Correlation between hearing loss and peritonitis frequency and administration of ototoxic intraperitoneal antibiotics in patients with CAPD.

AIM: Aminoglycosides have been used in the treatment of CAPD peritonitis despite their potential risk for ototoxicity. The ototoxicity risk of intraperitoneally administered aminoglycosides has been investigated by a number of studies. However, their results are somewhat conflicting. The aim of the present study was to examine the frequency of hearing loss and the correlation between the repeated doses of aminoglycosides and hearing loss in CAPD peritonitis therapy. METHODS: Hearing functions of the CAPD patients who had developed peritonitis and had been treated with various antibiotics including aminoglycosides were compared with those CAPD patients who had never developed peritonitis. Threshold values for hearing were determined through "pure tone audiometry" measurements. RESULTS: Hearing threshold levels of the patients with history of peritonitis were found to be significantly higher in both lower [pure tone averages - 1 (PTA-1)] and higher [pure tone averages - 2 (PTA-2)] frequencies, when compared to the ones with no history of peritonitis (p values were 0.001 and 0.007, respectively). CONCLUSION: The present study showed that intraperitoneal aminoglycoside administration in CAPD patients is associated with the development of hearing loss. The severity of hearing loss may range from mild hearing loss to profound deafness. A remarkable correlation exists between the severity of the hearing loss and the repeated and total aminoglycoside dose received.

Nephropathy associated with methicillin therapy. Prevalence and determinants in patients with staphylococcal bacteremia.

The nephropathy associated with methicillin sodium therapy is considered to be rare, but its prevalence is unknown. We reviewed the antibiotic therapy of 81 cases of Staphylococcus aureus bacteremia to establish the frequency and determinants of methicillin nephropathy in that disease. Fifty-two patients received methicillin; nine (17%) experienced the characteristic clinical signs previously associated with drug-induced acute interstitial nephritis. This nephropathy uniformly subsided after methicillin was withdrawn, and did not always include deterioration of renal function. Factors that correlated with methicillin nephropathy were endocarditis and prolonged treatment, but not intravenous drug abuse. There was only one adverse reaction among 29 patients treated with a cephalosporin. It was similar to the nephropathic reactions to methicillin. Thus, reversible renal abnormalities are prevalent during methicillin therapy, particularly among patients with staphylococcal infections such as endocarditis. When prolonged therapy with methicillin is required, the urinary sediment and renal excretory function should be monitored.

Antibiotic combination-associated nephrotoxicity in granulocytopenic patients with cancer.

Antibiotic combination-associated nephrotoxicity was reviewed in 491 granulocytopenic patients with cancer and fever. Nephrotoxicity was defined as a rise in the serum creatinine level of more than 0.4 mg/dL. The different aminoglycosides, when combined with ticarcillin disodium, were found to have an equivalent nephrotoxic potential and, for the purpose of analysis, were combined and termed "aminoglycoside plus ticarcillin" (Ags + ticarcillin). Groups treated with gentamicin or amikacin plus cephalothin sodium were combined and termed "aminoglycoside plus cephalothin" (Ags + cephalothin). The rate of nephrotoxicity was statistically less for the Ags + ticarcillin group, eight (3.1%) of 262 patients, than for the Ags + cephalothin group, 23 (18.3%) of 126 patients. Age greater than 50 years was a potentiating factor for the occurrence of nephrotoxicity in the Ags + cephalothin group. We have concluded that for granulocytopenic patients with cancer and fever, the antibiotic combination of the Ags + cephalothin should not be used as empiric antibiotic therapy.

Nephrotoxicity associated with cephalothin administration.

Variable degrees of acute renal failure developed in three patients receiving therapy with cephalothin sodium. The course and findings were consistent with acute tubular necrosis of the oliguric and nonoliguric types. One patient had protracted oliguria, a second experienced transient oliguria, and one had normal urine output. All had urinary sediment changes consistent with tubular necrosis, and the two oliguric patients had elevated urine sodium concentrations. No other causes for renal failure could be detected, and all recovered after discontinuation of cephalothin therapy, although peritoneal dialysis was required in one patient. These observations indicate that cephalothin is capable of inducing renal damage in man.

Nephrotoxicity of combined cephalothin-gentamicin regimen.

Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.

