Impact of the HIV epidemic and Anti-Retroviral Treatment policy on lymphoma incidence and subtypes seen in the Western Cape of South Africa, 2002-2009: preliminary findings of the Tygerberg Lymphoma Study Group.

The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and a roll-out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish the impact of HIV epidemic and the ARV roll-out treatment program on the incidence of HIV Related Lymphoma (HRL). Early data document that despite the ART roll out, cases of HRL are increasing in this geographical location, now accounting for 37% of all lymphomas seen in 2009 which is an increase from 5% in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B-cell lymphoma subtypes. The reasons for this observed increase in HRL are not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnoses are made has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reasons, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression.

Selective sputum cultures. A bronchial culture technique using a modified nasotracheal suction catheter with a sterile, inner telescoping cannula.

The contamination of expectorated or catheter-aspirated sputum specimens by pathogenic microorganisms which have colonized the nose and oropharynx remains a formidable obstacle to the accurate interpretation of sputum cultures. This problem is encountered in all forms of acute and chronic bronchopulmonary infection. A standard suctioning technique via a nasotracheal catheter has been modified with a telescoping sterile inner cannula to obtain uncontaminated bronchopulmonary secretions for culture. Bacteriologic results of selective bronchial cultures obtained in 18 patients following major chest surgery have provided important considerations concerning the prophylactic use of antibiotics. The telescoping cannula method is a simple, safe, and practical means of selectively monitoring the bacteriologic flora of the lower respiratory tract.

Neonatal airway colonization with gram-negative bacilli: association with severity of bronchopulmonary dysplasia.

BACKGROUND: Airway colonization with Gram-negative bacilli (GNB) and Gram-positive cocci (GPC) is common in mechanically ventilated neonates. Whether GNB are related to nosocomial bloodstream infection (BSI) and/or to the severity of bronchopulmonary dysplasia (BPD) is unknown. METHODS: We prospectively examine this relationship using a cohort design. Data from 260 < or = 1250-g birth weight inborn infants (1991 to 1995) intubated > or = 2 weeks included 917 serial tracheal cultures and 583 blood cultures. The severity of BPD was assessed by duration of mechanical ventilation, oxygen dependency at 36 weeks of postconceptional age and the use of home oxygen supplementation. RESULTS: After 2 weeks of ventilation, 80% of the infants were colonized with GPC (Staphylococus epidermidis and Staphylococcus haemolyticus in 90% of the cases). Superimposed on 36% of these infants was GNB airway colonization with Klebsiella pneumoniae (25%), Enterobacter cloacae (25%), Escherichia coli (25%), Pseudomonas aeruginosa (10%), Serratia marcescen (10%), Acinetobacter baumannii and Haemophilus influenzae (5%). Comparison between 174 GPC- and 86 GNB-colonized infants showed that demographics, birth weight, gestational age, perinatal risk factors and mortality were similar. Fifteen percent of GNB-colonized infants developed BSI caused by GNB and 14% developed BSI caused by GPC. No significant temporal relationship between airway colonization and BSI was noted. GNB infants were ventilated longer and required oxygen at 36 weeks of postconceptional age and home oxygen supplementation twice as often as infants colonized only with GPC. GNB colonization was a predictor of severe BPD after controlling for ventilation. Ureaplasma colonization occurred in 28% of GNB-colonized and 33% of noncolonized infants and was not a predictor of BPD severity. CONCLUSION: GNB airway colonization creates a moderate risk for BSI. Antibiotic treatment does not regularly eradicate GNB. GNB airway colonization is associated with severe BPD, but further studies will be necessary before therapeutic efforts to eradicate GNB from the airways should be undertaken.

Bloodstream infections in a neonatal intensive-care unit: 12 years' experience with an antibiotic control program.

