Combination Of Polymyxin Research Articles

Resistance to polymyxins: Mechanisms, frequency and treatment options

Polymyxins act by binding to lipid A moiety of the bacterial lipopolysaccharide and subsequently disintegrating the bacterial membranes. The most important mechanism of resistance includes modifications of the bacterial outer membrane structure, including lipopolysaccharide. Lipopolysaccharide modification is mostly mediated by PmrA/PmrB and PhoP/PhoQ two-component regulatory systems. These mechanisms exist with some differences in many gram-negative bacterial species. Resistance to polymyxins is generally less than 10%. In specific regions, such as the Mediterranean basin, Korea and Singapore, they tend to be higher. Heteroresistance to polymyxins is associated with exposure to polymyxins and especially suboptimal therapeutic dosage. Polymyxin combination regimens, tigecycline and fosfomycin may be useful options for the treatment of polymyxin-resistant gram-negative infections.

In Vitro Double and Triple Bactericidal Activities of Doripenem, Polymyxin B, and Rifampin against Multidrug-Resistant Acinetobacter baumannii , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli

In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.

Polymyxin B, in combination with fluconazole, exerts a potent fungicidal effect

The objective of this study was to identify existing clinical compounds that either possess a fungicidal activity alone or can act synergistically with fungistatic antifungals. We screened a clinical compound library for drugs that exhibited anti-Aspergillus activity. Among selected compounds, the cationic peptide antibiotic polymyxin B was chosen for further characterization because it can be used parenterally and topically. The fungicidal effect of polymyxin B and its synergistic interactions with azole antifungals were tested against a variety of fungal species. The toxicity of the drug combination of polymyxin B and fluconazole was compared with that of each drug alone in mammalian cell cultures. We found that polymyxin B possesses a broad-spectrum antifungal activity at relatively high concentrations. However, because of its synergistic interactions with azole antifungals, polymyxin B at much lower concentrations exerts a potent fungicidal effect against Cryptococcus neoformans, Candida albicans and non-albicans Candida species and moulds when combined with azoles. The combination of polymyxin B and fluconazole at concentrations within susceptible breakpoints is particularly potent against C. neoformans isolates, including fluconazole-resistant strains. The drug combination displayed no additional toxicity compared with polymyxin B alone when tested in cell culture. The combination of polymyxin B and fluconazole has the potential to be used in the clinic to treat systemic cryptococcosis. Our findings suggest that combining cationic peptide antibiotics with azole antifungals could provide a new direction for developing novel antifungal therapies.

Investigation on the Antiendotoxic Effect of the Combination of Polymyxin E and Ampicillin in Dogs with Endotoxic Pyometra

The aim of this study was to determine the incidence and levels of the gram negative bacterial endotoxin, and to investigate the effects of antiendotoxemic treatment along with operation. Thirty bitches with pyometra were used in this study. The bitches were randomly allocated into two groups as Group I (treated with polymyxin E-ampisillin) and Group II (treated with ampisillin). Samples for bacteriological examination were taken from vagina, vesica urinaria and uterus of all bitches. Blood samples were collected to evaluate biochemical, haematological tests and serum toxine levels before the operation and on 7 days after operation. Gelation was carried out to determine the gram negative bacterial endotoxin level with E-toxate test kit in accordance with gelation system. Gram negative bacteria were isolated 66% in Group I and 80% Group II. Escherichia coli were dominantly (63.4%) isolated from the uteri of 30 bitches with pyometra. Before the operation, serum toxin levels were found in Group I (n=10) 1.2±0.4 EU/ml and in Group II (n=12) 0.9±0.2 EU/ml. Five bitches in Group I and 3 bitches in Group II died on the third day after operation. Survival rate was a positive correlation with toxin levels (r=0.727; P<0.01) and BUN (r=0.539; P<0.01), creatinin (r=0.504, P<0.05) before operation in recovered and dead bitches. Serum toxin levels were not different between Group I (n=6; 0.14±0.02 EU/ml) and Group II (n=11; 0.19±0.01 EU/ml) 7 days after operation. Difference of toxin levels in both groups were different (P<0.05) between the preoperation period and the 7th day after operation. Before the operation and on the 7th day after the operation, in Group I difference between band neutrophil count and in Group II ALT, ALP, BUN, creatinin, RBC, WBC, Hct, band neutrophil and lenphocyte value were found significant (P<0.05). As a result, there was a positive correlation between toxin levels and BUN-creatinin values. Also, the cases that have the increased BUN and creatinin levels along with high toxin levels were trended towards to low survival rate. After operation, in cases that performed with ampicillin were acquired more effective results contrary to the hipothesis according to polymyxin E+ampicillin combination in bitches with pyometra.