Grand rounds: autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AHA) may be either primary (ie, "idiopathic," one third of all patients) or secondary (ie, associated with underlying illness, two thirds of all patients). A positive Coombs antiglobulin test is the most important criterion for diagnosis of AHA, and characterization of RBC coating (as to whether it is by IgG alone, by IgG plus complement, or by complement alone) may be valuable in ruling out certain underlying illnesses as causative in selected patients. Many limitations to the antiglobulin test must be kept in mind. As routinely performed, a positive result requires greater than 500 molecules of IgG per RBC. Red blood cells from normal subjects have less than 35 molecules of IgG per RBC. Up to 2% to 5% of patients with AHA will have RBC coating in the 50 to 500 molecules per cell range and may therefore have "false"-negative antiglobulin tests. Apparent failures of strength of antiglobulin reactions to correlate with severity of in vivo RBC destruction may result from technical factors or may reflect intrinsic differences among autoantibodies (eg, IgG subclass, affinity). A likely mechanism of in vivo RBC destruction in AHA has been demonstrated in immune-mediated in vitro RBC "rosette" formation about macrophages and lymphocytes bearing specific receptors for subclasses of IgG and for subcomponents of complement. Increased avidity of macrophages for coated RBCs in response to such stimulus as infection may play an additional role. Treatment involves control of underlying disease and the judicious use of adrenal steroids, splenectomy, and immunosuppressive agents. Transfusions, while life-saving in life-threatening anemia, carry substantially increased risks in AHA patients. Their use should be strictly limited.

Comparative study of prophylactic antibiotics in cardiac surgery. Clindamycin versus cephalothin.

A randomized, prospective study of the relative effectiveness of clindamycin versus cephalothin was performed in 263 adult patients having cardiac surgery from September, 1977, to August, 1978. There were no statistically significant differences in frequency of postoperative infections in these two antibiotic groups. Wound infection developed in 6.5 percent of the cephalothin group and 3.2 percent of the clindamycin group. Urinary tract infection developed in 5.6 percent of the clindamycin group and 2.1 percent of the cephalothin group. Four bacteremic episodes occurred in the clindamycin-treated patients, and one episode of bacteremia occurred in a cephalothin-treated patient. No cases of endocarditis occurred during the study. Clindamycin deserved consideration as an alternative prophylactic agent to cephalothin for cardiac surgery.

Eosinophilic occlusive pulmonic panarteritis associated with long-term antibiotic therapy.

The administration of antibiotics through central catheters for short periods of time frequently is encountered clinically. This report is an in vivo experimental study of long-term bolus administration of antibiotics through a central catheter inserted in the external jugular vein. Approximately 30 calves, which weighed between 180 and 225 kg, had silicone-rubber catheters inserted for protracted periods of time. Various concentrations of either penicillin, cephalothin, or streptomycin were given intravenously in bolus doses. Minimal doses given for long periods of time or large doses given over short periods of time did not produce any pulmonary vascular lesions. Large doses of antibiotics administered for long experimental periods routinely produced a pulmonary vascular lesion in the medium-size and small-size pulmonary arterioles. The vasculitis consists of a diffuse eosinophilic infiltrate located perivascularly and throughout the intima and media. Associated with the vasculitis was a diffuse hyperplasia of the intima and media which frequently stenosed the vascular lumen. These studies suggest an association between large bolus dosages of antibiotics given over a prlonged period via a central catheter and a constrictive pulmonary arteriolar eosinophilic panvasculitis.

Death from pseudomembranous enterocolitis.

During the past 2 years at the Los Angeles County-University of Southern California Medical Center (LAC-USC), there have been 2 deaths from pseudomembranous enterocolitis. Each of these deaths occurred postoperatively in previously healthy women who received pronlonged antibiotic prophylasix. The implications of these poor therapeutic results are discussed. The distinctive clinical symptology of a patient with pseudomembranous enterocolitis is described, and current treatment recommendiations are presented.

Pharmacokinetic study of cefazaflur compared to cephalothin and cefazolin.

A single 1-Gm dose of cefazaflur, a new semisynthetic cephalosporin derivative, was compared in a crossover study to the same dose of cephalothin and cefazolin by intramuscular injection in seven healthy volunteers. Serum concentrations were measured at several time intervals during 6 hours following each administration. The mean peak serum levels obtained after 30 minutes were 25.2, 17.2, and 62.3 mug/ml, respectively, for cefazaflur, cephalothin, and cefazolin. In each of the seven subjects, serum concentrations were higher at each sampling time with cefazolin than with the other two cephalosporins. The percentage of total administered dose recovered in urine in a microbiologically active form for the 0-24-hour collection was, respectively, 92.7, 59.2, and 94.9 per cent with cefazaflur, cephalothin, and cefazolin, the largest part being excreted during the first 6 hours. Neither drug appeared to have any pronounced effect on various laboratory tests. Local reactions at the site of intramuscular injection were minor with cefazaflur and cefazolin, but were more pronounced with cephalothin.