OBJECTIVE: To assess the prevalence of gram-positive coccal (GPC), gram-negative bacillary (GNB), and fungal blood-stream infections (BSIs) during a 12-year period in which a consistent antibiotic treatment protocol was in place; to evaluate the efficacy of these antibiotic policies in relation to treatment, to the emergence of bacterial or fungal resistance, and to the occurrence of infection outbreaks or epidemics. STUDY DESIGN: Case series. METHODS: Demographic, clinical, and bacteriological information from 363 infants born during 1986 through 1991 and 1992 through 1997 who developed 433 blood-culture-proven BSIs was analyzed. Early-onset BSIs were defined as those infections discovered within 48 hours of birth, and late-onset BSIs as those that occurred thereafter. Suspected early-onset BSIs were treated with ampicillin and gentamicin, and suspected late-onset BSIs with vancomycin and gentamicin. Antibiotics were changed on the basis of organism antimicrobial susceptibility. RESULTS: Early-onset BSIs were noted in 52 of 21,336 live births and 40 of 20,402 live births during 1986 through 1991 and 1992 through 1997, respectively. GPC (83% due to group B streptococcus [GBS]) accounted for approximately one half of early-onset BSI cases and GNB (68% Enterobacteriaceae) for the remainder. Early-onset GBS declined from 24 to 11 cases (P=.04) and late-onset BSI increased from 111 to 230 cases (P<.01) from the first to the last study period. Sixty-eight percent of late-onset BSIs were due to GPC (primarily coagulase-negative Staphylococcus), 18% to GNB, and 14% to fungus. Over the study period, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa isolated from the newborn intensivecare unit (unlike those strains from other hospital units) remained fully susceptible to ceftazidime and gentamicin. Although the hospitalwide prevalence of methicillin-resistant Staphylococcus aureus increased, all 17 newborn BSI cases were due to methicillin-sensitive strains. Prevalence of methicillin-resistant coagulase-negative Staphylococcus increased, although all strains remained vancomycin-susceptible, as did the 16 Enterococcus faecalis isolates. All fungi recovered (from 48 patients) were susceptible to amphotericin. CONCLUSION: We observed a decrease in the prevalence of early-onset BSIs due to GBS and an increase in late-onset BSIs due to GPC, GNB, and fungi. The combination of ampicillin and gentamicin for suspected early-onset BSIs and vancomycin and gentamicin for late-onset BSIs has been successful for treatment of individual patients without the occurrence of infection outbreaks or the emergence of resistance. Controlled antibiotic programs and periodic evaluations based on individual unit and not on hospitalwide antibiograms are advisable.

Mycobacterium fortuitum infection of a Hickman catheter site.

A patient with histiocytic lymphoma who developed a Hickman catheter exist site infection due to Mycobacterium fortuitum is described. Due to the risk of dissemination in immunosuppressed patients and the resistance to antibiotic therapy, rapid-growing mycobacteria should be considered when gram-positive bacilli are associated with infections in patients with these catheters.

Failure of systemic antibiotics to eradicate gram-negative bacilli from the airway of mechanically ventilated very low-birth-weight infants.

BACKGROUND: Gram-negative bacillary (GNB) airway colonization in mechanically ventilated newborns is associated with morbidity and mortality, which may be reduced if systemic antimicrobial therapy eradicates GNB from the airway. Efforts to do so in adults have met with variable success; similar experiences in newborns have not been reported. METHODS: From 1991 through 1998, 531 very low-birth-weight infants were mechanically ventilated longer than 2 weeks. The study group was 106 infants with GNB airway colonization. Sixty-four other neonates in whom GNB nosocomial bloodstream infections developed served as antibiotic treatment outcome control. RESULTS: Isolated from the airway were enteric (70 cases) and environmental (36 cases) GNB. Gentamicin alone or with ceftazidime (79), ceftazidime (11), piperacillin in combination with tazobactam or tobramycin (8), and tobramycin, in combination with ampicillin/sulbactam or mezlocillin (8) were the antimicrobials selected. Systemic antibiotics failed to eradicate GNB colonization in 97% of the cases. Six of the 106 infants with airway colonization died for reasons unrelated to infection. Sixty-four infants experienced 67 bloodstream infections as a result of enteric (53) and environmental (14) GNB. Gentamicin alone (23), with ceftazidime (26), or with clindamycin or ampicillin/sulbactam (9), piperacillin with tazobactam or tobramycin (3) and ceftazidime alone (6) were the antimicrobials selected. Survival occurred in 84% of the 67 nosocomial bloodstream infections. CONCLUSIONS: Systemic antibiotics do not consistently eradicate GNB from the airway of mechanically ventilated newborns, therefore its empirical use for prophylaxis or treatment of airway colonization should be discouraged.

Ventilator-associated pneumonia in very low-birth-weight infants at the time of nosocomial bloodstream infection and during airway colonization with Pseudomonas aeruginosa.