Synergistic effects of miconazole and polymyxin B on microbial pathogens.

The therapeutic value of antibiotics depends on the susceptibility of the infecting microorganism and the pharmacological profile of the drugs. To assess the value of an antibiotic combination of polymyxin B and miconazole this study examined the in vitro synergistic potential of the two drugs on Gram-negative and Gram-positive bacteria and yeast. Antifungal and antibacterial activity was tested by minimum inhibitory concentration (MIC) of broth macrodilution and urea broth microdilution, by fluorescence microscopy and flow cytometry. Synergism was calculated using the fractional inhibitory concentration index (FICi). With Staphylococcus intermedius as target we found up to an eightfold reduction of the individual MICs when both drugs were combined. However, the FICi was 0.63 suggesting no real interaction between the two drugs. With Escherichia coli, Pseudomonas aeruginosa, and Malassezia pachydermatis as targets the antimicrobial drug combination reduced the MICs of polymyxin B and miconazole from fourfold to hundredfold resulting in FICi between 0.06 and 0.5 which defines a synergistic action. Thus, if polymyxin B and miconazole are combined their effect is greater than the sum of the effects observed with polymyxin B and miconazole independently, revealing bactericidal and fungicidal synergism. Our results indicate a strong therapeutic value for the combination of these antimicrobial agents against Gram-negative bacteria and yeast and a weaker value against Gram positive bacteria for clinical situations where these pathogens are involved.

143 The Effect of Various Antimicrobial Agents on Acinetobacter Baumannii: An In Vitro Evaluation

Background: Acinetobacter baumannii has recently emerged as an important hospital-acquired pathogen, especially in surgery, burn, and intensive care units. Due to its ability to develop resistance to antimicrobials, wound infection with A. baumannii is difficult to treat, and can lead to septicemia and even death. Use of appropriate topical antimicrobial agents in these circumstances could be one of the first steps in prevention of A. baumannii wound infection. Objectives: In this study, we will discuss the in vitro effects of seven common topical antimicrobial creams and dressings on A. baumannii. Methods: A. Baumannii ATCC# 6919 was subjected to sensitivity tests against mupirocin, silver sulfadiazine, mafenide acetate, a double antibiotic combination of polymyxin and bacitracin, a triple antibiotic combination of Neomycin, bacitracin and polymyxin, and two silver-containing dressings. Zones of inhibition were measured after 24 hours incubation period. Results and Conclusion: Of the evaluated antimicrobial agents, mafenide acetate was the most efficacious followed by mupirocin, triple and double antibiotic combinations in decreasing order. The silver-containing dressings yielded a lesser zone of inhibition as compared to the previously mentioned, and no zone of inhibition was observed using silver sulfadiazine. Further in vivo studies on the effect of antimicrobial agents against A. Baumannii are necessary to substantiate these findings and determine the potential clinical relevance of these therapies.

In Vitro Evaluation of the Antimicrobial Activity of Meropenem in Combination with Polymyxin B and Gatifloxacin Against Pseudomonas aeruginosa and Acinetobacter baumannii

The antimicrobial activity of meropenem combined with either polymyxin B or gatifloxacin was evaluated by the checkerboard method against Pseudomonas aeruginosa (10 strains) and Acinetobacter baumannii (10 strains). In addition, the triple combination of polymyxin B, gatifloxacin, and meropenem was also studied as well as the polymyxin B and gatifloxacin combination. A partial synergism interaction between meropenem and polymyxin B was observed for 80% of the A. baumannii strains. In contrast, this combination showed an indifferent effect for 80% of the P. aeruginosa strains tested. The combination of meropenem and gatifloxacin showed synergism only for two strains of A. baumannii, and partial synergism and additive effect for seven strains and indifference for four strains of both species. For the strains of P. aeruginosa, the double combination of polymyxin B and gatifloxacin and the triple combination of meropenem, polymyxin B and gatifloxacin were indifferent for the majority of the strains tested, that is, 90 and 80% respectively.