Peripheral nerve injection injury: an experimental study.

In an attempt to answer questions regarding nerve injection injuries, we injected 11 agents in current use and commonly administered by intramuscular injection into the sciatic nerves of adult Wistar rats. Equal volumes of normal saline were used as control. We harvested the sciatic nerves at various times after injection and examined them by both light and electron microscopy. We performed myelinated nerve fiber counts and constructed histograms. Any impairment of motor function was also noted. We gave injections to 79 animals a total of 158 times; 116 injections were directly into the nerve fascicle (intrafascicular) and 42 were into the epineural tissue (extrafascicular). The results revealed considerable variation in the degree of nerve fiber injury according to the agent injected. Minimal damage resulted from the injection of iron-dextran, meperidine, and cephalothin, and maximal nerve injury followed the injection of penicillin, diazepam, and chlorpromazine. The site of injection was crucial. Intrafascicular injection was invariably associated with severe nerve injury, but, with few exceptions, extrafascicular injection resulted in minimal damage. The quantity of drug injected was also important in determining the degree of injury. Large, heavily myelinated fibers were more susceptible to injection injury than smaller, thinly myelinated nerve fibers. The effect of the injected drug seemed to be related to injury of the nerve fiber unit--both the axon and the Schwann cell with its myelin sheath. Regeneration in damaged nerves was a constant finding; even the most severely injured nerves, with total axonal degeneration, underwent subsequent regeneration.

Prophylactic antibiotics in hip fractures. A double-blind, prospective study.

Three hundred and seven patients, each of whom had a fracture of the proximal part of the femur, were studied in a randomized, double-blind fashion to determine whether perioperative administration of cephalothin would prevent postoperative infection. Major postoperative wound infections were significantly reduced in the cephalothin-treated group (4.7 per cent versus 0.7 per cent; p less than 0.05). There also was a reduction in the incidence of postoperative urinary-tract infections and a reduction in mean peak body temperatures. The duration of hospitalization was not affected and no hospital stay was prolonged by complications of antibiotic administration. However, in the cephalothin-treated group, a strong trend toward colonization by cephalothin-resistant organisms was noted.

[Acute hemorrhagic leucoencephalitis during tuberculosis (author's transl)]. / Leucoencéphalite aigue hémorragique au cours d'une tuberculose.

The authors report a fairly typical clinico-pathological case of acute hemorragic leucoencephalitis (A.H.L.E.). Both clinical and histological features appeared particularly acute. At autopsy a visceral evolving tuberculosis was diagnosed. Such an etiological circumstance has not been, apparently, reported in cases of A.H.L.E. published as such. Three other etiological circumstances were noticed: pyuria, treatment by cephalotin and treatment by gentamycine. The physiopathogenesis of A.H.L.E. remains obscure and will not be clarified before detailed immunological studies can be performed. But the disease is rare and brisk and diagnosis usually post-mortem.

Cephalothin induced neutropenia during the treatment of bacterial endocarditis.

The occurrence of cephalothin induced neutropenia in 3 patients with infective endocarditis is described. In each patient, withdrawal of cephalothin was followed by rapid haematological recovery. It is apparent that granulocytopenia may frequently occur in patients receiving prolonged, high dose, intravenous cephalothin for the treatment of bacterial endocarditis.

[Allergy to betalactamins. Diagnosis in vivo and correlations with tests in vitro (lymphocyte transformation and specific IgE) (author's transl)]. / L'allergie aux bêtalactamines. Protocole diagnostique in vivo. Corrélations avec les tests in vitro (T.T.L. et IgE spécifiques).

A comparative study of the results of skin tests and tests in vitro (lymphocyte transformation L.T. and R.A.S.T. for specific IgE) in 21 patients allergic to penicillin or penicillin-derivates revealed that tests in vivo are more sensitive and reliable than L.T. and R.A.S.T. This discordance needs future research for more valuable tests in vitro, such as specific histamine-release by leucocytes or determination of IgG4 reagins by R.A.S.T. procedure. A method of diagnosis of betalactamin hypersensitivity by skin tests, including penicilloylpolylysine, benzyl-penicillin, ampicillin and cephalosporin, is suggested; this method was experienced in 21 patients and 23 control subjects and proved to be safe and reproducible.