PURPOSE: To study retrospectively the incidence of ventilator-associated pneumonia (VAP) at the time of Pseudomonas aeruginosa nosocomial bloodstream infection (BSI) and at the time of P aeruginosa airway colonization. MATERIALS AND METHODS: Fifteen very low-birth-weight infants who had P aeruginosa BSI and 33 others who did not but who had P aeruginosa airway-colonization were studied. We correlated clinical data, blood cultures (BCs), and tracheal cultures (TCs) with radiologic findings from radio-graphs taken within 2 days before, the day of, and 1 day after BCs or TCs were first positive for P aeruginosa. Chest radiographs were graded by using semiquantitative scores for bronchopulmonary dysplasia and for pneumonia. RESULTS: Mean birth weight, gestational age, and age when BC or TC became positive were similar for patients with BSI and colonization. At the time of BSI, 2 infants had airway colonization with P aeruginosa; the TCs of the remaining 13 grew P aeruginosa as a new pathogen. Thirteen of 15 patients with BSI, but none of 33 infants with colonization, died within 2 days of positive BC. VAP was diagnosed in 13 of 15 patients with BSI and in 3 of 33 infants with colonization. CONCLUSION: Mechanically ventilated very low-birth-weight infants whose TCs yield P aeruginosa but whose BCs remain negative infrequently have VAP are presumed airway-colonized and are expected to survive. Conversely, VAP is likely to be found when BCs and TCs simultaneously grow P aeruginosa, and high mortality is anticipated.

Does extra-amniotic infection cause preterm labor? Gas-liquid chromatography studies of amniotic fluid in amnionitis, preterm labor, and normal controls.

Gas-liquid chromatography (GLC) was used to identify short-chain organic acid byproducts of bacterial metabolism in amniotic fluid from seven normal control patients, six women with overt amnionitis, and six preterm labor patients. Microbiologic culture for aerobic and anaerobic bacteria was also carried out. Positive GLC findings were generally associated with positive cultures, except in five of the preterm labor patients whose GLCs were positive despite negative cultures. The origin of the short-chain organic acids found in these women is unclear; extra-amniotic bacterial growth may explain this finding.

The utility of non-beta-lactam antimicrobial MICs as markers to distinguish oxacillin-resistant from oxacillin-susceptible strains of Staphylococcus epidermidis.

Among 6,068 strains of Staphylococcus epidermidis, 75.5% were oxacillin-resistant. Oxacillin-susceptible strains were more frequently susceptible to erythromycin, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, and tetracycline than oxacillin-resistant strains. With the exception of erythromycin, non-beta-lactam MICs were less discriminatory for identifying oxacillin-resistant strains with oxacillin MICs < or = 2 micrograms/ml than for those with oxacillin MICs > or = 4 micrograms/ml.

Imipenem (N-formimidoyl thienamycin): in vitro antimicrobial activity and beta-lactamase stability.

In vitro studies with imipenem (N-formimidoyl thienamycin or MK0787) were performed with 8481 clinical isolates in three separate medical centers. More extensive comparative studies were also performed with 605 representative isolates, comparing imipenem to six other beta-lactams. Although the newer beta-lactams were often more active against susceptible species, imipenem demonstrated the broadest spectrum of antibacterial activity, with MIC 90s less than or equal to 4.0 micrograms/ml for all species tested except Pseudomonas maltophilia and P. cepacia. Imipenem was very active against all streptococci and staphylococci, in contrast to the third-generation cephalosporins. There was no evidence of cross-resistance between imipenem and the cephalosporins or penicillins. Resistance to hydrolysis by seven beta-lactamase preparations was documented for imipenem, cefotaxime, and moxalactam. Like many other beta-lactams, imipenem inhibited the Type I beta-lactamase produced by Enterobacter cloacae. Other beta-lactamases from gram-negative bacilli were also inhibited by high concentrations of imipenem.

Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations for MIC quality control.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.

In vitro evaluation of cefixime (FK027, FR17027, CL284635): spectrum against recent clinical isolates, comparative antimicrobial activity, beta-lactamase stability, and preliminary susceptibility testing criteria.