Effects of Commonly Used Topical Antimicrobial Agents onAcinetobacter baumannii: An In Vitro Study

Acinetobacter baumannii has recently emerged as an important pathogen among wounded soldiers in Iraq. Because of its ability to develop resistance to antimicrobial agents, wound infections with A. baumannii are difficult to treat and can lead to septicemia and even death. Use of appropriate topical antimicrobial agents in these circumstances could be one of the first steps in the prevention of A. baumannii wound infections. In this study, we present the in vitro effects of seven common topical antimicrobial creams and dressings on A. baumannii. A. baumannii was subjected to sensitivity tests with mupirocin, silver sulfadiazine, mafenide acetate, a double-antibiotic combination of polymyxin and bacitracin, a triple-antibiotic combination of neomycin, bacitracin, and polymyxin, and two silver-containing dressings. Zones of inhibition were measured after 24 hours of incubation. Of the evaluated antimicrobial agents, mafenide acetate was the most efficacious, followed by mupirocin and triple- and double-antibiotic combinations (in decreasing order). The silver-containing dressings yielded smaller zones of inhibition, compared to the previously mentioned agents, and no zone of inhibition was observed with silver sulfadiazine. Further in vivo studies on the effects of antimicrobial agents against A. baumannii are necessary to substantiate these findings and to determine the potential clinical relevance of these therapies.

Synergy testing of multidrug resistant Acinetobacter baumanii against tigecycline and polymyxin using an E-test methodology

The emergence of multi drug resistant nosocomial Acinetobacter baumanii infection has prompted the evaluation of newer antimicrobial agents and older warehoused agents as possible therapeutic candidates. In addition to the carbapenems, two other agents have emerged in clinical use and the in-vitro literature as potential therapeutic agents. In a number of studies tigecycline, a new agent in the glycylcycline class, related to minocycline, and polymyxin B, a polypeptide antibiotic used parenterally in the past as a gram negative rod antimicrobial, have show promising activity against multidrug resistant A. baumanii isolates, including those isolates resistant to the carbapenems [1–3]. Tigecycline appears to be bacteriostatic in vitro and in one published clinical study there has been breakthrough bacteremia. Very little in vitro data exists on the activity of the combination of polymyxin plus tigecycline against multidrug resistant A. baumanii [4, 5]. The E-test methodology has proven reliable for in vitro antimicrobial sensitivity testing [6]. A modified E-test methodology for performing antimicrobial synergy tested has been preliminarily evaluated in the literature and although not extensively validated, has been found to correlate well with traditional checkerboard and time-kill methodologies in several studies [7, 8]. E-test synergy testing is performed by crossing the E-test strips for the 2 test antimicrobials at a 90° angle at their predetermined MIC value on an inoculated Mueller Hinton agar plate. The plates are then incubated for 24 h at 35°C. The MIC of each antimicrobial in combination is interpreted as the value at which the zone of inhibition intersects the E test strip. The fractional inhibitory concentration index (FICI) is calculated and interpreted for synergy, indifference or antagonism. The FICI=MICtigecycline in combination/MICtigecyclinealone+ MICpolymixin in combination/MICpolymixin alone. The FICI is interpreted as follows: 4.0 indicates antagonism. We tested 19 recent clinical isolates of multidrug resistant A. baumanii from a large university teaching hospital for susceptibility to tigecycline and polymyxin B and performed synergy testing on the combination using E-test methodology. Clinical sources of the isolates were as follows: respiratory 9/19 (47.4%), urine 6/19 (31.6%), blood 2/19 (10.5%), wound 2/19 (10.5%). E-test synergy testing, revealed FICI values for tigecycline plus polymyxin between 0.88 and 2.0 for all 19 isolates, with 11/19 isolates having an FICI of 2.0. The FICI distribution was as follows:

Characterization of the Zinc-Containing Metalloprotease Encoded by zpx and Development of a Species-Specific Detection Method for Enterobacter sakazakii