[Comparison of side effects of intravenous cephapirin and cephalothin with special reference to the incidence of phlebitis].

The frequency and severity of side effects, above all, phlebitis, associated with an intravenous use of cephapirin (CEPR) or cephalothin (CET) was compared in 69 patients with infections. Two grams of each drug were administered intravenously twice a day with a 21-G vein needle in one of the two arms of the patients. CEPR was administered to 32 patients, and CET to 37 patients respectively. After treatment, the status of the veins was checked, and laboratory findings and other side effects were evaluated daily. Each drug appeared to be equally efficacious in the treatment of infections. The administration of CEPR was associated with a slightly lower rate of phlebitis and other side effects, but the difference between the 2 drugs was not significant (0.05 less than P less than 0.10). Phlebitis was observed in 1 patient (3.1%) of CEPR group and in 3 patients (8.1%) of CET group. Side effects, including phlebitis, were observed in 4 patients (12.5%) of CEPR group and in 12 patients (32.4%) of CET group. In CET group, drug exanthema (3 cases), drug fever (3 cases), and abnormalities in liver function (4 cases) were observed. These findings, together with the results of other reports, suggest that CEPR is a safe and useful drug in the treatment of infection as compared with CET.

[Protein binding of various cephems in healthy subjects and patients with chronic renal failure].

This study was employed to investigate whether the serum protein binding of various cephems [cefpiramide (CPM), cefalotin (CET), latamoxef (LMOX)] differ among healthy subjects and patients with chronic renal failure (CRF) by means of in vitro equilibrium dialysis. The protein binding capacities of cephems in patients with CRF (hemodialysis, continuous ambulatory peritoneal dialysis, non-dialysis) decreased significantly compared to those in healthy subjects. The binding capacities correlated directly with total protein, albumin concentration and correlated inversely with blood urea nitrogen and serum creatinine concentration. In the study of protein binding during and after hemodialysis, the binding capacities of CPM and LMOX decreased immediately after dialysis and then increased with the time. However, the binding capacities of CET increased immediately after dialysis and then decreased. The binding capacities of CPM and LMOX correlated inversely with non-esterified fatty acids (NEFA) and those of CET correlated directly with NEFA. In the study of protein binding in pooled sera from healthy subjects with or without palmitic acid (PA), the binding capacities of CPM and LMOX decreased by increasing the concentration of PA, while those of CET increased by increasing PA up to 3 mM. The changes in binding capacity of cephems during and after hemodialysis have been possibly caused by increase of NEFA due to activation of lipase in use of heparin as an anticoagulant. In conclusion, changes in protein binding capacity of cephems in sera from CRF, which should be taken into consideration to avoid possible side effects.

Increasing urinary calcium excretion after ceftriaxone and cephalothin therapy in adults: possible association with urolithiasis.

In children, stone formation after ceftriaxone (CTRX) therapy by increasing calcium excretion was showed in the literature. In this study, we investigated the effect of CTRX, cephalothin (CP) and ampicillin (AS) therapy on urinary calcium excretion in adults. 180 participants included in the study who divided into six equal groups. The groups were; (1) CTRX therapy in stone free patients, (2) CTRX therapy in patients who have urinary stone; (3) CP therapy in stone free patients, (4) CP therapy in patients with urinary stone, (5) AS therapy in stone free patients, (6) AS therapy in patients with urinary stone. The patients received 2 g/day intravenous CTRX, CP and AS for 5 days in all groups respectively. There were no significant differences in demographic characteristics and blood biochemistry between the groups. Before and 5 days after the antibiotic therapies, the participants were evaluated by 24-h urinary calcium to creatinine ratio. Results were compared between the groups statistically by ANOVA and Tukey test. After drug therapies in group 2 and 4, the excretion of calcium to creatinine ratio in 24-h urine was more than the other groups. We found that both groups of two drugs therapy with or without stones (groups 1, 2, 3, 4), have significantly increased calcium to creatinine ratio in 24-h urine (p < 0.05). We did not find statistically difference in groups 5 and 6, after AS therapy. As a result of the study, we suggest that the patients who have taken antibiotic therapy with CTRX or CP, have an increased risk for the urolithiasis. In addition, we think that these drugs should be used carefully especially in patients with urolithiasis.