Cefixime, a new orally absorbed cephalosporin, was compared by in vitro testing with other oral beta-lactams, including cephalexin, cefaclor, cefuroxime, amoxicillin, and amoxicillin + clavulanate. Enterobacteriaceae were inhibited by lower concentrations of cefixime than any of the reference drugs; 90% and 95% were inhibited by less than or equal to 1.0 and less than or equal to 8.0 micrograms/ml, respectively. Cefixime was the least active among these drugs against staphylococci, with only 31% of 1106 strains inhibited by less than or equal to 8.0 micrograms/ml and less than 1% by less than or equal to 1.0 microgram/ml. Enterococci and pseudomonads were not susceptible to any of the drugs tested. Penicillin-resistant pneumococci were relatively resistant to cefixime, but penicillin-susceptible pneumococci were very susceptible to cefixime. Other streptococci were generally susceptible to all compounds tested, with relative activities of amoxicillin greater than cefaclor and cefuroxime greater than cefixime greater than cephalexin. Cefixime was inactive against Bacteroides species. A slight inoculum effect occurred with cefixime with inocolum concentrations varying from 10(5) to 10(6) colony forming units per milliliter, but this was more marked at 10(7) colony forming units per milliliter. Cefixime was resistant to hydrolysis by seven common beta-lactamases. It inhibited the hydrolysis of nitrocefin only by type 1 cephalosporinases. The disk diffusion zone diameter breakpoints for the 30-micrograms cefixime disk were determined by regression analysis to be greater than or equal to 27 mm (susceptible) and less than or equal to 23 mm (resistant), respectively corresponding to minimal inhibitory concentration breakpoints of less than or equal to 1.0 and greater than or equal to 4.0 micrograms/ml. Because of the high interpretive error rate (13.8%) and the occurrence of these breakpoints on the parabolic portion of the regression curve, we recommend further evaluation of cefixime disks with lower potencies.

In vitro activity of carumonam (RO 17-2301), BMY-28142, aztreonam, and ceftazidime against 7,620 consecutive clinical bacterial isolates.

For 45-60 days four geographically separate clinical laboratories tested routine clinical bacterial isolates for susceptibility to carumonam, aztreonam, BMY-28142, and ceftazidime by the broth microdilution method. All four drugs were highly active against Enterobacteriaceae, inhibiting greater than 96% of the 4887 strains tested at less than or equal to 8.0 microgram/ml. The minimal inhibitory concentration at which 50% of the isolates were inhibited for each drug was less than or equal to 0.125 micrograms/ml. Ceftazidime was the most active against nonenteric gram-negative bacilli (86% inhibited at less than or equal to 8.0 micrograms/ml), followed by BMY 28142 (82%), carumonam (75%), and aztreonam (68%). The two monobactams exhibited no activity against gram-positive cocci at the concentrations tested, whereas BMY-28142 had excellent activity against nonenterococcal streptococci and good activity against staphylococci.

Antimicrobial activity of Ro 19-5247 (T-2525), a new oral cephalosporin, tested against 7,745 recent clinical isolates.

The susceptibility testing of 7,745 recent clinical isolates from four medical centers showed Ro 19-5247 to be eight- to greater than 64-fold more active than cephalexin against the Enterobacteriaceae. Ro 19-5247 was comparable with cephalexin in anti-staphylococcal activity (MIC50, 4.0 micrograms/ml) and fourfold more active than cefixime. None of the oral cephalosporins were effective (MIC50, greater than 32 micrograms/ml) against enterococci, Pseudomonas aeruginosa and P. maltophilia. beta-lactamase hydrolysis experiments failed to demonstrate significant Ro 19-5247 inactivation by ten commonly encountered chromosomal- or plasmid-mediated enzymes (P99, K1, K14, TEM, CARB, OXA).

CI-934, a new difluoroquinolone: in vitro antibacterial activity and proposed disk diffusion test interpretive criteria.

