics

Summary An in vitro study of the susceptibility of 201 newly isolated strains of gramnegative bacteria to six aminoglycoside antibiotics (kanamycin, amikacin, gentamicin, tobramycin, sisomicin and netilmicin) was performed by the twofold dilution method in fluid medium. Both the minimal inhibitory concentration and the minimal bacteridical concentration were determined. Overall, tobramycin seemed the most effective of the drugs studied. Netilmicin, the new derivative from sisomicin, compared favourably with the other drugs tested, but may, on theoretical grounds, offer the additional advantage of retained efficacy in the face of developing bacterial resistance. Not unexpectedly, amikacin appeared to be the most promising of the drugs studied in its action against Pseudomonas aeruginosa. Amikacin and netilmicin appeared to be the most effective of this group of antibiotics against Klebsiella species.

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Empfindlichkeit gramnegativer Bakterien gegenüber sechs Aminoglykosid-Antibiotika

Zusammenfassung Eine In-vitro-Studie über die Empfindlichkeit von 201 neu isolierten gramnegativen Bakterienstämmen gegenüber sechs Aminoglykosid-Antibiotika (Kanamycin, Amikacin, Gentamicin, Tobramycin, Sisomicin und Netilmicin) wurde mit Hilfe eines zweifachen Reihenverdünnungstests durchgeführt. Sowohl die minimale Hemmkonzentration als auch die minimale bakterizide Konzentration wurden bestimmt. Insgesamt erwies sich Tobramycin als das wirksamste der geprüften Medikamente. Im Vergleich zu den anderen untersuchten Medikamenten erzielte Netilmicin, das neue Derivat von Sisomicin, günstige Resultate. Außerdem hat dieses Medikament, rein theoretisch gesehen, den Vorteil einer stabileren Empfindlichkeit bei auftretender bakterieller Resistenz. Erwartungsgemäß erwies sich Amikacin als das zuverlässigste aller getesteten Medikamente gegen Pseudomonas aeruginosa. Als wirksamste Antibiotika gegen Klebsiella waren Amikacin und Netilmicin zu bezeichnen.

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Although this article does not deal directly with antibiotic treatment, the article was accepted for publication because resistance to the aminoglycoside antibiotics is attracting increasing attention in antibacterial therapy in hospitals. This subject will be dealt with again in a coming issue of INFECTION in an article byH. Knothe andV. Krcméry entitled Amikacin and Netilmicin Resistance in Pseudomonas aeruginosa.     

Long-term follow-up of incorporation of 15N from glycine into uric acid in gout

The incorporation of ¹⁵N-glycine into urinary uric acid was studied in three gouty patients, repeating a study carried out 13 to 27 years ago. The ¹⁵N incorporation attained a lower maximum and declined less rapidly in the repeat study in all three patients. The cumulative ¹⁵N incorporation into uric acid was reduced to one half of that determined previously. Similarly, urinary uric acid excretion was less, along with a lower uric acid nitrogen to total nitrogen ratio. The data indicate changes in the nature of the metabolic aberrations, which are apparently related to long-term drug therapy, changes in lifestyle, aging and associated medical complications.     

Short-course chemotherapy for tuberculosis with mainly twice-weekly isoniazid and rifampin. Community physicians' seven-year experience with mainly outpatients

The general medical community in the United States has been rather slow in adopting short-course bactericidal chemotherapy for tuberculosis despite the clear demonstration of the advantage by several carefully controlled clinical trials. Reported herein is experience between January 1976 and December 1982 in 1,028 patients with bacteriologically proved pulmonary tuberculosis treated for nine months with isoniazid (300 mg) and rifampin (600 mg) daily for one month followed by twice-weekly isoniazid (900 mg) and rifampin (600 mg) for the other eight months. They were treated by 45 local practitioners and supervised by public health nurses through 60 Arkansas Department of Health chest clinics in the state. Outpatient therapy was mostly self-administered in the routine treatment program. Overall success was achieved in 95 percent of the 751 patients who completed therapy; in 21 (2.8 percent), sputum cultures failed to convert to negative, and 15 (2.1 percent) have had relapse since therapy was stopped. Therapy could not be completed in 26.9 percent due to deaths, drug toxicities, relocation, refusal, etc. Of 21 bacteriologic failures, 18 patients developed isoniazid resistance and were treated with additional two bactericidal drugs. Most of the relapses (nine of 15) occurred within 12 months after chemotherapy was stopped. However, four relapses occurred quite late during follow-up. Only three of 15 patients with relapse showed isoniazid resistance. Side effects of the drugs were encountered in 10.3 percent, but major toxicities occurred in 3.2 percent (hepatitis in 2.6 percent, hematologic effects in 0.6 percent). Clinical surveillance for toxicity is preferred over routine and regular biochemical monitoring. Patient acceptance of the regimen was excellent, and compliance was good. Short-course chemotherapy is effective, with low drug toxicity, reduced cost of drugs, and ease of direct supervision when needed, and is acceptable to patients in routine treatment.     