Enterobacter sakazakii causes a severe form of neonatal meningitis that occurs as sporadic cases as well as outbreaks. The disease has been epidemiologically associated with consumption of reconstituted, dried infant formulas. Very little information is available regarding pathogenicity of the organism and production of virulence factors. Clinical and environmental strains were screened for production of factors which have activity against Chinese hamster ovary (CHO) cells in tissue culture. Polymyxin B lysate and sonicate preparations but not culture supernatants from the strains caused "rounding" of CHO cells. Subsequent studies showed that the CHO cell-rounding factor is a proteolytic enzyme that has activity against azocasein. The cell-bound protease was isolated by using a combination of polymyxin B lysis, followed by sonication of cells harvested from tryptone broth. The protease was purified to homogeneity by sequential ammonium sulfate precipitation, gel filtration chromatography with Sephadex G-100, hydrophobic interaction chromatography with phenyl-Sepharose CL-4B, and a second gel filtration with Sephadex G-100. In addition to activity against azocasein, the purified protease also exhibits activity against azocoll and insoluble casein but not elastin. The protease has a molecular weight of 38,000 and an isoelectric point of 4.4. It is heat labile and for maximal activity against azocasein has an optimum temperature of 37 degrees C and a pH range of 5 to 7. Proteolytic activity is inhibited by ortho-phenanthroline and Zincov but is not affected by phenylmethylsulfonyl fluoride, N-ethylmaleimide, and trypsin inhibitors, which demonstrates that the protease is a zinc-containing metalloprotease. The metalloprotease does not hemagglutinate chicken or sheep erythrocytes. Twenty-three to 27 of the first 42 N-terminal amino acid residues of the metalloprotease are identical to proteases produced by Serratia proteamaculans, Pectobacterium carotovorum, and Anabaena sp. PCR analysis using primers designed from a consensus nucleotide sequence showed that 135 E. sakazakii strains possessed the metalloprotease gene, zpx, and 25 non-E. sakazakii strains did not. The cloned zpx gene of strain 29544 consists of 1,026 nucleotides, and the deduced amino acid sequence of the metalloprotease has 341 amino acid residues, which corresponds to a theoretical protein size of 37,782 with a theoretical pI of 5.23. The sequence possesses three well-characterized zinc-binding and active-site motifs present in other bacterial zinc metalloproteases.

Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence

Several reports have described the use of polymyxins by the intraventricular or intrathecal route for multidrug-resistant Gram-negative meningitis. We reviewed the available clinical evidence regarding intraventricular/intrathecal administration of polymyxins in patients with meningitis, focusing on effectiveness and safety. Relevant studies were identified from PubMed (January 1950 to April 2006) as well as from the references of relevant articles. We identified 31 case reports/series that matched our inclusion criteria. Sixty-four episodes of Gram-negative meningitis (34 in adults) were reviewed. Monotherapy with polymyxins via the intraventricular or intrathecal route was used in 11 episodes and combination of systemic and local polymyxins was used in 25 episodes. In the remaining episodes, various combinations of local polymyxins with systemic and/or local antibiotics were administered. Cure was achieved in 51/64 episodes (80%); in 26/30 episodes (87%) due to Pseudomonas aeruginosa and in 10/11 episodes (91%) due to Acinetobacter spp. Toxicity related to local administration of polymyxins was noted in 17/60 (28%) patients. The most common toxicity was meningeal irritation (12 cases). Discontinuation of treatment was necessary in four episodes and dose reduction in four episodes; irreversible toxicity was not reported. The limited available evidence suggests that therapy with intraventricular/intrathecal polymyxins alone or in combination with systemic antimicrobial agents is effective against Gram-negative meningitis. Toxicity is not uncommon but it is dose-dependent and reversible. Further studies are needed to evaluate the criteria for initiation of local central nervous system treatment with polymyxins, the optimal dosages and the role of adjuvant systemic or local therapy.