The susceptibility of 7,763 clinical isolates at four medical centers to CI-934 and three comparative quinolones was tested. CI-934 was the most active compound against Gram-positive isolates, such as staphylococci (MIC 90 = 0.25 microgram/ml), and enterococci (MIC 90 = 0.5 microgram/ml). CI-934 was the least active of these drugs against Pseudomonas spp. (MIC 90 = greater than 8.0 micrograms/ml). Against all other organisms CI-934 was very effective, being most comparable with enoxacin. With a selected group of isolates, CI-934 demonstrated high activity against Haemophilus influenzae (MIC 90 = 0.06 microgram/ml), Neisseria meningitidis and N. gonorrhoeae (MIC 90 = 0.13 microgram/ml), Listeria monocytogenes (MIC 90 = 1.0 microgram/ml), methicillin-resistant staphylococci (MIC 90 = 0.13 microgram/ml), and modest activity against anaerobes. Disk diffusion susceptibility testing of CI-934 was evaluated using 3-, 5-, and 10-micrograms disks. Because of its lower interpretive error rate, the 3-micrograms disk is tentatively recommended. With less than or equal to 2 micrograms/ml and greater than 4 micrograms/ml as the susceptible and resistant MIC breakpoints, the corresponding 3-micrograms disk zone diameters breakpoints are greater than or equal to 15 mm and less than or equal to 11 mm. Because most isolates of Pseudomonas spp. are not susceptible to CI-934 and the zone size interpretive error rate is particularly high (33%) with Pseudomonas spp., we suggest that isolates of this genus not be tested for clinical purposes.

In vitro activity of DJ-6783 (a keto carboxylic acid) compared with six other orally administered antimicrobial agents.

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.

RO 23-6240 (AM-833), a new fluoroquinolone: in vitro antimicrobial activity and tentative disk diffusion interpretive criteria.

The susceptibility of over 7000 recent clinical bacterial isolates to RO 23-6240, a new trifluorinated quinolone, was determined at four medical centers. Over 99% of Enterobacteriaceae and 97% of staphylococci were inhibited by less than or equal to 2.0 micrograms/ml of RO 23-6240. Only 71% of Pseudomonas spp. were inhibited by this concentration. Streptococci and enterococci were resistant to RO 23-6240. Clinical isolates of Haemophilus spp., pathogenic Neisseria spp., and Branhamella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of RO 23-6240. This drug's antibacterial activity was comparable with that of enoxacin and norfloxacin, but was less than that of ciprofloxacin against most species. Using less than or equal to 2.0 micrograms/ml and greater than or equal to 8.0 micrograms/ml as the susceptible and resistant MIC breakpoints for RO 23-6240, the regression analysis-derived disk diffusion zone diameter breakpoints for the 5 micrograms disk are: Susceptible greater than or equal to 19 mm intermediate 16-18 mm, and resistant less than or equal to 15 mm.

Quality control limits for microdilution susceptibility tests with aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid.

A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid). Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

A five-year multicenter study of the susceptibility of the Bacteroides fragilis group isolates to cephalosporins, cephamins, penicillins, clindamycin, and metronidazole in the United States.

Over 2800 clinical strains of the Bacteroides fragilis group were collected during a 5-year period from ten geographically separate sites and tested for their susceptibility to various antimicrobial agents using a broth microdilution method. Among the cephalosporins, ceftizoxime was the most active (13% resistance) and importantly exhibited relatively equal activity against both B. fragilis species and non-B. fragilis species. Cefotaxime exhibited similar activity with an overall resistance rate of 18%. Both ceftriaxone and cefoperazone were appreciably less active cephalosporins especially against non-B. fragilis species. With regard to cephamycins, cefoxitin (MIC90, 32 micrograms/ml) was more active than cefotetan (MIC90, > or = 256 micrograms/ml) and cefmetazole (MIC90, 64 micrograms/ml). Non-B. fragilis species were highly resistant to cefotetan and cefmetazole. Imipenem was highly active against all strains with the exception of four strains of B. fragilis. Ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam were all highly active with resistance rates < 2%. No resistance was detected to metronidazole, whereas 14% of isolates were resistant to clindamycin. When compared with other studies, these findings underscore the wide variability in susceptibility patterns reported nationwide and the need to continue monitoring these patterns to aid in choosing the most active compounds for therapy.

Drug therapy in otomycosis: an in vitro study.

Otomycosis represents a small percentage of clinical external otitis. This well documented entity is often a stubborn clinical problem and, in contrast to bacterial external otitis, there is no otic preparation with specific antifungal activity. In response to this lack of otic preparations, we have surveyed in vitro a variety of available preparations to determine the general spectrum of activity against appropriate bacterial and fungal species. An agar-disc diffusion system was used testing the drugs against (1.) bacteria common in external otitis, and (2.) a variety of yeast and filamentous fungi. Aqueous Merthiolate and Cresylate demonstrated good non-specific antimicrobial activity, while nystatin and clotrimazole demonstrated specific antifungal activity. Otic preparations can now be used which have demonstrated in vitro effectiveness and give an alternate means of therapy to the now empirically selected otic preparation used for otomycosis.