Effect of propafenone in the Wolff-Parkinson-White syndrome: electrophysiologic findings and long-term follow-up

The electrophysiologic and long-term efficacy of propafenone, a relatively new antiarrhythmic agent, was assessed in 47 patients with accessory pathways. In 23 patients (group I), the electrophysiologic effects were assessed initially. In 19 patients in this group and in 24 additional patients (group II), long-term therapy with oral propafenone was initiated. The mean age of the patients was 38 years in group I and 41 years in group II. The duration of a history of tachycardia in both groups was 12 years (mean); 14 patients previously had had attacks of syncope. During the electrophysiologic study in group I, propafenone did not change the spontaneous sinus rate. Corrected sinus node recovery time as well as the AH interval, HV time, QRS duration and effective refractory periods of the atria and ventricles was significantly prolonged. The effective refractory period of the accessory pathway increased from 238 to 322 ms (p less than 0.02). The 1:1 conduction capacity of the accessory pathway decreased from 231 to 176 beats/min (mean; p less than 0.01). Complete block in the anterograde direction occurred in 6 patients. The shortest RR interval during atrial fibrillation increased from 232 to 303 ms (p less than 0.05). The retrograde refractory period of the accessory pathway was prolonged from 245 to 295 ms (p less than 0.01). Complete or 2:1 retrograde block during basic drive occurred in 3 patients and 1 patient, respectively. In 6 of 15 patients, propafenone made sustained supraventricular tachycardia (SVT) either no longer inducible or nonsustained. The cycle length of induced SVT increased from 324 to 395 ms (p less than 0.01). During long-term administration (follow-up duration 2 to 3 years), 17 of 43 patients did not report any episode of symptomatic tachycardia. In another 18 patients, tachycardia was rare, slower and self-terminating. In only 3 patients, the frequency and severity of attacks had not changed. One patient with dilated cardiomyopathy died suddenly. Side effects necessitating discontinuation of medication were observed in only 2 patients. The remaining side effects, if present, were tolerated, and dosage dependent. In conclusion, propafenone is an effective and well-tolerated antiarrhythmic agent in the long-term management of patients with the Wolff-Parkinson-White syndrome.     

Enterococcal bacteremia in a pediatric institution: a four-year review

We identified 77 cases of enterococcal bacteremia in 76 children hospitalized at a tertiary care pediatric institution from 1985 to 1989. To define the clinical characteristics of children with enterococcal bacteremia and to assess the bacteriologic features of the infecting isolates, we retrospectively reviewed the charts and reanalyzed the bacteriologic data for 50 cases. Eighty-two percent of cases of bacteremia were nosocomial, and 26% were polymicrobial. Ninety-two percent of patients had significant underlying medical problems and/or had undergone recent surgery. Associated sites of infection included endovascular sites (two cases), the skin (two), and the urinary tract (one). Forty-eight percent of the patients had received antibiotics within 7 days preceding enterococcal bacteremia. Crude mortality figures for patients receiving appropriate two-drug therapy, appropriate monotherapy, and either no therapy or inappropriate therapy were 7%, 20%, and 6.25%, respectively. Children with enterococcal bacteremia constitute a heterogeneous group, although the great majority of cases are acquired in the hospital by children with serious underlying disease. Studies delineating appropriate antibiotic treatment for varied situations are needed.     

A large outbreak of infections caused by a strain of staphylococcus aureus resistant to oxacillin and aminoglycosides

An extensive outbreak of nosocomial infections caused by oxacillinand aminoglycoside-resistant Staphylococcus aureus (OARSA) occurred over a 16 month period. A total of 349 isolates of OARSA were obtained from 174 patients. Colonization with OARSA was found in 92 patients. There were 120 infections in 82 patients; 50 were surgical wound infections, 13 were nonsurgical wound infections, six were pneumonias, 15 were urinary tract infections, 12 were intravenous site infections, and there were 19 episodes pf bacteremia (seven transient, 12 persistent). In patients with persistent bacteremia, the mortality rate was 33 percent. In patients treated for persistent bacteremia with vancomycin, the survival rate was 80 percent. Infections were highly associated with the surgical intensive care unit, and 90 percent of the isolates of OARSA tested had the same phage-type. Elderly patients with significant underlying disease, a history of previous surgery or of prior antimicrobial therapy appeared to be at increased risk for OARSA infections. OARSA were resistant to multiple antibiotics besides oxacillin, but all isolates were sensitive to vancomycin and rifampin. Three surgical intensive care unit nurses were found to be nasal carriers of OARSA, and one nurse had dermatitis of both hands colonized with OARSA. Following the removal of these nurses from the surgical intensive care unit and the institution of strict infection control measures, the number of OARSA infections and colonizations decreased to less than one per month. OARSA produces serious nosocomial disease, and epidemiologic intervention was effective in controlling this outbreak.     

Duration of treatment of urinary tract infections

This review was stimulated by the current interest in use of singledose therapy for uncomplicated “lower tract” infection in females and the potential benefit of long-term prophylaxis for patients with recurrent infections. Duration of therapy is only a tactic. It is dependent on understanding the natural history of urinary tract infections in relation to risk factors and the predictable response to treatment. Based on the pertinent literature, a series of elements are presented that define the current consensus concerning the definition, natural history and risk of renal damage from urinary tract infection. These are then considered in relation to the current diagnostic measures and procedures to localize infection. Single-dose therapy combined with bacteriologic monitoring appears to be a useful method to localize infection. Although it defines individuals who may require more prolonged treatment, it has not yet been shown to predict risk of renal damage or identify a subpopulation requiring further study. The major predictors of renal injury are anatomic and neurologic lesions that alter urine flow and host factors that decrease resistance to infection. These are currently better defined by individual patient characteristics and clinical observation than by localization studies. Long-term low-dose prophylaxis has been shown to be an effective means of management of highly recurrent episodes of infection. It does not, however, appear to prevent recurrences, after therapy has been discontinued, even after periods of prophylaxis as long as six months. Treatment should be based on reasonable expectancy of reduction in morbidity and/or renal damage.