Toxic Keratolysis from Combined use of Nonsteroid Anti-Inflammatory Drugs and Topical Steroids following Vitreoretinal Surgery

To evaluate the corneal complications associated with the combined use of non-steroid anti-inflammatory drugs (NSAIDs) and topical steroids following vitreoretinal surgery. Description of corneal lesions in three patients after vitrectomy with use of topical ketorolac and prednisolone acetate. Three eyes of three patients developed an atrophic central corneal ulcer with stromal thinning following a pars plana vitrectomy under local anesthesia. Lesions were asymptomatic and were found during a routine examination 2, 3, and 8 weeks after surgery, respectively. Surgical indications were as follows: a preretinal membrane, choroidal neovascularization, and massive uveal effusion following cataract surgery. Topical postoperative treatment was as follows: ketorolac 4 times a day, a combination of prednisolone acetate, polymyxin B, and neomycin 6 times a day, and 1% cyclopentolate 3 times a day. Suspension of ketorolac and ocular occlusion led to the resolution of corneal lesions between 2.5 and 3 months later, yielding a central superficial scarring, which showed no changes after a follow-up of 3 years. Toxic keratolysis may appear as a secondary effect of the combined use of topical NSAIDs and steroids following vitreo retinal surgery and must be taken into account in the differential diagnosis of postoperative corneal lesions.

Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents

To describe the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae in Brooklyn, NY and assess the in vitro activity of various antibiotic combinations. Clinical isolates with suspected carbapenem resistance were referred to the central research laboratory from August 2003 to June 2004. Isolates underwent MIC testing, ribotyping, and were analysed for the presence of KPC carbapenemases. Time-kill studies using various antibiotic(s) were performed on selected isolates. Ninety-six isolates were referred from 10 Brooklyn hospitals. All isolates were resistant to the carbapenems with most having MICs >32 mg/L. Few were susceptible to fluoroquinolones and cephalosporins; approximately half were susceptible to aminoglycosides, and 90% to polymyxin B. Two-thirds were susceptible to doxycycline, and all were considered susceptible to the investigational glycylcycline antibiotic tigecycline. Virtually all possessed bla(KPC), and over 80% belonged to one ribotype. In time-kill studies involving 16 isolates, tigecycline demonstrated bacteriostatic activity and polymyxin B concentration-dependent bactericidal activity. The combination of polymyxin B at 0.5 x MIC plus rifampicin had synergic activity against 15/16 isolates, including two polymyxin-resistant strains. The combination of polymyxin B plus imipenem had synergic bactericidal activity against 10/16 isolates, but was antagonistic for three isolates. Multiresistant K. pneumoniae with bla(KPC) are present in multiple hospitals in New York City. The most consistently active agents in vitro were tigecycline and polymyxin B, particularly when the latter was combined with rifampicin. The clinical efficacy of these agents remains to be determined.

Citywide emergence of Pseudomonas aeruginosa strains with reduced susceptibility to polymyxin B

To determine the prevalence of Pseudomonas aeruginosa isolates with reduced susceptibility to polymyxin B, and to assess the in vitro activity of antibiotic combinations. All unique patient isolates of P. aeruginosa were collected from 11 Brooklyn, NY hospitals during a three month period in 2003. Isolates with reduced susceptibility to polymyxin B (MIC > 2 mg/L) underwent ribotyping. The activity of polymyxin B combined with rifampicin, azithromycin and/or imipenem was tested by the chequerboard and time-kill methods against a subset of isolates. Of 527 isolates, only 61% were susceptible to imipenem. Twenty-five isolates (5%), from 8/11 hospitals, had reduced susceptibility to polymyxin B (MICs 4-8 mg/L), compared with 0/691 isolates collected in 2001. Ten of 25 were resistant to multiple other antibiotic classes. Ribotyping of the isolates revealed 19 unique types. Chequerboard testing of the 10 multiresistant isolates demonstrated synergy for the combinations of polymyxin B with azithromycin, imipenem and rifampicin in 6, 2, and 1 isolates, respectively. Time-kill studies revealed bactericidal activity for the following antibiotics when combined with polymyxin B: imipenem plus rifampicin against all 10 isolates, rifampicin in 9/10 isolates, imipenem in 8/10 isolates and azithromycin in 4/10 isolates. MICs of bacteria surviving incubation in polymyxin B alone rose for 4/9 isolates (MIC range 12-48 mg/L). P. aeruginosa with reduced susceptibility to polymyxin B have emerged in multiple strains in Brooklyn, NY. Combinations of polymyxin B with rifampicin and/or imipenem are bactericidal. The clinical utility of these combinations remains to be determined.

In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii.

Eight unrelated clinical Acinetobacter baumannii isolates resistant to all commonly used antibiotics were subjected to three-dimensional checkerboard microtiter plate dilution and time-kill studies at one-fourth of their MICs of polymyxin B, imipenem, and rifampin. Synergy was demonstrated with combinations of polymyxin B and imipenem, polymyxin B and rifampin, and polymyxin B, imipenem, and rifampin. Double combinations of polymyxin B and imipenem and of polymyxin B and rifampin were bactericidal for seven of eight isolates, and triple combinations were bactericidal for all isolates within 24 h. Future clinical studies using double and triple therapy with these antibacterials may provide an effective option against potentially lethal infection due to multiresistant Acinetobacter baumannii.

Controlled multicenter study on chronic suppurative otitis media treated with topical applications of ciprofloxacin 0.2% solution in single-dose containers or combination of polymyxin B, neomycin, and hydrocortisone suspension

Otic drops of either ciprofloxacin 0.2% solution (CIP) or a combination of polymyxin B, neomycin, and hydrocortisone suspension (PNH) were administered for 6 to 12 days to patients (14-71 years old) with chronic suppurative otitis media in a randomized, nonblinded, multicenter clinical trial. Two hundred thirty-two enrolled patients were analyzed for efficacy on a “per protocol” basis. The most frequently identified causal agents were Staphylococcus aureus (28% of the patients), Pseudomonas aeruginosa (19%), and Staphylococcus sp (9%). Clinical success was observed in 91% and 87% of the CIP-and PNH-treated patients, respectively. At 1-month follow-up, 4% of CIP and 6% of PNH patients showed a relapse of otorrhea. Bacteriologic eradication was seen in 89% and 85% of patients in the CIP and PNH groups, respectively. At 1-month follow-up, reinfection or recurrence of infection appeared in 3 patients in the PNH group and in 1 patient in the CIP group. Both treatments were well tolerated. The most frequently reported adverse events were pruritus, stinging, and earache. Audiometric tests did not show changes attributable to study drugs in any but 1 patient in the PNH group. This clinical trial shows that topical 0.2% ciprofloxacin solution in single-dose containers is effective and well tolerated in patients with chronic suppurative otitis media. (Otolaryngol Head Neck Surg 2000;123:617-23.)

Topical Antibiotics on Tracheostoma Prevents Exogenous Colonization and Infection of Lower Airways in Children

Patients requiring long-term ventilation are at high risk of lower airway infections, generally of endogenous development. Patients on long-term ventilation, in particular via a tracheostomy, may develop tracheobronchitis or pneumonia of exogenous pathogenesis, ie, caused by microorganisms not carried in the oropharynx. The frequency of exogenous colonization or infection has previously been reported to be as high as 33%. A prospective observational cohort study of 2 years was undertaken to evaluate the efficacy of topical antibiotics in the prevention of exogenous colonization or infection of the lower airways. The antibiotic combination of polymyxin E and tobramycin in a 2% paste was applied four times a day on the tracheostoma. A total of 23 children (median age, 4.1 months; range, 0 to 215 months) were enrolled in the study from September 1, 1996, until August 30, 1998. Surveillance samples of the oropharynx were obtained before tracheostomy and thereafter twice weekly. Diagnostic samples of the lower airways were taken once weekly and on clinical indication. Fourteen children (61%) had a total of 16 episodes of tracheal colonization or infection with 20 potentially pathogenic microorganisms. Only one child had tracheobronchitis with Streptococcus pneumoniae and Haemophilus influenzae during the 2-year study. Of the 16 colonization episodes, 12 (75%) were of primary endogenous pathogenesis, ie, caused by microorganisms present in the oropharynx at the time of tracheostomy. Community microorganisms including S pneumoniae, H influenzae, Moraxella (Branhamella) catarrhalis, and Staphylococcus aureus were the predominating bacteria. Three patients acquired nosocomial bacteria Pseudomonas aeruginosa and Hafnia alvei in the oropharynx, subsequently followed by secondary colonization of the lower airways. There was one failure of the prophylaxis: one patient (4%) had exogenous colonization with Pseudomonas pickettii. Topical antibiotics applied to the tracheostoma were found to be effective in reducing the exogenous route of colonization of the lower respiratory tract, compared with clinical experience and the literature. This promising technique requires further evaluation in randomized trials.

A Cluster of Nosocomial Cross-Infection Due to Multiple Antibiotic-Resistant Acinetobacter baumannii:Characterization of the Strain and Antibiotic Susceptibility Studies

A multiple antibiotic-resistant (MAR) strain of Acinetobacter baumannii caused nosocomial cross-infection among 3 patients of a surgical intensive care unit. The isolates were of identical biochemical profile (77776 S–U–) and serotype (serovar 36) and identical in terms of pulsed-field gel electrophoresis macrorestriction (SmaI, ApaI) analysis. This MAR strain was susceptible only to netilmicin, tobramycin, imipenem, meropenem, polymyxin B, and trovafloxacin. The minimal bactericidal concentrations of imipenem and meropenem were markedly higher than the corresponding minimal inhibitory concentrations against this strain. Combined fresh defibrinated human blood (65 vol%) and antimicrobial drug assays yielded the following results: polymyxin was the most rapidly bactericidally effective antibiotic in the presence of blood and in broth. Tobramycin and netilmicin were efficacious in 65 vol% blood. Imipenem was slightly more effective than meropenem in broth, whereas both carbapenems sterilized blood-containing assay tube contents. Trovafloxacin failed to achieve bactericidal activity (to 99.9% kill) in the presence of blood, presumably because this strain was resistant to ciprofloxacin and borderline susceptible to ofloxacin. Trovafloxacin combined with either imipenem or meropenem yielded an indifferent effect. However, the combination of trovafloxacin (2 μg/ml) plus tobramycin (1 μg/ml) achieved sterilization of tube contents in the presence of blood within 4 h after exposure and in broth following extended (overnight) incubation. This MAR strain of A. baumannii was high-level resistant to rifampin; thus the combination of polymyxin B plus rifampin proved indifferent.

Topical irrigation with polymyxin and bacitracin for spinal surgery

BACKGROUND The purpose of the present study was to evaluate constant irrigation with saline containing 50,000 units each of polymyxin and bacitracin in a regimen of antimicrobial prophylaxis for clean spinal surgery at two community hospitals with a zero infection rate. METHODS The focus was on the bactericidal effects of prophylactic topical antibiotics by assessing random contamination in neurosurgical wounds from: 1) the flora of the integument and nares of the operating team, 2) the surgical apparel, 3) the patient’s skin, 4) air-borne organisms in the operating theater, and 5) the surgeon’s gloves. RESULTS Based on individual biotyping of bacteria and antimicrobial sensitivity testing, no consistent source or pattern could be uncovered for the organisms recovered from the operative site. Relying on longitudinal data, the incidence of intraoperative bacterial growth with continuous saline lavage was reduced from 64 to 4% when the combination of topical polymyxin and bacitracin was added. CONCLUSIONS Although the virtual elimination of bacterial growth in the surgical site was accomplished, the efficacy of topical antibiotics in the prevention of wound infection remains unproven.

Use of Antibiotics for Expansion of the Merocel® Packing following Endoscopic Sinus Surgery

Sinus packs that are used for hemostasis and the prevention of synechiae following endoscopic sinus surgery frequently get colonized with bacteria from the infected sinus, which increases the risk for infection. This study was conducted in an attempt to characterize the bacterial flora of the chronically infected sinus, and to evaluate whether direct installation of antibiotics into the sponge inhibits bacterial growth. Bacteria were cultured from 89% of the sinuses at surgery, and in 67% of the cases, the same bacteria were recovered from the sinus dressings one week later. When the Merocel sinus dressing was expanded with a combination of polymyxin, neomycin and hydrocortisone at the time of surgery, a 36% decrease in bacterial growth was observed, along with a decrease in the severity of pain associated with removal of the pack. This supports the concept of using an antibiotic for the expansion of the sponge following endoscopic sinus surgery.